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Smoking Linked to More Genetic Havoc in MDS
The prospective National MDS Natural History Study evaluated 1898 patients with recently diagnosed or suspected MDS. An adjusted analysis linked higher number of pack-years to more mutations (P = .006), with those at the 90th percentile with 3.5 times the number of mutations as nonsmokers, researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting.
The findings “suggest that smoking potentially contributes to the multistep molecular genetic pathogenesis that ultimately results in diagnosis of the cancer,” said corresponding author Mikkael A. Sekeres, MD, of the Sylvester Comprehensive Cancer Center, University of Miami Health System in Florida, at a news briefing. “The more you smoke, the more likely you are to acquire more mutations and even develop a higher risk of myelodysplastic syndromes. [More smoking] was also associated with progression and survival.”
While numbers are uncertain, an estimated 10,000 or more people in the United States each year are diagnosed with MDS, also known as preleukemia, according to the American Cancer Society. Median survival ranges from 1 to 10.6 years based on risk group, although the cancer society says the statistics are dated and mainly from Europe.
Multiple studies have linked smoking to MDS. The new study aims to understand the possible effects of smoking on genetic mutations.
The research analyzed 1898 patients enrolled from 2016 to 2023 (52% who had ever smoked; 18% current smokers; mean smoking years, 29.8 ± 16.9 years). The patients had diagnoses of MDSs, MDS/myeloproliferative neoplasm overlap, or precursor conditions such as clonal cytopenia of undetermined significance (CCUS).
Smokers were more likely than nonsmokers to be men (68% vs 54%; P < .001) and aged 70-79 years (45% vs 34%; P < .001).
After adjustment for confounders, smokers had more average mutations linked to MDS than nonsmokers (2.0 vs 1.4; P = .04). Those at the 75th percentile of pack-years had 1.8 times as many MDS-linked mutations as nonsmokers.
The 5-year cumulative incidence of disease progression was higher in long-term smokers than in nonsmokers and those with shorter smoking history (mean proportion progressed, 20+ years vs < 20 years smoking/nonsmoking, 27% [19%-36%] vs 18% [13%-24%]; P < .05, respectively).
Also, overall survival was lower in smokers than in nonsmokers for patients with CCUS (hazard ratio [HR], 1.91; 95% CI, 1.03-3.55; P = .04) but not for those with MDS (HR, 1.21; 95% CI, 0.53-1.30; P = .41).
“The data suggests that a patient with a new diagnosis of MDS who also smokes should be counseled to stop smoking,” Sekeres said.
This may seem counterintuitive to patients, he acknowledged. When Sekeres was a medical student, he counseled a female patient with advanced lung cancer to quit smoking. “The patient looked at me like I had three heads and she said: ‘Why should I stop smoking? The cats are already out of the bag. I have lung cancer.’ ”
But the new study points to a possible benefit from quitting smoking while sick. “It appears that smoking contributes to the acquisition of new genetic mutations that can lead to worsening of the myelodysplastic syndromes and even evolution of the cancer into acute myeloid leukemia,” Sekeres said.
He added: “One thing to understand about these cancers of the bone marrow is they can take years or decades to develop. They’re not one-hit wonders. Smoking caused very specific genetic mutations. The cool part of this is that they’re the same genetic mutations smoking has been shown to cause in cancers like lung cancer, so we’re seeing consistency across cancers.”
Sekeres said he himself will counsel patients with MDS or acute myeloid leukemia to stop smoking. “If there’s anything we can do to intervene to prevent myelodysplastic syndrome from evolving into acute leukemia, my word, I sure I’m going to try it.”
In an interview, Peter Greenberg, MD, professor of medicine at Stanford Cancer Center in California, who’s familiar with the study but didn’t take part in the research, said the study suggests that smoking in MDS isn’t just related to exposure to fumes “but appears to be a much more widespread problem” related to its impact on generating hematologic stem cell mutations.
Most clinicians don’t warn patients with MDS about the dangers of smoking because they’re not aware of tobacco’s connection to the disease, Greenberg said. But there’s another reason to bring up smoking, he said: It boosts the risk for cardiovascular disease, which may be partially responsible for decreased survival in smokers.
Sekeres disclosed ties with Kurome, Schrödinger, and Bristol-Myers Squibb. Other authors reported multiple and various relationships with industry. Greenberg had no disclosures.
A version of this article appeared on Medscape.com.
The prospective National MDS Natural History Study evaluated 1898 patients with recently diagnosed or suspected MDS. An adjusted analysis linked higher number of pack-years to more mutations (P = .006), with those at the 90th percentile with 3.5 times the number of mutations as nonsmokers, researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting.
The findings “suggest that smoking potentially contributes to the multistep molecular genetic pathogenesis that ultimately results in diagnosis of the cancer,” said corresponding author Mikkael A. Sekeres, MD, of the Sylvester Comprehensive Cancer Center, University of Miami Health System in Florida, at a news briefing. “The more you smoke, the more likely you are to acquire more mutations and even develop a higher risk of myelodysplastic syndromes. [More smoking] was also associated with progression and survival.”
While numbers are uncertain, an estimated 10,000 or more people in the United States each year are diagnosed with MDS, also known as preleukemia, according to the American Cancer Society. Median survival ranges from 1 to 10.6 years based on risk group, although the cancer society says the statistics are dated and mainly from Europe.
Multiple studies have linked smoking to MDS. The new study aims to understand the possible effects of smoking on genetic mutations.
The research analyzed 1898 patients enrolled from 2016 to 2023 (52% who had ever smoked; 18% current smokers; mean smoking years, 29.8 ± 16.9 years). The patients had diagnoses of MDSs, MDS/myeloproliferative neoplasm overlap, or precursor conditions such as clonal cytopenia of undetermined significance (CCUS).
Smokers were more likely than nonsmokers to be men (68% vs 54%; P < .001) and aged 70-79 years (45% vs 34%; P < .001).
After adjustment for confounders, smokers had more average mutations linked to MDS than nonsmokers (2.0 vs 1.4; P = .04). Those at the 75th percentile of pack-years had 1.8 times as many MDS-linked mutations as nonsmokers.
The 5-year cumulative incidence of disease progression was higher in long-term smokers than in nonsmokers and those with shorter smoking history (mean proportion progressed, 20+ years vs < 20 years smoking/nonsmoking, 27% [19%-36%] vs 18% [13%-24%]; P < .05, respectively).
Also, overall survival was lower in smokers than in nonsmokers for patients with CCUS (hazard ratio [HR], 1.91; 95% CI, 1.03-3.55; P = .04) but not for those with MDS (HR, 1.21; 95% CI, 0.53-1.30; P = .41).
“The data suggests that a patient with a new diagnosis of MDS who also smokes should be counseled to stop smoking,” Sekeres said.
This may seem counterintuitive to patients, he acknowledged. When Sekeres was a medical student, he counseled a female patient with advanced lung cancer to quit smoking. “The patient looked at me like I had three heads and she said: ‘Why should I stop smoking? The cats are already out of the bag. I have lung cancer.’ ”
But the new study points to a possible benefit from quitting smoking while sick. “It appears that smoking contributes to the acquisition of new genetic mutations that can lead to worsening of the myelodysplastic syndromes and even evolution of the cancer into acute myeloid leukemia,” Sekeres said.
He added: “One thing to understand about these cancers of the bone marrow is they can take years or decades to develop. They’re not one-hit wonders. Smoking caused very specific genetic mutations. The cool part of this is that they’re the same genetic mutations smoking has been shown to cause in cancers like lung cancer, so we’re seeing consistency across cancers.”
Sekeres said he himself will counsel patients with MDS or acute myeloid leukemia to stop smoking. “If there’s anything we can do to intervene to prevent myelodysplastic syndrome from evolving into acute leukemia, my word, I sure I’m going to try it.”
In an interview, Peter Greenberg, MD, professor of medicine at Stanford Cancer Center in California, who’s familiar with the study but didn’t take part in the research, said the study suggests that smoking in MDS isn’t just related to exposure to fumes “but appears to be a much more widespread problem” related to its impact on generating hematologic stem cell mutations.
Most clinicians don’t warn patients with MDS about the dangers of smoking because they’re not aware of tobacco’s connection to the disease, Greenberg said. But there’s another reason to bring up smoking, he said: It boosts the risk for cardiovascular disease, which may be partially responsible for decreased survival in smokers.
Sekeres disclosed ties with Kurome, Schrödinger, and Bristol-Myers Squibb. Other authors reported multiple and various relationships with industry. Greenberg had no disclosures.
A version of this article appeared on Medscape.com.
The prospective National MDS Natural History Study evaluated 1898 patients with recently diagnosed or suspected MDS. An adjusted analysis linked higher number of pack-years to more mutations (P = .006), with those at the 90th percentile with 3.5 times the number of mutations as nonsmokers, researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting.
The findings “suggest that smoking potentially contributes to the multistep molecular genetic pathogenesis that ultimately results in diagnosis of the cancer,” said corresponding author Mikkael A. Sekeres, MD, of the Sylvester Comprehensive Cancer Center, University of Miami Health System in Florida, at a news briefing. “The more you smoke, the more likely you are to acquire more mutations and even develop a higher risk of myelodysplastic syndromes. [More smoking] was also associated with progression and survival.”
While numbers are uncertain, an estimated 10,000 or more people in the United States each year are diagnosed with MDS, also known as preleukemia, according to the American Cancer Society. Median survival ranges from 1 to 10.6 years based on risk group, although the cancer society says the statistics are dated and mainly from Europe.
Multiple studies have linked smoking to MDS. The new study aims to understand the possible effects of smoking on genetic mutations.
The research analyzed 1898 patients enrolled from 2016 to 2023 (52% who had ever smoked; 18% current smokers; mean smoking years, 29.8 ± 16.9 years). The patients had diagnoses of MDSs, MDS/myeloproliferative neoplasm overlap, or precursor conditions such as clonal cytopenia of undetermined significance (CCUS).
Smokers were more likely than nonsmokers to be men (68% vs 54%; P < .001) and aged 70-79 years (45% vs 34%; P < .001).
After adjustment for confounders, smokers had more average mutations linked to MDS than nonsmokers (2.0 vs 1.4; P = .04). Those at the 75th percentile of pack-years had 1.8 times as many MDS-linked mutations as nonsmokers.
The 5-year cumulative incidence of disease progression was higher in long-term smokers than in nonsmokers and those with shorter smoking history (mean proportion progressed, 20+ years vs < 20 years smoking/nonsmoking, 27% [19%-36%] vs 18% [13%-24%]; P < .05, respectively).
Also, overall survival was lower in smokers than in nonsmokers for patients with CCUS (hazard ratio [HR], 1.91; 95% CI, 1.03-3.55; P = .04) but not for those with MDS (HR, 1.21; 95% CI, 0.53-1.30; P = .41).
“The data suggests that a patient with a new diagnosis of MDS who also smokes should be counseled to stop smoking,” Sekeres said.
This may seem counterintuitive to patients, he acknowledged. When Sekeres was a medical student, he counseled a female patient with advanced lung cancer to quit smoking. “The patient looked at me like I had three heads and she said: ‘Why should I stop smoking? The cats are already out of the bag. I have lung cancer.’ ”
But the new study points to a possible benefit from quitting smoking while sick. “It appears that smoking contributes to the acquisition of new genetic mutations that can lead to worsening of the myelodysplastic syndromes and even evolution of the cancer into acute myeloid leukemia,” Sekeres said.
He added: “One thing to understand about these cancers of the bone marrow is they can take years or decades to develop. They’re not one-hit wonders. Smoking caused very specific genetic mutations. The cool part of this is that they’re the same genetic mutations smoking has been shown to cause in cancers like lung cancer, so we’re seeing consistency across cancers.”
Sekeres said he himself will counsel patients with MDS or acute myeloid leukemia to stop smoking. “If there’s anything we can do to intervene to prevent myelodysplastic syndrome from evolving into acute leukemia, my word, I sure I’m going to try it.”
In an interview, Peter Greenberg, MD, professor of medicine at Stanford Cancer Center in California, who’s familiar with the study but didn’t take part in the research, said the study suggests that smoking in MDS isn’t just related to exposure to fumes “but appears to be a much more widespread problem” related to its impact on generating hematologic stem cell mutations.
Most clinicians don’t warn patients with MDS about the dangers of smoking because they’re not aware of tobacco’s connection to the disease, Greenberg said. But there’s another reason to bring up smoking, he said: It boosts the risk for cardiovascular disease, which may be partially responsible for decreased survival in smokers.
Sekeres disclosed ties with Kurome, Schrödinger, and Bristol-Myers Squibb. Other authors reported multiple and various relationships with industry. Greenberg had no disclosures.
A version of this article appeared on Medscape.com.
FROM ASH 2024
Fertility Preservation in SCD: Women Have More Complications
Of 46 patients with SCD, complications occurred in 25 of 55 controlled ovarian hyperstimulation cycles, including 29 vaso-occlusive episodes (VOEs), researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting.
Of 21 post-retrieval VOEs, 19 required emergency department care or hospitalization.
“Baseline sickle cell disease severity is most likely associated with a patient’s risk of complications from an egg retrieval cycle,” study co-author Sarah Cromack, MD, a reproductive endocrinology and infertility fellow at Northwestern University, Chicago, said in an interview.
“Both hematologists and reproductive endocrinologists can use this information to plan ahead and anticipate possible issues, check blood counts prior to and after egg retrieval to see if transfusion is needed, and plan close follow-up during stimulation and immediately after egg retrieval to evaluate and treat pain.”
SCD Accelerates Decline in Ovarian Reserve
Pediatric hematologist Lydia H. Pecker, MD, MS, of Johns Hopkins University School of Medicine, Baltimore, the study’s corresponding author, said in an interview that SCD is “a disease of accelerated aging” that leads to accelerated decline in ovarian reserve. “The common indication for fertility preservation in SCD is before bone marrow transplant or gene therapy,” she said, although FP can also be offered to other patients with SCD.
According to Cromack, researchers launched the study to expand information about SCD and FP in light of sparse data about outcomes.
All the 46 patients had hemoglobin SS (HbSS, 93%) and HbSβ0-thalassemia (7%) and a median age of 23.7 (18-28) years. Almost all (44 patients) underwent FP prior to curative treatments, and all had at least one SCD-related complication, mainly cerebrovascular disease (16), acute chest syndrome (23), and more than two VOEs per year (31).
Median anti-Mullerian hormone (AMH) level (2.1 ng/mL), a measurement of ovarian reserve, was lower than the expected level of 2.8-3.4 ng/mL among women in the age range of the patients, the researchers reported. “This is consistent with previous studies showing lower AMH for age in women with sickle cell disease,” Pecker said.
Complications in 45% of Retrieval Cycles
“In terms of success of oocyte cryopreservation, the median number of mature eggs frozen was 11,” said co-author and reproductive endocrinologist Jessica Walter, MD, of Northwestern University, in an interview. “Given the average age of 24 years in the cohort, this would give each patient about a 70% estimated probability of at least one live birth from their cohort of frozen eggs. Thus, patients hoping for more than one child may want to consider more than one cycle of egg freezing.”
The rate of complications was “fairly high” at 45% of all cycles, Walter said. “These were mostly complications from underlying sickle cell disease, including unplanned transfusions and admissions for vaso-occlusive crises. Surprisingly, there were very few cases of ovarian hyperstimulation syndrome in this young patient group, which may be due to a combination of underlying vascular disease, lower peak estradiol levels, and slightly less eggs retrieved then would be expected compared to an age-matched healthy controls.”
Any FP complication was associated with more than three VOEs in the year before controlled ovarian hyperstimulation (mean of three VOEs per patient without complications vs six per patient with complications; P = .036).
Higher Than Normal Need for Multiple Cycles
Reproductive endocrinologist H. Irene Su, MD, professor and co-director of the Center for OB/GYN Research Innovations at Moores Cancer Center, University of California San Diego, praised the study as “an important report” in an interview.
Su, who wasn’t involved in the research, said the percentage of patients requiring more than one cycle due to cancellation or low oocyte yield — 13% — is “higher than expected, given the young age of this cohort.”
This could reflect the hypothesis that “sickle cell crises and hypoxia adversely affect the finite number of oocytes in the ovary,” she said.
As for the study findings regarding complications, she said the rate “is very high compared to the general infertility or fertility preservation population. It would be good to learn predictors of these outcomes so that fertility and hematology clinicians can work together to stratify risk and supportive services around FP cycles. It would also be good to know if the post-retrieval VOE were unexpected given the patient’s disease activity prior to FP.”
Message: FP in SCD Is Feasible, Acceptable
A.D. Mishkin, MD, MPH, associate professor of psychiatry and liaison to the Blood and Marrow Transplantation Program at NewYork–Presbyterian/Columbia University Irving Medical Center, New York City, said in an interview that the study “establishes the feasibility and acceptability of oocyte harvest and preservation in a population of patients with active ongoing symptoms from SCD. It also indicates their interest in pursuing fertility preservation in the setting of frequent crises and the potential for management of ensuing complications.”
Mishkin, who didn’t take part in the research, highlighted the finding that half the patients got access to FP via public insurance or research funding. “Even in this population where most women had multiple complications in the year prior to FP, and even among patients who needed multiple retrievals, these patients wanted to go through that risk to preserve their fertility,” Mishkin said. “This is an important finding given the very limited access many individuals have to FP due to its high cost and limited insurance coverage, which is also largely state-dependent.”
There’s another factor to consider regarding SCD and FP: The potential danger of pregnancy.
Corresponding author Pecker noted that “pregnancy is high risk for people with sickle cell disease. There are very high rates of severe maternal mortality and morbidity even in high-income countries. However, some of this is modifiable with routine use of chronic transfusions during pregnancy and with high-quality and integrated expert SCD and expert maternal fetal medicine care during pregnancy.”
The National Institutes of Health supported the research. Pecker reported receiving research funding from Alexion, Novartis, and Aummune and consulting for Novo Nordisk. Other authors reported no disclosures. Su and Mishkin reported no disclosures.
A version of this article appeared on Medscape.com.
Of 46 patients with SCD, complications occurred in 25 of 55 controlled ovarian hyperstimulation cycles, including 29 vaso-occlusive episodes (VOEs), researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting.
Of 21 post-retrieval VOEs, 19 required emergency department care or hospitalization.
“Baseline sickle cell disease severity is most likely associated with a patient’s risk of complications from an egg retrieval cycle,” study co-author Sarah Cromack, MD, a reproductive endocrinology and infertility fellow at Northwestern University, Chicago, said in an interview.
“Both hematologists and reproductive endocrinologists can use this information to plan ahead and anticipate possible issues, check blood counts prior to and after egg retrieval to see if transfusion is needed, and plan close follow-up during stimulation and immediately after egg retrieval to evaluate and treat pain.”
SCD Accelerates Decline in Ovarian Reserve
Pediatric hematologist Lydia H. Pecker, MD, MS, of Johns Hopkins University School of Medicine, Baltimore, the study’s corresponding author, said in an interview that SCD is “a disease of accelerated aging” that leads to accelerated decline in ovarian reserve. “The common indication for fertility preservation in SCD is before bone marrow transplant or gene therapy,” she said, although FP can also be offered to other patients with SCD.
According to Cromack, researchers launched the study to expand information about SCD and FP in light of sparse data about outcomes.
All the 46 patients had hemoglobin SS (HbSS, 93%) and HbSβ0-thalassemia (7%) and a median age of 23.7 (18-28) years. Almost all (44 patients) underwent FP prior to curative treatments, and all had at least one SCD-related complication, mainly cerebrovascular disease (16), acute chest syndrome (23), and more than two VOEs per year (31).
Median anti-Mullerian hormone (AMH) level (2.1 ng/mL), a measurement of ovarian reserve, was lower than the expected level of 2.8-3.4 ng/mL among women in the age range of the patients, the researchers reported. “This is consistent with previous studies showing lower AMH for age in women with sickle cell disease,” Pecker said.
Complications in 45% of Retrieval Cycles
“In terms of success of oocyte cryopreservation, the median number of mature eggs frozen was 11,” said co-author and reproductive endocrinologist Jessica Walter, MD, of Northwestern University, in an interview. “Given the average age of 24 years in the cohort, this would give each patient about a 70% estimated probability of at least one live birth from their cohort of frozen eggs. Thus, patients hoping for more than one child may want to consider more than one cycle of egg freezing.”
The rate of complications was “fairly high” at 45% of all cycles, Walter said. “These were mostly complications from underlying sickle cell disease, including unplanned transfusions and admissions for vaso-occlusive crises. Surprisingly, there were very few cases of ovarian hyperstimulation syndrome in this young patient group, which may be due to a combination of underlying vascular disease, lower peak estradiol levels, and slightly less eggs retrieved then would be expected compared to an age-matched healthy controls.”
Any FP complication was associated with more than three VOEs in the year before controlled ovarian hyperstimulation (mean of three VOEs per patient without complications vs six per patient with complications; P = .036).
Higher Than Normal Need for Multiple Cycles
Reproductive endocrinologist H. Irene Su, MD, professor and co-director of the Center for OB/GYN Research Innovations at Moores Cancer Center, University of California San Diego, praised the study as “an important report” in an interview.
Su, who wasn’t involved in the research, said the percentage of patients requiring more than one cycle due to cancellation or low oocyte yield — 13% — is “higher than expected, given the young age of this cohort.”
This could reflect the hypothesis that “sickle cell crises and hypoxia adversely affect the finite number of oocytes in the ovary,” she said.
As for the study findings regarding complications, she said the rate “is very high compared to the general infertility or fertility preservation population. It would be good to learn predictors of these outcomes so that fertility and hematology clinicians can work together to stratify risk and supportive services around FP cycles. It would also be good to know if the post-retrieval VOE were unexpected given the patient’s disease activity prior to FP.”
Message: FP in SCD Is Feasible, Acceptable
A.D. Mishkin, MD, MPH, associate professor of psychiatry and liaison to the Blood and Marrow Transplantation Program at NewYork–Presbyterian/Columbia University Irving Medical Center, New York City, said in an interview that the study “establishes the feasibility and acceptability of oocyte harvest and preservation in a population of patients with active ongoing symptoms from SCD. It also indicates their interest in pursuing fertility preservation in the setting of frequent crises and the potential for management of ensuing complications.”
Mishkin, who didn’t take part in the research, highlighted the finding that half the patients got access to FP via public insurance or research funding. “Even in this population where most women had multiple complications in the year prior to FP, and even among patients who needed multiple retrievals, these patients wanted to go through that risk to preserve their fertility,” Mishkin said. “This is an important finding given the very limited access many individuals have to FP due to its high cost and limited insurance coverage, which is also largely state-dependent.”
There’s another factor to consider regarding SCD and FP: The potential danger of pregnancy.
Corresponding author Pecker noted that “pregnancy is high risk for people with sickle cell disease. There are very high rates of severe maternal mortality and morbidity even in high-income countries. However, some of this is modifiable with routine use of chronic transfusions during pregnancy and with high-quality and integrated expert SCD and expert maternal fetal medicine care during pregnancy.”
The National Institutes of Health supported the research. Pecker reported receiving research funding from Alexion, Novartis, and Aummune and consulting for Novo Nordisk. Other authors reported no disclosures. Su and Mishkin reported no disclosures.
A version of this article appeared on Medscape.com.
Of 46 patients with SCD, complications occurred in 25 of 55 controlled ovarian hyperstimulation cycles, including 29 vaso-occlusive episodes (VOEs), researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting.
Of 21 post-retrieval VOEs, 19 required emergency department care or hospitalization.
“Baseline sickle cell disease severity is most likely associated with a patient’s risk of complications from an egg retrieval cycle,” study co-author Sarah Cromack, MD, a reproductive endocrinology and infertility fellow at Northwestern University, Chicago, said in an interview.
“Both hematologists and reproductive endocrinologists can use this information to plan ahead and anticipate possible issues, check blood counts prior to and after egg retrieval to see if transfusion is needed, and plan close follow-up during stimulation and immediately after egg retrieval to evaluate and treat pain.”
SCD Accelerates Decline in Ovarian Reserve
Pediatric hematologist Lydia H. Pecker, MD, MS, of Johns Hopkins University School of Medicine, Baltimore, the study’s corresponding author, said in an interview that SCD is “a disease of accelerated aging” that leads to accelerated decline in ovarian reserve. “The common indication for fertility preservation in SCD is before bone marrow transplant or gene therapy,” she said, although FP can also be offered to other patients with SCD.
According to Cromack, researchers launched the study to expand information about SCD and FP in light of sparse data about outcomes.
All the 46 patients had hemoglobin SS (HbSS, 93%) and HbSβ0-thalassemia (7%) and a median age of 23.7 (18-28) years. Almost all (44 patients) underwent FP prior to curative treatments, and all had at least one SCD-related complication, mainly cerebrovascular disease (16), acute chest syndrome (23), and more than two VOEs per year (31).
Median anti-Mullerian hormone (AMH) level (2.1 ng/mL), a measurement of ovarian reserve, was lower than the expected level of 2.8-3.4 ng/mL among women in the age range of the patients, the researchers reported. “This is consistent with previous studies showing lower AMH for age in women with sickle cell disease,” Pecker said.
Complications in 45% of Retrieval Cycles
“In terms of success of oocyte cryopreservation, the median number of mature eggs frozen was 11,” said co-author and reproductive endocrinologist Jessica Walter, MD, of Northwestern University, in an interview. “Given the average age of 24 years in the cohort, this would give each patient about a 70% estimated probability of at least one live birth from their cohort of frozen eggs. Thus, patients hoping for more than one child may want to consider more than one cycle of egg freezing.”
The rate of complications was “fairly high” at 45% of all cycles, Walter said. “These were mostly complications from underlying sickle cell disease, including unplanned transfusions and admissions for vaso-occlusive crises. Surprisingly, there were very few cases of ovarian hyperstimulation syndrome in this young patient group, which may be due to a combination of underlying vascular disease, lower peak estradiol levels, and slightly less eggs retrieved then would be expected compared to an age-matched healthy controls.”
Any FP complication was associated with more than three VOEs in the year before controlled ovarian hyperstimulation (mean of three VOEs per patient without complications vs six per patient with complications; P = .036).
Higher Than Normal Need for Multiple Cycles
Reproductive endocrinologist H. Irene Su, MD, professor and co-director of the Center for OB/GYN Research Innovations at Moores Cancer Center, University of California San Diego, praised the study as “an important report” in an interview.
Su, who wasn’t involved in the research, said the percentage of patients requiring more than one cycle due to cancellation or low oocyte yield — 13% — is “higher than expected, given the young age of this cohort.”
This could reflect the hypothesis that “sickle cell crises and hypoxia adversely affect the finite number of oocytes in the ovary,” she said.
As for the study findings regarding complications, she said the rate “is very high compared to the general infertility or fertility preservation population. It would be good to learn predictors of these outcomes so that fertility and hematology clinicians can work together to stratify risk and supportive services around FP cycles. It would also be good to know if the post-retrieval VOE were unexpected given the patient’s disease activity prior to FP.”
Message: FP in SCD Is Feasible, Acceptable
A.D. Mishkin, MD, MPH, associate professor of psychiatry and liaison to the Blood and Marrow Transplantation Program at NewYork–Presbyterian/Columbia University Irving Medical Center, New York City, said in an interview that the study “establishes the feasibility and acceptability of oocyte harvest and preservation in a population of patients with active ongoing symptoms from SCD. It also indicates their interest in pursuing fertility preservation in the setting of frequent crises and the potential for management of ensuing complications.”
Mishkin, who didn’t take part in the research, highlighted the finding that half the patients got access to FP via public insurance or research funding. “Even in this population where most women had multiple complications in the year prior to FP, and even among patients who needed multiple retrievals, these patients wanted to go through that risk to preserve their fertility,” Mishkin said. “This is an important finding given the very limited access many individuals have to FP due to its high cost and limited insurance coverage, which is also largely state-dependent.”
There’s another factor to consider regarding SCD and FP: The potential danger of pregnancy.
Corresponding author Pecker noted that “pregnancy is high risk for people with sickle cell disease. There are very high rates of severe maternal mortality and morbidity even in high-income countries. However, some of this is modifiable with routine use of chronic transfusions during pregnancy and with high-quality and integrated expert SCD and expert maternal fetal medicine care during pregnancy.”
The National Institutes of Health supported the research. Pecker reported receiving research funding from Alexion, Novartis, and Aummune and consulting for Novo Nordisk. Other authors reported no disclosures. Su and Mishkin reported no disclosures.
A version of this article appeared on Medscape.com.
FROM ASH 2024
With Chemo, Blinatumomab Boosts DFS in Pediatric B-ALL
Among pediatric patients with B-ALL followed for a mean of 2.5 years (1.6-3.2 years), 718 patients in the blinatumomab-plus-chemotherapy group had a 3-year DFS of 96.0 ± 1.2%, compared with 87.9 ± 2.1% of the 722 patients in the chemotherapy-only group, researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting.
“Our results demonstrate that blinatumomab added to chemotherapy represents a new treatment standard for most patients with NCI [National Cancer Institute] standard-risk [B-ALL],” said first author Rachel E. Rau, MD, Seattle Children’s Hospital, University of Washington, during a news briefing.
As Cynthia E. Dunbar, MD, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute, noted in a news briefing: “B-cell ALL is the most common childhood cancer and one of the most treatable. However, some children still relapse following standard chemotherapy treatments and then have a much grimmer outcome.”
The AALL1731 study was initiated in 2019 with a recruitment goal of 2245 participants. The patients were over age 1 and less than 10 years, with an initial white blood cell count of < 50,000/μL and were considered to be standard risk–high or standard risk–average.
The control group received standard-intensity chemotherapy (standard risk–average patients) or augmented Berlin-Frankfurt-Münster–based chemotherapy (standard risk–high patients). In addition, the blinatumomab groups received two cycles of the drug.
Randomization was terminated in 2024 at 1440 patients because of the positive results. Patients had a median age of 4.3 years (2.8-6.4), 52.6% were boys, 26% were Hispanic, and 5% were non-Hispanic Black.
The addition of blinatumomab improved DFS by 61% (hazard ratio, 0.39; 95% CI, 0.24-0.64; P < .0001).
In the group of standard risk–average patients, 3-year DFS was 97.5±1.3% in the blinatumomab group vs 90.2±2.3% in the control group (HR, 0.33; 95% CI, 0.15-0.69). For standard risk–high patients, 3-year DFS was 94.1 ± 2.5% and 84.8 ± 3.8%, respectively.
Six deaths occurred in remission, all in standard risk–high patients and none during blinatumomab cycles. Out of first courses of blinatumomab, 0.3% were associated with Grade 3 or higher cytokine release syndrome and 0.7% with seizures.
“We did note higher rates of subsequent sepsis and catheter-related infections in our standard risk–average patients who received blinatumomab,” Rau said.
“The improvement in disease survival was secondary to significant reduction in bone marrow relapse,” Rau added. “We did not see a similar reduction in the more rare event of an isolated central nervous system relapse. This finding was not surprising given blinatumomab’s known limited activity in the central nervous system.”
Rau noted that there are two challenges in terms of access to blinatumomab: its cost, at about $225,000 per a 2023 report, and its administration. The drug is administered via 4-week-long infusions. “The delivery method is very cumbersome,” she said.
“These are big problems that are going to take the combined efforts of pediatric oncologist cancer consortia and pharmaceutical industry partners as well as government agencies,” she said. Fortunately, she said, in June 2024 the Food and Drug Administration approved blinatumomab for adult and pediatric patients 1 month and older with CD19-positive Philadelphia chromosome–negative B-ALL in the consolidation phase of multiphase chemotherapy.
“So it’s relatively easy, at least, to prescribe blinatumomab in the United States for our patients that we feel would benefit from it,” she said.
As for method of delivery, Rau said easier-to-deliver formulations are in development.
Rau has disclosed spousal employment (AbbVie), serving on advisory boards (Servier, Jazz), consulting, and receiving honoraria (Jazz). Other study authors report various disclosures including ties with Amgen, the maker of blinatumomab. Dunbar has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Among pediatric patients with B-ALL followed for a mean of 2.5 years (1.6-3.2 years), 718 patients in the blinatumomab-plus-chemotherapy group had a 3-year DFS of 96.0 ± 1.2%, compared with 87.9 ± 2.1% of the 722 patients in the chemotherapy-only group, researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting.
“Our results demonstrate that blinatumomab added to chemotherapy represents a new treatment standard for most patients with NCI [National Cancer Institute] standard-risk [B-ALL],” said first author Rachel E. Rau, MD, Seattle Children’s Hospital, University of Washington, during a news briefing.
As Cynthia E. Dunbar, MD, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute, noted in a news briefing: “B-cell ALL is the most common childhood cancer and one of the most treatable. However, some children still relapse following standard chemotherapy treatments and then have a much grimmer outcome.”
The AALL1731 study was initiated in 2019 with a recruitment goal of 2245 participants. The patients were over age 1 and less than 10 years, with an initial white blood cell count of < 50,000/μL and were considered to be standard risk–high or standard risk–average.
The control group received standard-intensity chemotherapy (standard risk–average patients) or augmented Berlin-Frankfurt-Münster–based chemotherapy (standard risk–high patients). In addition, the blinatumomab groups received two cycles of the drug.
Randomization was terminated in 2024 at 1440 patients because of the positive results. Patients had a median age of 4.3 years (2.8-6.4), 52.6% were boys, 26% were Hispanic, and 5% were non-Hispanic Black.
The addition of blinatumomab improved DFS by 61% (hazard ratio, 0.39; 95% CI, 0.24-0.64; P < .0001).
In the group of standard risk–average patients, 3-year DFS was 97.5±1.3% in the blinatumomab group vs 90.2±2.3% in the control group (HR, 0.33; 95% CI, 0.15-0.69). For standard risk–high patients, 3-year DFS was 94.1 ± 2.5% and 84.8 ± 3.8%, respectively.
Six deaths occurred in remission, all in standard risk–high patients and none during blinatumomab cycles. Out of first courses of blinatumomab, 0.3% were associated with Grade 3 or higher cytokine release syndrome and 0.7% with seizures.
“We did note higher rates of subsequent sepsis and catheter-related infections in our standard risk–average patients who received blinatumomab,” Rau said.
“The improvement in disease survival was secondary to significant reduction in bone marrow relapse,” Rau added. “We did not see a similar reduction in the more rare event of an isolated central nervous system relapse. This finding was not surprising given blinatumomab’s known limited activity in the central nervous system.”
Rau noted that there are two challenges in terms of access to blinatumomab: its cost, at about $225,000 per a 2023 report, and its administration. The drug is administered via 4-week-long infusions. “The delivery method is very cumbersome,” she said.
“These are big problems that are going to take the combined efforts of pediatric oncologist cancer consortia and pharmaceutical industry partners as well as government agencies,” she said. Fortunately, she said, in June 2024 the Food and Drug Administration approved blinatumomab for adult and pediatric patients 1 month and older with CD19-positive Philadelphia chromosome–negative B-ALL in the consolidation phase of multiphase chemotherapy.
“So it’s relatively easy, at least, to prescribe blinatumomab in the United States for our patients that we feel would benefit from it,” she said.
As for method of delivery, Rau said easier-to-deliver formulations are in development.
Rau has disclosed spousal employment (AbbVie), serving on advisory boards (Servier, Jazz), consulting, and receiving honoraria (Jazz). Other study authors report various disclosures including ties with Amgen, the maker of blinatumomab. Dunbar has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Among pediatric patients with B-ALL followed for a mean of 2.5 years (1.6-3.2 years), 718 patients in the blinatumomab-plus-chemotherapy group had a 3-year DFS of 96.0 ± 1.2%, compared with 87.9 ± 2.1% of the 722 patients in the chemotherapy-only group, researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting.
“Our results demonstrate that blinatumomab added to chemotherapy represents a new treatment standard for most patients with NCI [National Cancer Institute] standard-risk [B-ALL],” said first author Rachel E. Rau, MD, Seattle Children’s Hospital, University of Washington, during a news briefing.
As Cynthia E. Dunbar, MD, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute, noted in a news briefing: “B-cell ALL is the most common childhood cancer and one of the most treatable. However, some children still relapse following standard chemotherapy treatments and then have a much grimmer outcome.”
The AALL1731 study was initiated in 2019 with a recruitment goal of 2245 participants. The patients were over age 1 and less than 10 years, with an initial white blood cell count of < 50,000/μL and were considered to be standard risk–high or standard risk–average.
The control group received standard-intensity chemotherapy (standard risk–average patients) or augmented Berlin-Frankfurt-Münster–based chemotherapy (standard risk–high patients). In addition, the blinatumomab groups received two cycles of the drug.
Randomization was terminated in 2024 at 1440 patients because of the positive results. Patients had a median age of 4.3 years (2.8-6.4), 52.6% were boys, 26% were Hispanic, and 5% were non-Hispanic Black.
The addition of blinatumomab improved DFS by 61% (hazard ratio, 0.39; 95% CI, 0.24-0.64; P < .0001).
In the group of standard risk–average patients, 3-year DFS was 97.5±1.3% in the blinatumomab group vs 90.2±2.3% in the control group (HR, 0.33; 95% CI, 0.15-0.69). For standard risk–high patients, 3-year DFS was 94.1 ± 2.5% and 84.8 ± 3.8%, respectively.
Six deaths occurred in remission, all in standard risk–high patients and none during blinatumomab cycles. Out of first courses of blinatumomab, 0.3% were associated with Grade 3 or higher cytokine release syndrome and 0.7% with seizures.
“We did note higher rates of subsequent sepsis and catheter-related infections in our standard risk–average patients who received blinatumomab,” Rau said.
“The improvement in disease survival was secondary to significant reduction in bone marrow relapse,” Rau added. “We did not see a similar reduction in the more rare event of an isolated central nervous system relapse. This finding was not surprising given blinatumomab’s known limited activity in the central nervous system.”
Rau noted that there are two challenges in terms of access to blinatumomab: its cost, at about $225,000 per a 2023 report, and its administration. The drug is administered via 4-week-long infusions. “The delivery method is very cumbersome,” she said.
“These are big problems that are going to take the combined efforts of pediatric oncologist cancer consortia and pharmaceutical industry partners as well as government agencies,” she said. Fortunately, she said, in June 2024 the Food and Drug Administration approved blinatumomab for adult and pediatric patients 1 month and older with CD19-positive Philadelphia chromosome–negative B-ALL in the consolidation phase of multiphase chemotherapy.
“So it’s relatively easy, at least, to prescribe blinatumomab in the United States for our patients that we feel would benefit from it,” she said.
As for method of delivery, Rau said easier-to-deliver formulations are in development.
Rau has disclosed spousal employment (AbbVie), serving on advisory boards (Servier, Jazz), consulting, and receiving honoraria (Jazz). Other study authors report various disclosures including ties with Amgen, the maker of blinatumomab. Dunbar has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ASH 2024
LBCL: Bispecific Antibodies Fare Less Well in Real-World Analysis
In a presentation at the American Society of Hematology (ASH) 2024 Annual Meeting, researchers reported that of 172 patients treated with the drugs who had evaluable responses over a median follow-up of 5 months, median progression-free survival was 2.7 months (95% CI, 2.0-3.9) and median overall survival was 7.2 months (95% CI, 6.1–not reached).
It’s important to consider the real-world nature of the study’s patient population, said first author Taylor R. Brooks, MD, of Cleveland Clinic, Ohio, in an interview. “Compared to pivotal trials, our cohort was enriched for patients with high-risk features, with almost three quarters having some comorbidity that would’ve excluded them from one of the [earlier] studies.”
He added that “though individuals eligible to receive these medicines may be more sick with high-risk disease, a sizable fraction will respond, and some will maintain remissions.’”
According to Brooks, about one third of patients with diffuse LBCL relapse after standard front-line R-CHOP therapy. “The prognosis is poor for patients who are not candidates for aggressive salvage chemotherapy and for those who relapse after two or more lines,” Brooks said. “T cell–engaging bispecific antibodies have emerged as a promising option for patients with relapsed or refractory large B-cell lymphoma, given their favorable rates and duration of responses as well as their manageable rates of toxicities.”
The Food and Drug Administration (FDA) granted accelerated approval for epcoritamab and glofitamab in 2023.
“With increasing uptake into clinical practice following the FDA approvals, there is increasing interest in assessing the efficacy and safety of these drugs in real-world, nontrial settings,” Brooks said. “The goal of our study was to investigate outcomes and identify clinical factors associated with outcomes.”
The multicenter, retrospective, observational REALBiTE study tracked 209 patients with relapsed/refractory diffuse LBCL at 19 US centers (epcoritamab, n = 139; glofitamab, n = 70; median age at start of treatment, 67 years [58-76]; 62.2% male; 74.2% diffuse LBCL). The median number of lines of therapy was three (range, 1-12).
“Patients who received epcoritamab tended to be slightly older, were more likely to have a history of indolent non-Hodgkin lymphoma prior to their diagnosis of aggressive B-cell lymphoma and were more likely to have an elevated International Prognostic Index score at the start of bispecific therapy, suggesting that these patients may have been slightly older with higher-risk disease compared to those who received glofitamab,” Brooks said.
In total, 172 patients were response-evaluable. The overall response rate was 50.6% (complete response, 23.8%; partial response, 26.7%; stable disease, 5.8%; progressive disease, 43.6%).
The overall and complete response rates were “somewhat lower that what has been published in the pivotal trials of these medicines,” Brooks said. The low progression-free and overall survival rates “highlight the difficulty in managing this group of patients.”
Cytokine release syndrome (CRS) of any grade occurred in 39.2% of patients: 51% in the epcoritamab group and 28.6% in the glofitamab group. Grade ≥3 CRS occurred in 4.3% of patients, who were all taking epcoritamab.
“For epcoritamab, CRS was almost entirely of low grade, and most CRS events occurred around administration of the first full dose of the drug on day 15,” Brooks said. “Similarly, the CRS events for glofitamab were mostly of low grade, though events were observed to occur throughout the step-up dosing. Tocilizumab was administered in about one fifth of the patients.”
In addition, Brooks said, “we found that, among the 19 individuals with paired biopsy samples before and after bispecific therapy, nearly all — 89% — were found to have lost CD20 expression. We expected some patients to experience loss of this important target, but the rate at which we found this to be the case was surprisingly high.”
Brooks added that “clinicians should be acquainted with CRS, ICANS [immune effector cell-associated neurotoxicity syndrome], and mitigation strategies if they are prescribing these medicines. Appropriate and timely management using tocilizumab, steroids, and other adjunctive measures can effectively manage these complications and hopefully allow for the continued delivery of therapy.”
In an interview, Matthew Lunning, DO, associate professor at the University of Nebraska Medical Center/Fred & Pamela Buffett Cancer Center, Omaha, who didn’t take part in the new study, said the findings aren’t bad news. Instead, they’re “practical news,” because they offer insight into how the drugs work.
“The big lesson from this and other trials is the importance of assessing for CD20 expression prior to taking a bispecific off the shelf, “ he said. “These are learnings that often come after approval.”
He added that it’s clear that, “in more heavily pretreated patients, more disease led to less optimal results and higher risk for toxicities.”
Lunning also noted that both epcoritamab and glofitamab “entered into a crowded and chaotic relapsed/refractory LBCL space based high complete response rates with the opportunity for durability in those complete responses.”
Academic institutions were especially interested, as they can manage CRS and ICANS, but “significantly less enthusiasm has been seen in community practices that expect CRS/ICANS to be in the rear-view mirror if they are going to deliver any bispecific,” he said. “It is not that they don’t have the clinical acumen to manage CRS/ICANS. I believe it is the perception of the lack of supportive infrastructure necessary to manage these toxicities.”
There was no study funding. Brooks has reported no disclosures. Other authors have reported various disclosures including relationships with Novartis, AbbVie, Genentech, Genmab, Biogen, Amgen, and others. Lunning has disclosed ties with AbbVie, Genmab, Kite, Bristol-Myers Squibb, Regeneron, and ADC Therapeutics.
A version of this article first appeared on Medscape.com.
In a presentation at the American Society of Hematology (ASH) 2024 Annual Meeting, researchers reported that of 172 patients treated with the drugs who had evaluable responses over a median follow-up of 5 months, median progression-free survival was 2.7 months (95% CI, 2.0-3.9) and median overall survival was 7.2 months (95% CI, 6.1–not reached).
It’s important to consider the real-world nature of the study’s patient population, said first author Taylor R. Brooks, MD, of Cleveland Clinic, Ohio, in an interview. “Compared to pivotal trials, our cohort was enriched for patients with high-risk features, with almost three quarters having some comorbidity that would’ve excluded them from one of the [earlier] studies.”
He added that “though individuals eligible to receive these medicines may be more sick with high-risk disease, a sizable fraction will respond, and some will maintain remissions.’”
According to Brooks, about one third of patients with diffuse LBCL relapse after standard front-line R-CHOP therapy. “The prognosis is poor for patients who are not candidates for aggressive salvage chemotherapy and for those who relapse after two or more lines,” Brooks said. “T cell–engaging bispecific antibodies have emerged as a promising option for patients with relapsed or refractory large B-cell lymphoma, given their favorable rates and duration of responses as well as their manageable rates of toxicities.”
The Food and Drug Administration (FDA) granted accelerated approval for epcoritamab and glofitamab in 2023.
“With increasing uptake into clinical practice following the FDA approvals, there is increasing interest in assessing the efficacy and safety of these drugs in real-world, nontrial settings,” Brooks said. “The goal of our study was to investigate outcomes and identify clinical factors associated with outcomes.”
The multicenter, retrospective, observational REALBiTE study tracked 209 patients with relapsed/refractory diffuse LBCL at 19 US centers (epcoritamab, n = 139; glofitamab, n = 70; median age at start of treatment, 67 years [58-76]; 62.2% male; 74.2% diffuse LBCL). The median number of lines of therapy was three (range, 1-12).
“Patients who received epcoritamab tended to be slightly older, were more likely to have a history of indolent non-Hodgkin lymphoma prior to their diagnosis of aggressive B-cell lymphoma and were more likely to have an elevated International Prognostic Index score at the start of bispecific therapy, suggesting that these patients may have been slightly older with higher-risk disease compared to those who received glofitamab,” Brooks said.
In total, 172 patients were response-evaluable. The overall response rate was 50.6% (complete response, 23.8%; partial response, 26.7%; stable disease, 5.8%; progressive disease, 43.6%).
The overall and complete response rates were “somewhat lower that what has been published in the pivotal trials of these medicines,” Brooks said. The low progression-free and overall survival rates “highlight the difficulty in managing this group of patients.”
Cytokine release syndrome (CRS) of any grade occurred in 39.2% of patients: 51% in the epcoritamab group and 28.6% in the glofitamab group. Grade ≥3 CRS occurred in 4.3% of patients, who were all taking epcoritamab.
“For epcoritamab, CRS was almost entirely of low grade, and most CRS events occurred around administration of the first full dose of the drug on day 15,” Brooks said. “Similarly, the CRS events for glofitamab were mostly of low grade, though events were observed to occur throughout the step-up dosing. Tocilizumab was administered in about one fifth of the patients.”
In addition, Brooks said, “we found that, among the 19 individuals with paired biopsy samples before and after bispecific therapy, nearly all — 89% — were found to have lost CD20 expression. We expected some patients to experience loss of this important target, but the rate at which we found this to be the case was surprisingly high.”
Brooks added that “clinicians should be acquainted with CRS, ICANS [immune effector cell-associated neurotoxicity syndrome], and mitigation strategies if they are prescribing these medicines. Appropriate and timely management using tocilizumab, steroids, and other adjunctive measures can effectively manage these complications and hopefully allow for the continued delivery of therapy.”
In an interview, Matthew Lunning, DO, associate professor at the University of Nebraska Medical Center/Fred & Pamela Buffett Cancer Center, Omaha, who didn’t take part in the new study, said the findings aren’t bad news. Instead, they’re “practical news,” because they offer insight into how the drugs work.
“The big lesson from this and other trials is the importance of assessing for CD20 expression prior to taking a bispecific off the shelf, “ he said. “These are learnings that often come after approval.”
He added that it’s clear that, “in more heavily pretreated patients, more disease led to less optimal results and higher risk for toxicities.”
Lunning also noted that both epcoritamab and glofitamab “entered into a crowded and chaotic relapsed/refractory LBCL space based high complete response rates with the opportunity for durability in those complete responses.”
Academic institutions were especially interested, as they can manage CRS and ICANS, but “significantly less enthusiasm has been seen in community practices that expect CRS/ICANS to be in the rear-view mirror if they are going to deliver any bispecific,” he said. “It is not that they don’t have the clinical acumen to manage CRS/ICANS. I believe it is the perception of the lack of supportive infrastructure necessary to manage these toxicities.”
There was no study funding. Brooks has reported no disclosures. Other authors have reported various disclosures including relationships with Novartis, AbbVie, Genentech, Genmab, Biogen, Amgen, and others. Lunning has disclosed ties with AbbVie, Genmab, Kite, Bristol-Myers Squibb, Regeneron, and ADC Therapeutics.
A version of this article first appeared on Medscape.com.
In a presentation at the American Society of Hematology (ASH) 2024 Annual Meeting, researchers reported that of 172 patients treated with the drugs who had evaluable responses over a median follow-up of 5 months, median progression-free survival was 2.7 months (95% CI, 2.0-3.9) and median overall survival was 7.2 months (95% CI, 6.1–not reached).
It’s important to consider the real-world nature of the study’s patient population, said first author Taylor R. Brooks, MD, of Cleveland Clinic, Ohio, in an interview. “Compared to pivotal trials, our cohort was enriched for patients with high-risk features, with almost three quarters having some comorbidity that would’ve excluded them from one of the [earlier] studies.”
He added that “though individuals eligible to receive these medicines may be more sick with high-risk disease, a sizable fraction will respond, and some will maintain remissions.’”
According to Brooks, about one third of patients with diffuse LBCL relapse after standard front-line R-CHOP therapy. “The prognosis is poor for patients who are not candidates for aggressive salvage chemotherapy and for those who relapse after two or more lines,” Brooks said. “T cell–engaging bispecific antibodies have emerged as a promising option for patients with relapsed or refractory large B-cell lymphoma, given their favorable rates and duration of responses as well as their manageable rates of toxicities.”
The Food and Drug Administration (FDA) granted accelerated approval for epcoritamab and glofitamab in 2023.
“With increasing uptake into clinical practice following the FDA approvals, there is increasing interest in assessing the efficacy and safety of these drugs in real-world, nontrial settings,” Brooks said. “The goal of our study was to investigate outcomes and identify clinical factors associated with outcomes.”
The multicenter, retrospective, observational REALBiTE study tracked 209 patients with relapsed/refractory diffuse LBCL at 19 US centers (epcoritamab, n = 139; glofitamab, n = 70; median age at start of treatment, 67 years [58-76]; 62.2% male; 74.2% diffuse LBCL). The median number of lines of therapy was three (range, 1-12).
“Patients who received epcoritamab tended to be slightly older, were more likely to have a history of indolent non-Hodgkin lymphoma prior to their diagnosis of aggressive B-cell lymphoma and were more likely to have an elevated International Prognostic Index score at the start of bispecific therapy, suggesting that these patients may have been slightly older with higher-risk disease compared to those who received glofitamab,” Brooks said.
In total, 172 patients were response-evaluable. The overall response rate was 50.6% (complete response, 23.8%; partial response, 26.7%; stable disease, 5.8%; progressive disease, 43.6%).
The overall and complete response rates were “somewhat lower that what has been published in the pivotal trials of these medicines,” Brooks said. The low progression-free and overall survival rates “highlight the difficulty in managing this group of patients.”
Cytokine release syndrome (CRS) of any grade occurred in 39.2% of patients: 51% in the epcoritamab group and 28.6% in the glofitamab group. Grade ≥3 CRS occurred in 4.3% of patients, who were all taking epcoritamab.
“For epcoritamab, CRS was almost entirely of low grade, and most CRS events occurred around administration of the first full dose of the drug on day 15,” Brooks said. “Similarly, the CRS events for glofitamab were mostly of low grade, though events were observed to occur throughout the step-up dosing. Tocilizumab was administered in about one fifth of the patients.”
In addition, Brooks said, “we found that, among the 19 individuals with paired biopsy samples before and after bispecific therapy, nearly all — 89% — were found to have lost CD20 expression. We expected some patients to experience loss of this important target, but the rate at which we found this to be the case was surprisingly high.”
Brooks added that “clinicians should be acquainted with CRS, ICANS [immune effector cell-associated neurotoxicity syndrome], and mitigation strategies if they are prescribing these medicines. Appropriate and timely management using tocilizumab, steroids, and other adjunctive measures can effectively manage these complications and hopefully allow for the continued delivery of therapy.”
In an interview, Matthew Lunning, DO, associate professor at the University of Nebraska Medical Center/Fred & Pamela Buffett Cancer Center, Omaha, who didn’t take part in the new study, said the findings aren’t bad news. Instead, they’re “practical news,” because they offer insight into how the drugs work.
“The big lesson from this and other trials is the importance of assessing for CD20 expression prior to taking a bispecific off the shelf, “ he said. “These are learnings that often come after approval.”
He added that it’s clear that, “in more heavily pretreated patients, more disease led to less optimal results and higher risk for toxicities.”
Lunning also noted that both epcoritamab and glofitamab “entered into a crowded and chaotic relapsed/refractory LBCL space based high complete response rates with the opportunity for durability in those complete responses.”
Academic institutions were especially interested, as they can manage CRS and ICANS, but “significantly less enthusiasm has been seen in community practices that expect CRS/ICANS to be in the rear-view mirror if they are going to deliver any bispecific,” he said. “It is not that they don’t have the clinical acumen to manage CRS/ICANS. I believe it is the perception of the lack of supportive infrastructure necessary to manage these toxicities.”
There was no study funding. Brooks has reported no disclosures. Other authors have reported various disclosures including relationships with Novartis, AbbVie, Genentech, Genmab, Biogen, Amgen, and others. Lunning has disclosed ties with AbbVie, Genmab, Kite, Bristol-Myers Squibb, Regeneron, and ADC Therapeutics.
A version of this article first appeared on Medscape.com.
FROM ASH 2024
ASH 2024: New Leukemia Txs, Fewer Blood Clots With GLP-1 Rxs
Children’s Disorders: Major Progress in B-Cell Acute Lymphoblastic Leukemia (B-ALL), Immune Thrombocytopenic Purpura (ITP)
While B-ALL is the most common childhood cancer and one of the most treatable, some patients face grim outcomes after they relapse following chemotherapy, said Cynthia E. Dunbar, MD, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute.
A new study reports that adding the targeted cancer drug blinatumomab (Blincyto) to chemotherapy boosted disease-free survival in standard-risk pediatric patients. “They definitively demonstrate a benefit with the addition of this immunotherapeutic drug, achieving 97% disease-free survival at 3 years on the blinatumomab plus chemotherapy arm compared to 90% for the control arm with standard therapies alone,” Dunbar said. “This trial will establish the addition of blinatumomab for childhood B-ALL as standard of care.”
A reporter asked Dunbar about the risk for severe immune activation syndrome. “These immune cell engagers can result in cytokine release syndrome and other severe immune activation consequences,” she said. “However, it appears that children seem to be less susceptible to those, at least in terms of severity, than adults. In this study, the complications that occurred didn’t result in mortality and were easily treatable. So that was not a major drawback to the addition of this drug.”
The blinatumomab study is sponsored by Children’s Oncology Group.
In ITP, thrombopoietin (TPO) agonists such as eltrombopag (Promacta) are a mainstay of second- or third-line treatment in children and adults with severe cases, Dunbar said. “However, TPO agonists are generally only given after months to years of failures of corticosteroids, IVIG [intravenous immunoglobulin], or splenectomy.”
In the phase 3, randomized, controlled PINES trial, researchers explored whether the drug could improve outcomes in children with untreated or very recent-onset severe ITP vs standard of care.
“The children treated with eltrombopag had double the response rate with a much lower need for rescue therapies,” Dunbar said. The percentage of patients who received rescue therapy was 19% in the eltrombopag arm (15/78) vs 46% in the control arm (18/39, P = .002).
“Given the potential short- and long-term consequences of corticosteroids and other standard treatments in children, this study is encouraging and will likely result in a change in the standard of care for pediatric ITP,” Dunbar said.
The eltrombopag study is sponsored by the ITP Consortium of North America and funded by Novartis.
Fewer Blood Clots: Another Big Benefit for Weight Loss Drugs?
Mikkael A. Sekeres, MD, MS, of the Sylvester Comprehensive Cancer Center at the University of Miami in Florida, highlighted an analysis of whether GLP-1 receptor agonists, initially approved as type 2 diabetes treatments, affect the risk for VTE.
Researchers tracked patients with type 2 diabetes — 366,369 who received the drugs and 290,219 who took dipeptidyl peptidase 4 inhibitors. The patients who took GLP-1 agonists “had lower rates of venous thromboembolic events after 1 year,” Sekeres said. “The risk reduction was actually pretty substantial.”
In these patients, the risk for VTE was 18% lower (hazard ratio [HR], 0.82; 95% CI, 0.77-0.88), and there were 22% and 15% reductions in pulmonary embolisms and deep venous thrombosis, respectively (HR, 0.78; 95% CI, 0.71-0.86 and HR, 0.85; 95% CI, 0.79-0.92).
Drug Regimen Improves Outcomes in Chronic Lymphocytic Leukemia (CLL)
An interim analysis of an open-label, randomized, phase 3 trial of patients with untreated CLL “demonstrated superior progression-free survival with acalabrutinib and venetoclax versus what we consider more classic chemotherapy of fludarabine, Cytoxan [cyclophosphamide], and rituximab or bendamustine and rituximab,” Sekeres said. “Similar findings were seen with acalabrutinib, venetoclax, and obinutuzumab vs that classic chemotherapy.”
Overall response rates were 93% for both the acalabrutinib/venetoclax regimens vs 75% for bendamustine/rituximab, Sekeres noted, and overall survival was higher for acalabrutinib/venetoclax vs the two classic chemotherapy regimens (HR, 0.33; P < .0001).
However, Sekeres questioned the value of comparing acalabrutinib/venetoclax with classical chemotherapy regimens. “A lot of times we have a lot of new, really good, really effective therapy to offer to patients that isn’t as toxic as previous chemotherapy.”
In contrast, fludarabine, cyclophosphamide, and rituximab are “your grandmother’s or your grandfather’s chemotherapy. It’s pretty toxic stuff,” he said.
Sekeres said it would have been better to compare acalabrutinib/venetoclax with a Bruton tyrosine kinase inhibitor–based regimen.
The German CLL Study Group is listed as the trial’s sponsor, and AstraZeneca is a collaborator. Dunbar disclosed research funding from Novartis. Sekeres had no relevant disclosures.
A version of this article appeared on Medscape.com.
Children’s Disorders: Major Progress in B-Cell Acute Lymphoblastic Leukemia (B-ALL), Immune Thrombocytopenic Purpura (ITP)
While B-ALL is the most common childhood cancer and one of the most treatable, some patients face grim outcomes after they relapse following chemotherapy, said Cynthia E. Dunbar, MD, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute.
A new study reports that adding the targeted cancer drug blinatumomab (Blincyto) to chemotherapy boosted disease-free survival in standard-risk pediatric patients. “They definitively demonstrate a benefit with the addition of this immunotherapeutic drug, achieving 97% disease-free survival at 3 years on the blinatumomab plus chemotherapy arm compared to 90% for the control arm with standard therapies alone,” Dunbar said. “This trial will establish the addition of blinatumomab for childhood B-ALL as standard of care.”
A reporter asked Dunbar about the risk for severe immune activation syndrome. “These immune cell engagers can result in cytokine release syndrome and other severe immune activation consequences,” she said. “However, it appears that children seem to be less susceptible to those, at least in terms of severity, than adults. In this study, the complications that occurred didn’t result in mortality and were easily treatable. So that was not a major drawback to the addition of this drug.”
The blinatumomab study is sponsored by Children’s Oncology Group.
In ITP, thrombopoietin (TPO) agonists such as eltrombopag (Promacta) are a mainstay of second- or third-line treatment in children and adults with severe cases, Dunbar said. “However, TPO agonists are generally only given after months to years of failures of corticosteroids, IVIG [intravenous immunoglobulin], or splenectomy.”
In the phase 3, randomized, controlled PINES trial, researchers explored whether the drug could improve outcomes in children with untreated or very recent-onset severe ITP vs standard of care.
“The children treated with eltrombopag had double the response rate with a much lower need for rescue therapies,” Dunbar said. The percentage of patients who received rescue therapy was 19% in the eltrombopag arm (15/78) vs 46% in the control arm (18/39, P = .002).
“Given the potential short- and long-term consequences of corticosteroids and other standard treatments in children, this study is encouraging and will likely result in a change in the standard of care for pediatric ITP,” Dunbar said.
The eltrombopag study is sponsored by the ITP Consortium of North America and funded by Novartis.
Fewer Blood Clots: Another Big Benefit for Weight Loss Drugs?
Mikkael A. Sekeres, MD, MS, of the Sylvester Comprehensive Cancer Center at the University of Miami in Florida, highlighted an analysis of whether GLP-1 receptor agonists, initially approved as type 2 diabetes treatments, affect the risk for VTE.
Researchers tracked patients with type 2 diabetes — 366,369 who received the drugs and 290,219 who took dipeptidyl peptidase 4 inhibitors. The patients who took GLP-1 agonists “had lower rates of venous thromboembolic events after 1 year,” Sekeres said. “The risk reduction was actually pretty substantial.”
In these patients, the risk for VTE was 18% lower (hazard ratio [HR], 0.82; 95% CI, 0.77-0.88), and there were 22% and 15% reductions in pulmonary embolisms and deep venous thrombosis, respectively (HR, 0.78; 95% CI, 0.71-0.86 and HR, 0.85; 95% CI, 0.79-0.92).
Drug Regimen Improves Outcomes in Chronic Lymphocytic Leukemia (CLL)
An interim analysis of an open-label, randomized, phase 3 trial of patients with untreated CLL “demonstrated superior progression-free survival with acalabrutinib and venetoclax versus what we consider more classic chemotherapy of fludarabine, Cytoxan [cyclophosphamide], and rituximab or bendamustine and rituximab,” Sekeres said. “Similar findings were seen with acalabrutinib, venetoclax, and obinutuzumab vs that classic chemotherapy.”
Overall response rates were 93% for both the acalabrutinib/venetoclax regimens vs 75% for bendamustine/rituximab, Sekeres noted, and overall survival was higher for acalabrutinib/venetoclax vs the two classic chemotherapy regimens (HR, 0.33; P < .0001).
However, Sekeres questioned the value of comparing acalabrutinib/venetoclax with classical chemotherapy regimens. “A lot of times we have a lot of new, really good, really effective therapy to offer to patients that isn’t as toxic as previous chemotherapy.”
In contrast, fludarabine, cyclophosphamide, and rituximab are “your grandmother’s or your grandfather’s chemotherapy. It’s pretty toxic stuff,” he said.
Sekeres said it would have been better to compare acalabrutinib/venetoclax with a Bruton tyrosine kinase inhibitor–based regimen.
The German CLL Study Group is listed as the trial’s sponsor, and AstraZeneca is a collaborator. Dunbar disclosed research funding from Novartis. Sekeres had no relevant disclosures.
A version of this article appeared on Medscape.com.
Children’s Disorders: Major Progress in B-Cell Acute Lymphoblastic Leukemia (B-ALL), Immune Thrombocytopenic Purpura (ITP)
While B-ALL is the most common childhood cancer and one of the most treatable, some patients face grim outcomes after they relapse following chemotherapy, said Cynthia E. Dunbar, MD, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute.
A new study reports that adding the targeted cancer drug blinatumomab (Blincyto) to chemotherapy boosted disease-free survival in standard-risk pediatric patients. “They definitively demonstrate a benefit with the addition of this immunotherapeutic drug, achieving 97% disease-free survival at 3 years on the blinatumomab plus chemotherapy arm compared to 90% for the control arm with standard therapies alone,” Dunbar said. “This trial will establish the addition of blinatumomab for childhood B-ALL as standard of care.”
A reporter asked Dunbar about the risk for severe immune activation syndrome. “These immune cell engagers can result in cytokine release syndrome and other severe immune activation consequences,” she said. “However, it appears that children seem to be less susceptible to those, at least in terms of severity, than adults. In this study, the complications that occurred didn’t result in mortality and were easily treatable. So that was not a major drawback to the addition of this drug.”
The blinatumomab study is sponsored by Children’s Oncology Group.
In ITP, thrombopoietin (TPO) agonists such as eltrombopag (Promacta) are a mainstay of second- or third-line treatment in children and adults with severe cases, Dunbar said. “However, TPO agonists are generally only given after months to years of failures of corticosteroids, IVIG [intravenous immunoglobulin], or splenectomy.”
In the phase 3, randomized, controlled PINES trial, researchers explored whether the drug could improve outcomes in children with untreated or very recent-onset severe ITP vs standard of care.
“The children treated with eltrombopag had double the response rate with a much lower need for rescue therapies,” Dunbar said. The percentage of patients who received rescue therapy was 19% in the eltrombopag arm (15/78) vs 46% in the control arm (18/39, P = .002).
“Given the potential short- and long-term consequences of corticosteroids and other standard treatments in children, this study is encouraging and will likely result in a change in the standard of care for pediatric ITP,” Dunbar said.
The eltrombopag study is sponsored by the ITP Consortium of North America and funded by Novartis.
Fewer Blood Clots: Another Big Benefit for Weight Loss Drugs?
Mikkael A. Sekeres, MD, MS, of the Sylvester Comprehensive Cancer Center at the University of Miami in Florida, highlighted an analysis of whether GLP-1 receptor agonists, initially approved as type 2 diabetes treatments, affect the risk for VTE.
Researchers tracked patients with type 2 diabetes — 366,369 who received the drugs and 290,219 who took dipeptidyl peptidase 4 inhibitors. The patients who took GLP-1 agonists “had lower rates of venous thromboembolic events after 1 year,” Sekeres said. “The risk reduction was actually pretty substantial.”
In these patients, the risk for VTE was 18% lower (hazard ratio [HR], 0.82; 95% CI, 0.77-0.88), and there were 22% and 15% reductions in pulmonary embolisms and deep venous thrombosis, respectively (HR, 0.78; 95% CI, 0.71-0.86 and HR, 0.85; 95% CI, 0.79-0.92).
Drug Regimen Improves Outcomes in Chronic Lymphocytic Leukemia (CLL)
An interim analysis of an open-label, randomized, phase 3 trial of patients with untreated CLL “demonstrated superior progression-free survival with acalabrutinib and venetoclax versus what we consider more classic chemotherapy of fludarabine, Cytoxan [cyclophosphamide], and rituximab or bendamustine and rituximab,” Sekeres said. “Similar findings were seen with acalabrutinib, venetoclax, and obinutuzumab vs that classic chemotherapy.”
Overall response rates were 93% for both the acalabrutinib/venetoclax regimens vs 75% for bendamustine/rituximab, Sekeres noted, and overall survival was higher for acalabrutinib/venetoclax vs the two classic chemotherapy regimens (HR, 0.33; P < .0001).
However, Sekeres questioned the value of comparing acalabrutinib/venetoclax with classical chemotherapy regimens. “A lot of times we have a lot of new, really good, really effective therapy to offer to patients that isn’t as toxic as previous chemotherapy.”
In contrast, fludarabine, cyclophosphamide, and rituximab are “your grandmother’s or your grandfather’s chemotherapy. It’s pretty toxic stuff,” he said.
Sekeres said it would have been better to compare acalabrutinib/venetoclax with a Bruton tyrosine kinase inhibitor–based regimen.
The German CLL Study Group is listed as the trial’s sponsor, and AstraZeneca is a collaborator. Dunbar disclosed research funding from Novartis. Sekeres had no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM ASH 2024
National Noncompete Ban Unlikely to Survive Under Trump, Experts Say
Even before the presidential election, the Federal Trade Commission’s (FTC) national ban on noncompete clauses faced a tough battle for survival in the courts.
Now, legal specialists forecast a grim prognosis for the ban under Donald Trump’s return to the White House.
But a federal district’s court ruling put the ban on hold, and the Trump administration isn’t expected to support lifting the ban.
“It is likely that the Trump administration will decline to defend the rule and may not even appeal the district court’s ruling, which means that the ban on noncompetes will not go into effect,” Steven Lubet, JD, a professor emeritus at Northwestern University Pritzker School of Law, Chicago, Illinois, said in an interview.
What’s in a Noncompete Clause?
Noncompete clauses in employee contracts typically restrict when and where workers can take future jobs. In medicine, supporters argue that the clauses are fair. Hospitals and practices provide a base of patients to physicians, they say, in return for their agreement not to go work for a competitor.
But those opposed to these clauses argue that the restrictions harm careers and hurt patients by unfairly preventing physicians from moving to new jobs where they’re needed.
At an April meeting, the FTC board voted 3 to 2 to ban noncompete clauses; some nonprofit organizations and senior executives were expected to be exempt. The FTC estimated that the move would save the healthcare system alone as much as $194 billion over 10 years.
“A pandemic killed a million people in this country, and there are doctors who cannot work because of a noncompete,” declared FTC Commissioner Alvaro Bedoya.
Hospitals protested the move. In a statement, the general counsel for the American Hospital Association called it “bad law, bad policy, and a clear sign of an agency run amok” and said the FTC ignored “mountains of contrary legal precedent and evidence about its adverse impacts on the health care markets.”
Although the American Medical Association does not support a total ban, its House of Delegates adopted policies in 2023 to support the prohibition of noncompete contracts for physicians employed by for-profit and nonprofit hospitals, hospital systems, or staffing companies.
Texas Federal Judge Intervenes to Halt Ban
The ban was supposed to take effect on Sept. 4, 2024. But Texas federal judge Ada E. Brown struck down the ban in an Aug. 20 decision. She ruled that the FTC went beyond its authority.
“The district court based its ruling on a very dubious distinction between ‘unfair practices,’ which the FTC may prohibit, and ‘unfair competition,’ which, according to the court, it may not,” said Lubet.
In fact, the ban should stand, he said. “This is a classic case of the government intervening on behalf of consumers/patients by prohibiting an unfair and harmful employment practice,” Lubet said.
Amanda Hill, an attorney in Austin, Texas, who trains physicians about how to negotiate contracts, has a different take. “The Federal Trade Commission came down hard, and honestly, it really overstepped,” she said in an interview. “Congress needs to write laws, not regulatory bodies. I think all the lawyers went: ‘Good try, but you’re not going to get anywhere with that.’ ”
She noted that physicians themselves are divided over the value of noncompete clauses. “I would say 80% of my clients can’t stand noncompetes.” But another 20% own their own practices and hate the idea of losing their physicians to competitors, she said.
Trump Isn’t Seen as Likely to Support Ban
While the Biden administration firmly supported a ban on noncompete clauses, there isn’t a strict Democratic-Republican divide over whether the agreements are a good idea. Some red states have embraced bans, and Hill said this can make sense from a Republican point of view: “We don’t want to run doctors out of town and out of the state because they think they’re going to be bound by big hospitals and corporate interests.”
In fact, former Florida congressman Matt Gaetz, a Republican briefly tapped as President-elect Trump’s nominee for attorney general, supports noncompete clauses. He filed a friend-of-the-court brief with the Texas judge that supported the FTC’s ruling, saying it is a “vindication of economic freedom and free enterprise.”
But Republicans generally “believe that federal agencies are going too far and beyond the power granted to them by Congress,” Atlanta, Georgia, attorney Benjamin Fink, Esq., said in an interview.
And Trump is no fan of the FTC and its chair, Lina Khan, who may step down. Observers don’t expect that the Trump administration or a newly constituted FTC board will support an appeal of the Texas judge’s ruling.
“I don’t think anybody else — another agency or a private party — could step in place of the FTC if the FTC declines to defend the ban,” Atlanta attorney Neal F. Weinrich, Esq., said in an interview. In that case, “I think it ends.”
Attorneys Weinrich and Fink work at the same firm, which handles noncompete agreements for physicians.
Noncompete Ban Advocates Turn to States
Even if Kamala Harris had won the presidency, a national ban on noncompete clauses would have faced an uphill battle at the Supreme Court.
“The Supreme Court majority has been unsympathetic to administrative agencies, interpreting their authority very narrowly,” said Lubet.
So what happens to noncompete clauses now? While bipartisan bills in Congress have tried to ban them, legislation is unlikely to pass now that Republicans will control both the House and Senate, Fink said.
According to a recent article, 12 states prohibit noncompete clauses for physicians: Alabama, California, Colorado, Delaware, Massachusetts, Montana, New Hampshire, New Mexico, North Dakota, Oklahoma, Rhode Island, and South Dakota.
The remaining states allow noncompetes in some form, often excluding them for employees earning below a certain threshold. For example, in Oregon, noncompete agreements may apply to employees earning more than $113,241. Most states have provisions to adjust the threshold annually. The District of Columbia permits 2-year noncompetes for “medical specialists” earning over $250,000 annually.
Indiana employers can no longer enter into noncompete agreements with primary care providers. Other specialties may be subject to the clauses, except when the physician terminates the contract for cause or when an employer terminates the contract without cause.
“I definitely think states are going to continue to restrict the use of noncompetes,” Fink said.
Lubet has no disclosures. Hill, Fink, and Weinrich represent physicians in contract negotiations.
A version of this article appeared on Medscape.com.
Even before the presidential election, the Federal Trade Commission’s (FTC) national ban on noncompete clauses faced a tough battle for survival in the courts.
Now, legal specialists forecast a grim prognosis for the ban under Donald Trump’s return to the White House.
But a federal district’s court ruling put the ban on hold, and the Trump administration isn’t expected to support lifting the ban.
“It is likely that the Trump administration will decline to defend the rule and may not even appeal the district court’s ruling, which means that the ban on noncompetes will not go into effect,” Steven Lubet, JD, a professor emeritus at Northwestern University Pritzker School of Law, Chicago, Illinois, said in an interview.
What’s in a Noncompete Clause?
Noncompete clauses in employee contracts typically restrict when and where workers can take future jobs. In medicine, supporters argue that the clauses are fair. Hospitals and practices provide a base of patients to physicians, they say, in return for their agreement not to go work for a competitor.
But those opposed to these clauses argue that the restrictions harm careers and hurt patients by unfairly preventing physicians from moving to new jobs where they’re needed.
At an April meeting, the FTC board voted 3 to 2 to ban noncompete clauses; some nonprofit organizations and senior executives were expected to be exempt. The FTC estimated that the move would save the healthcare system alone as much as $194 billion over 10 years.
“A pandemic killed a million people in this country, and there are doctors who cannot work because of a noncompete,” declared FTC Commissioner Alvaro Bedoya.
Hospitals protested the move. In a statement, the general counsel for the American Hospital Association called it “bad law, bad policy, and a clear sign of an agency run amok” and said the FTC ignored “mountains of contrary legal precedent and evidence about its adverse impacts on the health care markets.”
Although the American Medical Association does not support a total ban, its House of Delegates adopted policies in 2023 to support the prohibition of noncompete contracts for physicians employed by for-profit and nonprofit hospitals, hospital systems, or staffing companies.
Texas Federal Judge Intervenes to Halt Ban
The ban was supposed to take effect on Sept. 4, 2024. But Texas federal judge Ada E. Brown struck down the ban in an Aug. 20 decision. She ruled that the FTC went beyond its authority.
“The district court based its ruling on a very dubious distinction between ‘unfair practices,’ which the FTC may prohibit, and ‘unfair competition,’ which, according to the court, it may not,” said Lubet.
In fact, the ban should stand, he said. “This is a classic case of the government intervening on behalf of consumers/patients by prohibiting an unfair and harmful employment practice,” Lubet said.
Amanda Hill, an attorney in Austin, Texas, who trains physicians about how to negotiate contracts, has a different take. “The Federal Trade Commission came down hard, and honestly, it really overstepped,” she said in an interview. “Congress needs to write laws, not regulatory bodies. I think all the lawyers went: ‘Good try, but you’re not going to get anywhere with that.’ ”
She noted that physicians themselves are divided over the value of noncompete clauses. “I would say 80% of my clients can’t stand noncompetes.” But another 20% own their own practices and hate the idea of losing their physicians to competitors, she said.
Trump Isn’t Seen as Likely to Support Ban
While the Biden administration firmly supported a ban on noncompete clauses, there isn’t a strict Democratic-Republican divide over whether the agreements are a good idea. Some red states have embraced bans, and Hill said this can make sense from a Republican point of view: “We don’t want to run doctors out of town and out of the state because they think they’re going to be bound by big hospitals and corporate interests.”
In fact, former Florida congressman Matt Gaetz, a Republican briefly tapped as President-elect Trump’s nominee for attorney general, supports noncompete clauses. He filed a friend-of-the-court brief with the Texas judge that supported the FTC’s ruling, saying it is a “vindication of economic freedom and free enterprise.”
But Republicans generally “believe that federal agencies are going too far and beyond the power granted to them by Congress,” Atlanta, Georgia, attorney Benjamin Fink, Esq., said in an interview.
And Trump is no fan of the FTC and its chair, Lina Khan, who may step down. Observers don’t expect that the Trump administration or a newly constituted FTC board will support an appeal of the Texas judge’s ruling.
“I don’t think anybody else — another agency or a private party — could step in place of the FTC if the FTC declines to defend the ban,” Atlanta attorney Neal F. Weinrich, Esq., said in an interview. In that case, “I think it ends.”
Attorneys Weinrich and Fink work at the same firm, which handles noncompete agreements for physicians.
Noncompete Ban Advocates Turn to States
Even if Kamala Harris had won the presidency, a national ban on noncompete clauses would have faced an uphill battle at the Supreme Court.
“The Supreme Court majority has been unsympathetic to administrative agencies, interpreting their authority very narrowly,” said Lubet.
So what happens to noncompete clauses now? While bipartisan bills in Congress have tried to ban them, legislation is unlikely to pass now that Republicans will control both the House and Senate, Fink said.
According to a recent article, 12 states prohibit noncompete clauses for physicians: Alabama, California, Colorado, Delaware, Massachusetts, Montana, New Hampshire, New Mexico, North Dakota, Oklahoma, Rhode Island, and South Dakota.
The remaining states allow noncompetes in some form, often excluding them for employees earning below a certain threshold. For example, in Oregon, noncompete agreements may apply to employees earning more than $113,241. Most states have provisions to adjust the threshold annually. The District of Columbia permits 2-year noncompetes for “medical specialists” earning over $250,000 annually.
Indiana employers can no longer enter into noncompete agreements with primary care providers. Other specialties may be subject to the clauses, except when the physician terminates the contract for cause or when an employer terminates the contract without cause.
“I definitely think states are going to continue to restrict the use of noncompetes,” Fink said.
Lubet has no disclosures. Hill, Fink, and Weinrich represent physicians in contract negotiations.
A version of this article appeared on Medscape.com.
Even before the presidential election, the Federal Trade Commission’s (FTC) national ban on noncompete clauses faced a tough battle for survival in the courts.
Now, legal specialists forecast a grim prognosis for the ban under Donald Trump’s return to the White House.
But a federal district’s court ruling put the ban on hold, and the Trump administration isn’t expected to support lifting the ban.
“It is likely that the Trump administration will decline to defend the rule and may not even appeal the district court’s ruling, which means that the ban on noncompetes will not go into effect,” Steven Lubet, JD, a professor emeritus at Northwestern University Pritzker School of Law, Chicago, Illinois, said in an interview.
What’s in a Noncompete Clause?
Noncompete clauses in employee contracts typically restrict when and where workers can take future jobs. In medicine, supporters argue that the clauses are fair. Hospitals and practices provide a base of patients to physicians, they say, in return for their agreement not to go work for a competitor.
But those opposed to these clauses argue that the restrictions harm careers and hurt patients by unfairly preventing physicians from moving to new jobs where they’re needed.
At an April meeting, the FTC board voted 3 to 2 to ban noncompete clauses; some nonprofit organizations and senior executives were expected to be exempt. The FTC estimated that the move would save the healthcare system alone as much as $194 billion over 10 years.
“A pandemic killed a million people in this country, and there are doctors who cannot work because of a noncompete,” declared FTC Commissioner Alvaro Bedoya.
Hospitals protested the move. In a statement, the general counsel for the American Hospital Association called it “bad law, bad policy, and a clear sign of an agency run amok” and said the FTC ignored “mountains of contrary legal precedent and evidence about its adverse impacts on the health care markets.”
Although the American Medical Association does not support a total ban, its House of Delegates adopted policies in 2023 to support the prohibition of noncompete contracts for physicians employed by for-profit and nonprofit hospitals, hospital systems, or staffing companies.
Texas Federal Judge Intervenes to Halt Ban
The ban was supposed to take effect on Sept. 4, 2024. But Texas federal judge Ada E. Brown struck down the ban in an Aug. 20 decision. She ruled that the FTC went beyond its authority.
“The district court based its ruling on a very dubious distinction between ‘unfair practices,’ which the FTC may prohibit, and ‘unfair competition,’ which, according to the court, it may not,” said Lubet.
In fact, the ban should stand, he said. “This is a classic case of the government intervening on behalf of consumers/patients by prohibiting an unfair and harmful employment practice,” Lubet said.
Amanda Hill, an attorney in Austin, Texas, who trains physicians about how to negotiate contracts, has a different take. “The Federal Trade Commission came down hard, and honestly, it really overstepped,” she said in an interview. “Congress needs to write laws, not regulatory bodies. I think all the lawyers went: ‘Good try, but you’re not going to get anywhere with that.’ ”
She noted that physicians themselves are divided over the value of noncompete clauses. “I would say 80% of my clients can’t stand noncompetes.” But another 20% own their own practices and hate the idea of losing their physicians to competitors, she said.
Trump Isn’t Seen as Likely to Support Ban
While the Biden administration firmly supported a ban on noncompete clauses, there isn’t a strict Democratic-Republican divide over whether the agreements are a good idea. Some red states have embraced bans, and Hill said this can make sense from a Republican point of view: “We don’t want to run doctors out of town and out of the state because they think they’re going to be bound by big hospitals and corporate interests.”
In fact, former Florida congressman Matt Gaetz, a Republican briefly tapped as President-elect Trump’s nominee for attorney general, supports noncompete clauses. He filed a friend-of-the-court brief with the Texas judge that supported the FTC’s ruling, saying it is a “vindication of economic freedom and free enterprise.”
But Republicans generally “believe that federal agencies are going too far and beyond the power granted to them by Congress,” Atlanta, Georgia, attorney Benjamin Fink, Esq., said in an interview.
And Trump is no fan of the FTC and its chair, Lina Khan, who may step down. Observers don’t expect that the Trump administration or a newly constituted FTC board will support an appeal of the Texas judge’s ruling.
“I don’t think anybody else — another agency or a private party — could step in place of the FTC if the FTC declines to defend the ban,” Atlanta attorney Neal F. Weinrich, Esq., said in an interview. In that case, “I think it ends.”
Attorneys Weinrich and Fink work at the same firm, which handles noncompete agreements for physicians.
Noncompete Ban Advocates Turn to States
Even if Kamala Harris had won the presidency, a national ban on noncompete clauses would have faced an uphill battle at the Supreme Court.
“The Supreme Court majority has been unsympathetic to administrative agencies, interpreting their authority very narrowly,” said Lubet.
So what happens to noncompete clauses now? While bipartisan bills in Congress have tried to ban them, legislation is unlikely to pass now that Republicans will control both the House and Senate, Fink said.
According to a recent article, 12 states prohibit noncompete clauses for physicians: Alabama, California, Colorado, Delaware, Massachusetts, Montana, New Hampshire, New Mexico, North Dakota, Oklahoma, Rhode Island, and South Dakota.
The remaining states allow noncompetes in some form, often excluding them for employees earning below a certain threshold. For example, in Oregon, noncompete agreements may apply to employees earning more than $113,241. Most states have provisions to adjust the threshold annually. The District of Columbia permits 2-year noncompetes for “medical specialists” earning over $250,000 annually.
Indiana employers can no longer enter into noncompete agreements with primary care providers. Other specialties may be subject to the clauses, except when the physician terminates the contract for cause or when an employer terminates the contract without cause.
“I definitely think states are going to continue to restrict the use of noncompetes,” Fink said.
Lubet has no disclosures. Hill, Fink, and Weinrich represent physicians in contract negotiations.
A version of this article appeared on Medscape.com.
Blood Buddies: Can Mentorship Revive Classical Hematology?
But when it comes to turning people on to the idea of a career in classical hematology (CH), there may be no more powerful influence than a mentor who loves their job. That’s why the field is focusing so much on supporting mentors and mentees amid a stark shortage of classical hematologists.
“Mentorship is key for maintaining trainee interest in the field and for providing role models for career growth,” said Rakhi P. Naik, MD, MHS, associate professor of medicine and director of the Hematology Fellowship Track at Johns Hopkins University, Baltimore, Maryland, in an interview. “This collaboration is especially critical because there are so few trainees and so few mentors currently in the field.”
Now there’s new research backing up the power of mentorship, even when it’s only provided virtually, and a brand-new program aims to unite more mentors and mentees.
Here’s a closer look at mentor-focused efforts to attract medical students to CH.
How Severe Is the Shortage in CH?
Patients with conditions treated by classical hematologists are waiting months for appointments at many outpatient centers, with some being forced to wait 6 months or more, said Srikanth Nagalla, MD, chief of benign hematology at Miami Cancer Institute, Florida, in an interview.
The shortage is creating dire problems in the inpatient setting too, Nagalla said. “Serious blood disorders like heparin-induced thrombocytopenia, acute chest syndrome [a complication of sickle cell disease], and thrombotic thrombocytopenic purpura have to be diagnosed and treated in a timely manner. If not, the morbidity and mortality are really high.”
If classical hematologists aren’t available, he said, oncologists and others not trained in hematology will need to cover these patients.
Hematologist Ariela Marshall, MD, associate professor of medicine at the University of Minnesota in Minneapolis, noted in an interview that the CH shortage comes at a time when medical advances and an aging population are boosting the number of patients with noncancerous blood disorders. Older people are at greater risk for blood clots, she said. And lifespans for patients with bleeding and clotting disorders are rising thanks to effective new treatments.
“Because of our larger patient population in CH, we are going to need more classical hematologists to follow them for longer and longer periods of time,” she said.
There’s no sign yet that newly minted physicians will take up the slack in CH. A 2019 study found that just 4.6% of 626 of hematology/oncology fellows said they planned to go into CH, also known as benign hematology, vs 67.1% who expected to treat patients with solid tumors, blood cancer, or both. The rest, 24.6%, planned to work in CH plus the two oncology fields.
Why Does a Shortage Exist?
“The reasons are complex, but one of the most important factors was the combining of the adult hematology and medical oncology training programs by the Accreditation Council for Graduate Medical Education in 1995,” Naik said. “After that time, the majority of fellowship training programs went from having separate programs for hematology and medical oncology to combining the training for the two specialties into one. Because most of these combined training programs resided within Cancer Centers, classical hematology training slowly became de-emphasized.”
As a result, fewer fellows ended up specializing in CH, she said.
The field of CH also appears to suffer from a less than enticing reputation. According to a 2019 study coauthored by Marshall, surveys of thousands of hematology/oncology fellows found that “hematology, particularly benign hematology, was viewed as having poorer income potential, research funding, job availability, and job security than oncology.”
Regarding pay, Marshall said the good news is that many classical hematologists work in academia, where it’s common for pay to be “equitable across hematology/oncology divisions and based more on academic rank and other factors rather than subspecialty within hematology oncology.”
However, she noted, “this may differ at institutions where hematology and oncology are different departments. For example, centers where oncology is its own department, and hematology is part of the department of medicine.”
As for job availability, Naik said that there’s plenty of demand. “In academics, it is clear that there are jobs available everywhere, but trainees are often worried about job prospects in private practice. While classical hematology jobs in private practice are not widely advertised, I can attest that there is no shortage of need,” she said. “Many private practices do not specifically advertise for classical hematologists because they assume that classical hematology experts are not available. But I assure you that every private practice my trainees have ever approached is always ecstatic to hire a classical hematologist.”
Why Are Mentors Important?
Mentorship is crucial to promoting the value of CH as a great career choice in a competitive environment, classical hematologists say. “We can motivate trainees by showing how the disease states themselves are so fascinating and how the treatments are showing great outcomes,” Nagalla said. “We can show positive results, how patient lives can be changed, and how well-respected across the system [we] are.”
As a selling point, classical hematologists like to emphasize that their field requires intensive detective work. “Let’s say a patient comes with anemia, which might have 15 different causes. You get some labs, and then you systemically rule in or rule out most of these on the differential diagnosis,” Nagalla said. “Then once you narrow it down, you get more labs. You keep going to the next step and next step, and so finally you come to a conclusion.”
As for therapy, Marshall said that “while for many cancers there are specific treatment recommendations for patients with a specific cancer type at a specific stage, there is not always a specific treatment recommendation (or a ‘right answer’) for our CH patients. Treatment planning depends strongly on a patient’s preferences, other medical conditions, and a discussion about risks [and] benefits of different treatment options such that two patients with the same condition may choose two different treatment options.”
Marshall also emphasizes to trainees that “CH is a broad field. Physicians and trainees are able to interact and collaborate with physicians in other specialties such as gastroenterology, cardiology, ob/gyn, and surgical specialties.”
Does Research Support Mentorship in CH?
The 2019 study that revealed just 4.6% of fellows planned to go into CH found that “fellows who planned to enter hematology-only careers were significantly more likely to report having clinical training and mentorship experiences in hematology throughout their training relative to fellows with oncology-only or combined hematology/oncology career plans.”
Now there are more data to support mentorships. For a study published in Blood Advances in September 2024, Zoya Qureshy, MD, an internal medicine chief resident at the University of California at San Diego, and colleagues evaluated a year-long external membership program implemented by the American Society of Hematology (ASH) Medical Educators Institute.
The program linked 35 US hematology/oncology fellows (80% female, 46% White, 35% Asian) who were interested in CH to 34 North American faculty members. The pairs were told to meet virtually once a month.
Of 30 mentees and 23 mentors surveyed, 94% and 85%, respectively, said their pairings were good matches. Two thirds of the mentees accepted faculty positions in CH after their mentorships.
“Our study showed that external mentorship in a virtual format is feasible,” Qureshy said in an interview. “Additionally, external mentorship provided benefits such as different perspectives and the opportunity for mentorship for those who may not have it in their field of interest at their home institution.”
Qureshy added that “one strength of our mentorship program was that mentoring pairs were meticulously assigned based on shared interests and background. Many participants cited this common ground as a reason why they thought their mentoring pair was a good match.”
There’s an important caveat: Most of the mentees weren’t new to CH. About 70% had previously worked with a mentor in the CH field, and 86% had previously conducted research in the field.
What’s Next for Mentorship in CH?
The ASH Hematology-Focused Fellowship Training Program Consortium aims to mint 50 new academic hematologists by 2030 through programs at 12 institutions. “Mentorship is an exciting aspect of the program since it allows classical hematology trainees to form a network of peers nationally and also provides access to mentors across institutions,” Naik said. “And as the workforce grows, there will be more and more role models for future trainees to look up to.”
Moving forward, she said, “we hope to inspire even more institutions to adopt hematology training tracks throughout the country.”
Meanwhile, ASH’s new Classical Hematology Advancement Mentorship is taking applications for its debut 2025 program through January 9, 2025. Trainees will meet monthly with mentors both virtually and in person. Applicants must have been in their first or second year of hematology/oncology fellowship training at accredited programs in the United States as of July 15, 2024.
Naik, Marshall, Nagalla, and Qureshy have no relevant disclosures.
A version of this article appeared on Medscape.com.
But when it comes to turning people on to the idea of a career in classical hematology (CH), there may be no more powerful influence than a mentor who loves their job. That’s why the field is focusing so much on supporting mentors and mentees amid a stark shortage of classical hematologists.
“Mentorship is key for maintaining trainee interest in the field and for providing role models for career growth,” said Rakhi P. Naik, MD, MHS, associate professor of medicine and director of the Hematology Fellowship Track at Johns Hopkins University, Baltimore, Maryland, in an interview. “This collaboration is especially critical because there are so few trainees and so few mentors currently in the field.”
Now there’s new research backing up the power of mentorship, even when it’s only provided virtually, and a brand-new program aims to unite more mentors and mentees.
Here’s a closer look at mentor-focused efforts to attract medical students to CH.
How Severe Is the Shortage in CH?
Patients with conditions treated by classical hematologists are waiting months for appointments at many outpatient centers, with some being forced to wait 6 months or more, said Srikanth Nagalla, MD, chief of benign hematology at Miami Cancer Institute, Florida, in an interview.
The shortage is creating dire problems in the inpatient setting too, Nagalla said. “Serious blood disorders like heparin-induced thrombocytopenia, acute chest syndrome [a complication of sickle cell disease], and thrombotic thrombocytopenic purpura have to be diagnosed and treated in a timely manner. If not, the morbidity and mortality are really high.”
If classical hematologists aren’t available, he said, oncologists and others not trained in hematology will need to cover these patients.
Hematologist Ariela Marshall, MD, associate professor of medicine at the University of Minnesota in Minneapolis, noted in an interview that the CH shortage comes at a time when medical advances and an aging population are boosting the number of patients with noncancerous blood disorders. Older people are at greater risk for blood clots, she said. And lifespans for patients with bleeding and clotting disorders are rising thanks to effective new treatments.
“Because of our larger patient population in CH, we are going to need more classical hematologists to follow them for longer and longer periods of time,” she said.
There’s no sign yet that newly minted physicians will take up the slack in CH. A 2019 study found that just 4.6% of 626 of hematology/oncology fellows said they planned to go into CH, also known as benign hematology, vs 67.1% who expected to treat patients with solid tumors, blood cancer, or both. The rest, 24.6%, planned to work in CH plus the two oncology fields.
Why Does a Shortage Exist?
“The reasons are complex, but one of the most important factors was the combining of the adult hematology and medical oncology training programs by the Accreditation Council for Graduate Medical Education in 1995,” Naik said. “After that time, the majority of fellowship training programs went from having separate programs for hematology and medical oncology to combining the training for the two specialties into one. Because most of these combined training programs resided within Cancer Centers, classical hematology training slowly became de-emphasized.”
As a result, fewer fellows ended up specializing in CH, she said.
The field of CH also appears to suffer from a less than enticing reputation. According to a 2019 study coauthored by Marshall, surveys of thousands of hematology/oncology fellows found that “hematology, particularly benign hematology, was viewed as having poorer income potential, research funding, job availability, and job security than oncology.”
Regarding pay, Marshall said the good news is that many classical hematologists work in academia, where it’s common for pay to be “equitable across hematology/oncology divisions and based more on academic rank and other factors rather than subspecialty within hematology oncology.”
However, she noted, “this may differ at institutions where hematology and oncology are different departments. For example, centers where oncology is its own department, and hematology is part of the department of medicine.”
As for job availability, Naik said that there’s plenty of demand. “In academics, it is clear that there are jobs available everywhere, but trainees are often worried about job prospects in private practice. While classical hematology jobs in private practice are not widely advertised, I can attest that there is no shortage of need,” she said. “Many private practices do not specifically advertise for classical hematologists because they assume that classical hematology experts are not available. But I assure you that every private practice my trainees have ever approached is always ecstatic to hire a classical hematologist.”
Why Are Mentors Important?
Mentorship is crucial to promoting the value of CH as a great career choice in a competitive environment, classical hematologists say. “We can motivate trainees by showing how the disease states themselves are so fascinating and how the treatments are showing great outcomes,” Nagalla said. “We can show positive results, how patient lives can be changed, and how well-respected across the system [we] are.”
As a selling point, classical hematologists like to emphasize that their field requires intensive detective work. “Let’s say a patient comes with anemia, which might have 15 different causes. You get some labs, and then you systemically rule in or rule out most of these on the differential diagnosis,” Nagalla said. “Then once you narrow it down, you get more labs. You keep going to the next step and next step, and so finally you come to a conclusion.”
As for therapy, Marshall said that “while for many cancers there are specific treatment recommendations for patients with a specific cancer type at a specific stage, there is not always a specific treatment recommendation (or a ‘right answer’) for our CH patients. Treatment planning depends strongly on a patient’s preferences, other medical conditions, and a discussion about risks [and] benefits of different treatment options such that two patients with the same condition may choose two different treatment options.”
Marshall also emphasizes to trainees that “CH is a broad field. Physicians and trainees are able to interact and collaborate with physicians in other specialties such as gastroenterology, cardiology, ob/gyn, and surgical specialties.”
Does Research Support Mentorship in CH?
The 2019 study that revealed just 4.6% of fellows planned to go into CH found that “fellows who planned to enter hematology-only careers were significantly more likely to report having clinical training and mentorship experiences in hematology throughout their training relative to fellows with oncology-only or combined hematology/oncology career plans.”
Now there are more data to support mentorships. For a study published in Blood Advances in September 2024, Zoya Qureshy, MD, an internal medicine chief resident at the University of California at San Diego, and colleagues evaluated a year-long external membership program implemented by the American Society of Hematology (ASH) Medical Educators Institute.
The program linked 35 US hematology/oncology fellows (80% female, 46% White, 35% Asian) who were interested in CH to 34 North American faculty members. The pairs were told to meet virtually once a month.
Of 30 mentees and 23 mentors surveyed, 94% and 85%, respectively, said their pairings were good matches. Two thirds of the mentees accepted faculty positions in CH after their mentorships.
“Our study showed that external mentorship in a virtual format is feasible,” Qureshy said in an interview. “Additionally, external mentorship provided benefits such as different perspectives and the opportunity for mentorship for those who may not have it in their field of interest at their home institution.”
Qureshy added that “one strength of our mentorship program was that mentoring pairs were meticulously assigned based on shared interests and background. Many participants cited this common ground as a reason why they thought their mentoring pair was a good match.”
There’s an important caveat: Most of the mentees weren’t new to CH. About 70% had previously worked with a mentor in the CH field, and 86% had previously conducted research in the field.
What’s Next for Mentorship in CH?
The ASH Hematology-Focused Fellowship Training Program Consortium aims to mint 50 new academic hematologists by 2030 through programs at 12 institutions. “Mentorship is an exciting aspect of the program since it allows classical hematology trainees to form a network of peers nationally and also provides access to mentors across institutions,” Naik said. “And as the workforce grows, there will be more and more role models for future trainees to look up to.”
Moving forward, she said, “we hope to inspire even more institutions to adopt hematology training tracks throughout the country.”
Meanwhile, ASH’s new Classical Hematology Advancement Mentorship is taking applications for its debut 2025 program through January 9, 2025. Trainees will meet monthly with mentors both virtually and in person. Applicants must have been in their first or second year of hematology/oncology fellowship training at accredited programs in the United States as of July 15, 2024.
Naik, Marshall, Nagalla, and Qureshy have no relevant disclosures.
A version of this article appeared on Medscape.com.
But when it comes to turning people on to the idea of a career in classical hematology (CH), there may be no more powerful influence than a mentor who loves their job. That’s why the field is focusing so much on supporting mentors and mentees amid a stark shortage of classical hematologists.
“Mentorship is key for maintaining trainee interest in the field and for providing role models for career growth,” said Rakhi P. Naik, MD, MHS, associate professor of medicine and director of the Hematology Fellowship Track at Johns Hopkins University, Baltimore, Maryland, in an interview. “This collaboration is especially critical because there are so few trainees and so few mentors currently in the field.”
Now there’s new research backing up the power of mentorship, even when it’s only provided virtually, and a brand-new program aims to unite more mentors and mentees.
Here’s a closer look at mentor-focused efforts to attract medical students to CH.
How Severe Is the Shortage in CH?
Patients with conditions treated by classical hematologists are waiting months for appointments at many outpatient centers, with some being forced to wait 6 months or more, said Srikanth Nagalla, MD, chief of benign hematology at Miami Cancer Institute, Florida, in an interview.
The shortage is creating dire problems in the inpatient setting too, Nagalla said. “Serious blood disorders like heparin-induced thrombocytopenia, acute chest syndrome [a complication of sickle cell disease], and thrombotic thrombocytopenic purpura have to be diagnosed and treated in a timely manner. If not, the morbidity and mortality are really high.”
If classical hematologists aren’t available, he said, oncologists and others not trained in hematology will need to cover these patients.
Hematologist Ariela Marshall, MD, associate professor of medicine at the University of Minnesota in Minneapolis, noted in an interview that the CH shortage comes at a time when medical advances and an aging population are boosting the number of patients with noncancerous blood disorders. Older people are at greater risk for blood clots, she said. And lifespans for patients with bleeding and clotting disorders are rising thanks to effective new treatments.
“Because of our larger patient population in CH, we are going to need more classical hematologists to follow them for longer and longer periods of time,” she said.
There’s no sign yet that newly minted physicians will take up the slack in CH. A 2019 study found that just 4.6% of 626 of hematology/oncology fellows said they planned to go into CH, also known as benign hematology, vs 67.1% who expected to treat patients with solid tumors, blood cancer, or both. The rest, 24.6%, planned to work in CH plus the two oncology fields.
Why Does a Shortage Exist?
“The reasons are complex, but one of the most important factors was the combining of the adult hematology and medical oncology training programs by the Accreditation Council for Graduate Medical Education in 1995,” Naik said. “After that time, the majority of fellowship training programs went from having separate programs for hematology and medical oncology to combining the training for the two specialties into one. Because most of these combined training programs resided within Cancer Centers, classical hematology training slowly became de-emphasized.”
As a result, fewer fellows ended up specializing in CH, she said.
The field of CH also appears to suffer from a less than enticing reputation. According to a 2019 study coauthored by Marshall, surveys of thousands of hematology/oncology fellows found that “hematology, particularly benign hematology, was viewed as having poorer income potential, research funding, job availability, and job security than oncology.”
Regarding pay, Marshall said the good news is that many classical hematologists work in academia, where it’s common for pay to be “equitable across hematology/oncology divisions and based more on academic rank and other factors rather than subspecialty within hematology oncology.”
However, she noted, “this may differ at institutions where hematology and oncology are different departments. For example, centers where oncology is its own department, and hematology is part of the department of medicine.”
As for job availability, Naik said that there’s plenty of demand. “In academics, it is clear that there are jobs available everywhere, but trainees are often worried about job prospects in private practice. While classical hematology jobs in private practice are not widely advertised, I can attest that there is no shortage of need,” she said. “Many private practices do not specifically advertise for classical hematologists because they assume that classical hematology experts are not available. But I assure you that every private practice my trainees have ever approached is always ecstatic to hire a classical hematologist.”
Why Are Mentors Important?
Mentorship is crucial to promoting the value of CH as a great career choice in a competitive environment, classical hematologists say. “We can motivate trainees by showing how the disease states themselves are so fascinating and how the treatments are showing great outcomes,” Nagalla said. “We can show positive results, how patient lives can be changed, and how well-respected across the system [we] are.”
As a selling point, classical hematologists like to emphasize that their field requires intensive detective work. “Let’s say a patient comes with anemia, which might have 15 different causes. You get some labs, and then you systemically rule in or rule out most of these on the differential diagnosis,” Nagalla said. “Then once you narrow it down, you get more labs. You keep going to the next step and next step, and so finally you come to a conclusion.”
As for therapy, Marshall said that “while for many cancers there are specific treatment recommendations for patients with a specific cancer type at a specific stage, there is not always a specific treatment recommendation (or a ‘right answer’) for our CH patients. Treatment planning depends strongly on a patient’s preferences, other medical conditions, and a discussion about risks [and] benefits of different treatment options such that two patients with the same condition may choose two different treatment options.”
Marshall also emphasizes to trainees that “CH is a broad field. Physicians and trainees are able to interact and collaborate with physicians in other specialties such as gastroenterology, cardiology, ob/gyn, and surgical specialties.”
Does Research Support Mentorship in CH?
The 2019 study that revealed just 4.6% of fellows planned to go into CH found that “fellows who planned to enter hematology-only careers were significantly more likely to report having clinical training and mentorship experiences in hematology throughout their training relative to fellows with oncology-only or combined hematology/oncology career plans.”
Now there are more data to support mentorships. For a study published in Blood Advances in September 2024, Zoya Qureshy, MD, an internal medicine chief resident at the University of California at San Diego, and colleagues evaluated a year-long external membership program implemented by the American Society of Hematology (ASH) Medical Educators Institute.
The program linked 35 US hematology/oncology fellows (80% female, 46% White, 35% Asian) who were interested in CH to 34 North American faculty members. The pairs were told to meet virtually once a month.
Of 30 mentees and 23 mentors surveyed, 94% and 85%, respectively, said their pairings were good matches. Two thirds of the mentees accepted faculty positions in CH after their mentorships.
“Our study showed that external mentorship in a virtual format is feasible,” Qureshy said in an interview. “Additionally, external mentorship provided benefits such as different perspectives and the opportunity for mentorship for those who may not have it in their field of interest at their home institution.”
Qureshy added that “one strength of our mentorship program was that mentoring pairs were meticulously assigned based on shared interests and background. Many participants cited this common ground as a reason why they thought their mentoring pair was a good match.”
There’s an important caveat: Most of the mentees weren’t new to CH. About 70% had previously worked with a mentor in the CH field, and 86% had previously conducted research in the field.
What’s Next for Mentorship in CH?
The ASH Hematology-Focused Fellowship Training Program Consortium aims to mint 50 new academic hematologists by 2030 through programs at 12 institutions. “Mentorship is an exciting aspect of the program since it allows classical hematology trainees to form a network of peers nationally and also provides access to mentors across institutions,” Naik said. “And as the workforce grows, there will be more and more role models for future trainees to look up to.”
Moving forward, she said, “we hope to inspire even more institutions to adopt hematology training tracks throughout the country.”
Meanwhile, ASH’s new Classical Hematology Advancement Mentorship is taking applications for its debut 2025 program through January 9, 2025. Trainees will meet monthly with mentors both virtually and in person. Applicants must have been in their first or second year of hematology/oncology fellowship training at accredited programs in the United States as of July 15, 2024.
Naik, Marshall, Nagalla, and Qureshy have no relevant disclosures.
A version of this article appeared on Medscape.com.
Pharmacist Advocates for Early Adoption of Quadruple Therapy in HFrEF Treatment
SAN DIEGO — An Air Force pharmacist urged colleagues in the military to advocate for the gold standard of quadruple therapy in patients with heart failure with reduced ejection fraction (HFrEF). “When possible, initiate and optimize quadruple therapy before discharge; don’t leave it for a primary care manager (PCM) to handle,” said Maj. Elizabeth Tesch, PharmD, of Maxwell Air Force Base, Montgomery, Ala., in a presentation here at the Joint Federal Pharmacy Seminar. Tesch also cautioned colleagues about the proper use of IV inotropes and vasodilators in congestive heart failure and warned of the dangers of polypharmacy.
“It’s just as important to use medications that provide a mortality benefit in these patients as it is to remove things that are either harmful or lack trial benefit data,” Tesch said.
In patients with acute heart failure and systolic blood pressure < 90 mmHg, guidelines recommend using both an inotrope and a vasopressor. “There tends to be better data about 2 of them together vs just cranking up a vasoconstrictor, which we tend to sometimes to do when a patient’s blood pressure is bottoming out,” Tesch explained. “But in these patients specifically, that tends to lead to increased afterload, difficulty with cardiac output, and then increased risk of ischemia. So it tends to be better to use both.”
Ideally, Tesch said, patients stabilize within a couple days. In cases of HFrEF, this is when quadruple therapy can enter the picture.
Quadruple therapy consists of the “4 pillars”: a sodium-glucose co-transporter 2 inhibitor (SGLT2i), a β blocker, a mineralocorticoid receptor antagonist (MRA), and either an angiotensin receptor neprilysin inhibitor (ARNI), an angiotensin‐converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB).
Tesch noted that the need for titration varies by drug. β blockers typically will need the most up-titration, often in several steps, followed by ARNIs. MRAs may require only one titration or even not at all, and SGLT2 inhibitors do not require titration.
“[Clinicians] are most comfortable giving ACE inhibitors, ARBs, and β blockers to patients, she said. But new research suggests there is a 10.3% jump in mortality risk (absolute risk difference) compared to ACEi/ β blocker/ARB therapy. Additionally, a 2022 systematic review linked quadruple therapy to a gain of 5 years of life (ranging from 2.5 to7.5 years) for 70-year-old patients compared to no therapy.
“I don't know how many times I've had a conversation along the lines of, ‘Hey, can we go ahead and start an SGLT2 on this patient?’ only to hear, ‘We'll give that to the PCM [primary care manager]. That sounds like a PCM thing. You just want to get them out of here, it’s a PCM problem.’”
But quick initiation of treatment is crucial. “We're seeing very real mortality benefit data very quickly in these patients,” Tesch said.
As for polypharmacy, Tesch highlighted the importance of reducing mediation load when possible. “If they have nothing else wrong, these patients will walk out the door on quadruple therapy and perhaps a diuretic, but they probably have a lot more going on,” she said. “All of us in this room are fully aware of what polypharmacy can do to these patients: increased drug interactions, side effects, higher cost, and decreased patient compliance. This is a problem for the heart failure population that really translates into readmissions and increased mortality. We've got to be able to peel off things that are either harmful or not helping.”
Statins, for example, have questionable benefit in HFrEF without coronary artery disease or hyperlipidemia, she said. Oral iron and vitamin D supplementation also have uncertain benefits in the HFrEF population.
Tesch highlighted a pair of reports – one from 2024 and the other from 2022 – that recommended certain therapies in heart failure, including the antidepressant citalopram (Celexa), the hypertension/urinary retention drug doxazosin (Cardura), and DPP-4 inhibitors (eg, diabetes/weight-loss drugs such as liraglutide [Saxenda]).
Tesch has no disclosures.
SAN DIEGO — An Air Force pharmacist urged colleagues in the military to advocate for the gold standard of quadruple therapy in patients with heart failure with reduced ejection fraction (HFrEF). “When possible, initiate and optimize quadruple therapy before discharge; don’t leave it for a primary care manager (PCM) to handle,” said Maj. Elizabeth Tesch, PharmD, of Maxwell Air Force Base, Montgomery, Ala., in a presentation here at the Joint Federal Pharmacy Seminar. Tesch also cautioned colleagues about the proper use of IV inotropes and vasodilators in congestive heart failure and warned of the dangers of polypharmacy.
“It’s just as important to use medications that provide a mortality benefit in these patients as it is to remove things that are either harmful or lack trial benefit data,” Tesch said.
In patients with acute heart failure and systolic blood pressure < 90 mmHg, guidelines recommend using both an inotrope and a vasopressor. “There tends to be better data about 2 of them together vs just cranking up a vasoconstrictor, which we tend to sometimes to do when a patient’s blood pressure is bottoming out,” Tesch explained. “But in these patients specifically, that tends to lead to increased afterload, difficulty with cardiac output, and then increased risk of ischemia. So it tends to be better to use both.”
Ideally, Tesch said, patients stabilize within a couple days. In cases of HFrEF, this is when quadruple therapy can enter the picture.
Quadruple therapy consists of the “4 pillars”: a sodium-glucose co-transporter 2 inhibitor (SGLT2i), a β blocker, a mineralocorticoid receptor antagonist (MRA), and either an angiotensin receptor neprilysin inhibitor (ARNI), an angiotensin‐converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB).
Tesch noted that the need for titration varies by drug. β blockers typically will need the most up-titration, often in several steps, followed by ARNIs. MRAs may require only one titration or even not at all, and SGLT2 inhibitors do not require titration.
“[Clinicians] are most comfortable giving ACE inhibitors, ARBs, and β blockers to patients, she said. But new research suggests there is a 10.3% jump in mortality risk (absolute risk difference) compared to ACEi/ β blocker/ARB therapy. Additionally, a 2022 systematic review linked quadruple therapy to a gain of 5 years of life (ranging from 2.5 to7.5 years) for 70-year-old patients compared to no therapy.
“I don't know how many times I've had a conversation along the lines of, ‘Hey, can we go ahead and start an SGLT2 on this patient?’ only to hear, ‘We'll give that to the PCM [primary care manager]. That sounds like a PCM thing. You just want to get them out of here, it’s a PCM problem.’”
But quick initiation of treatment is crucial. “We're seeing very real mortality benefit data very quickly in these patients,” Tesch said.
As for polypharmacy, Tesch highlighted the importance of reducing mediation load when possible. “If they have nothing else wrong, these patients will walk out the door on quadruple therapy and perhaps a diuretic, but they probably have a lot more going on,” she said. “All of us in this room are fully aware of what polypharmacy can do to these patients: increased drug interactions, side effects, higher cost, and decreased patient compliance. This is a problem for the heart failure population that really translates into readmissions and increased mortality. We've got to be able to peel off things that are either harmful or not helping.”
Statins, for example, have questionable benefit in HFrEF without coronary artery disease or hyperlipidemia, she said. Oral iron and vitamin D supplementation also have uncertain benefits in the HFrEF population.
Tesch highlighted a pair of reports – one from 2024 and the other from 2022 – that recommended certain therapies in heart failure, including the antidepressant citalopram (Celexa), the hypertension/urinary retention drug doxazosin (Cardura), and DPP-4 inhibitors (eg, diabetes/weight-loss drugs such as liraglutide [Saxenda]).
Tesch has no disclosures.
SAN DIEGO — An Air Force pharmacist urged colleagues in the military to advocate for the gold standard of quadruple therapy in patients with heart failure with reduced ejection fraction (HFrEF). “When possible, initiate and optimize quadruple therapy before discharge; don’t leave it for a primary care manager (PCM) to handle,” said Maj. Elizabeth Tesch, PharmD, of Maxwell Air Force Base, Montgomery, Ala., in a presentation here at the Joint Federal Pharmacy Seminar. Tesch also cautioned colleagues about the proper use of IV inotropes and vasodilators in congestive heart failure and warned of the dangers of polypharmacy.
“It’s just as important to use medications that provide a mortality benefit in these patients as it is to remove things that are either harmful or lack trial benefit data,” Tesch said.
In patients with acute heart failure and systolic blood pressure < 90 mmHg, guidelines recommend using both an inotrope and a vasopressor. “There tends to be better data about 2 of them together vs just cranking up a vasoconstrictor, which we tend to sometimes to do when a patient’s blood pressure is bottoming out,” Tesch explained. “But in these patients specifically, that tends to lead to increased afterload, difficulty with cardiac output, and then increased risk of ischemia. So it tends to be better to use both.”
Ideally, Tesch said, patients stabilize within a couple days. In cases of HFrEF, this is when quadruple therapy can enter the picture.
Quadruple therapy consists of the “4 pillars”: a sodium-glucose co-transporter 2 inhibitor (SGLT2i), a β blocker, a mineralocorticoid receptor antagonist (MRA), and either an angiotensin receptor neprilysin inhibitor (ARNI), an angiotensin‐converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB).
Tesch noted that the need for titration varies by drug. β blockers typically will need the most up-titration, often in several steps, followed by ARNIs. MRAs may require only one titration or even not at all, and SGLT2 inhibitors do not require titration.
“[Clinicians] are most comfortable giving ACE inhibitors, ARBs, and β blockers to patients, she said. But new research suggests there is a 10.3% jump in mortality risk (absolute risk difference) compared to ACEi/ β blocker/ARB therapy. Additionally, a 2022 systematic review linked quadruple therapy to a gain of 5 years of life (ranging from 2.5 to7.5 years) for 70-year-old patients compared to no therapy.
“I don't know how many times I've had a conversation along the lines of, ‘Hey, can we go ahead and start an SGLT2 on this patient?’ only to hear, ‘We'll give that to the PCM [primary care manager]. That sounds like a PCM thing. You just want to get them out of here, it’s a PCM problem.’”
But quick initiation of treatment is crucial. “We're seeing very real mortality benefit data very quickly in these patients,” Tesch said.
As for polypharmacy, Tesch highlighted the importance of reducing mediation load when possible. “If they have nothing else wrong, these patients will walk out the door on quadruple therapy and perhaps a diuretic, but they probably have a lot more going on,” she said. “All of us in this room are fully aware of what polypharmacy can do to these patients: increased drug interactions, side effects, higher cost, and decreased patient compliance. This is a problem for the heart failure population that really translates into readmissions and increased mortality. We've got to be able to peel off things that are either harmful or not helping.”
Statins, for example, have questionable benefit in HFrEF without coronary artery disease or hyperlipidemia, she said. Oral iron and vitamin D supplementation also have uncertain benefits in the HFrEF population.
Tesch highlighted a pair of reports – one from 2024 and the other from 2022 – that recommended certain therapies in heart failure, including the antidepressant citalopram (Celexa), the hypertension/urinary retention drug doxazosin (Cardura), and DPP-4 inhibitors (eg, diabetes/weight-loss drugs such as liraglutide [Saxenda]).
Tesch has no disclosures.
From Mexico City to the Heights of Leukemia Medicine
His work has helped transform CML into an often-survivable disease instead of one that took the lives of most patients within 5 years.
“It’s been remarkable to see the evolution in CML and to be part of that transition as a fellow, as faculty, and as leader of some of the trials,” said Cortes, who directs the Georgia Cancer Center at Augusta University. “I’m the luckiest person in the world.”
In an interview, Cortes talked about his youth in Mexico, his research path, and his close connections to cancer medicine in Latin America.
Q: You grew up in Mexico City. What was your family like?
A: “My father grew up very poor in a small town in Michoacán in the southwest part of Mexico. In Mexico City, he had a tiny grocery store in an old-fashioned market, and we were lower middle class.
One of the things I learned was to work hard. There’s nobody I know who worked as hard as my father. He opened his store every day of the year, [Mexican] Independence Day or New Year’s or Christmas. He worked hard so we could have a better life than he did.
We learned English from a very young age. My elementary school was called Westminster School because he wanted a school where we would learn English.
As for my mother, she stayed with us [at home] and made sure we did our homework and were taken care of. I learned about being honest and dedicating to what you were doing.”
Q: You trained at the Salvador Zubirán National Institute of Health Sciences and Nutrition in Mexico City. Then what happened?
A: “Through encouragement by my dermatologist older brother and a mentor at the institution where I was training as a hematologist, I decided to come to the United States.
My initial focus was going to be on coagulation and thrombosis. I came to Houston (Texas) for a fellowship at the University of Texas Health Science Center.
Then I started doing my rotation for the malignant part of the fellowship at MD Anderson Cancer Center [Houston]. One of my first rotations was with Susan M. O’Brien, [MD,] who became my greatest mentor throughout my career. I really enjoyed my rotation. I thought she was great clinically, and she was doing research and teaching. That’s what I wanted for my career.”
Q: What drew you to leukemia specifically?
A: “Dr O’Brien worked in leukemia during my initial rotation, and I really loved it. It was hard work, but it was very inspiring to see the clinical research and the things you could for patients. She had a lot of joy doing that.
I told my program director I’d change and transfer to MD Anderson, and I ended up staying at MD Anderson for 23 years.”
Q: What was leukemia research like in those days?
A: “We didn’t have the understanding of the biology and the new drugs that we have now. When I started in Mexico, we didn’t even have hydroxyurea. What we were doing was much more basic. But still, the field sounded like a great field to be involved with because they were doing so many trials and had an outstanding database.
Because of the influence of Dr [Moshe] Talpaz, [MD,] I started getting very involved with CML. In my initial years as a young faculty, I started working with him on interferon. Then imatinib appeared. I saw even from the phase 1 study how impressive the outcomes were in patients who had no response to anything and were in bad shape.”
Q: What CML medications have you worked on?
A: “I’ve been involved with all of them. Imatinib early on, then I led trials with dasatinib and nilotinib. Then, I led the registration trials of bosutinib and ponatinib. More recently, I was part of the development of asciminib.”
Q: What were some of the biggest challenges in CML research?
A: “We had an opportunity to do a lot of analysis about TKIs [tyrosine kinase inhibitors] when these were new drugs. It was a very steep curve of learning, how to monitor and manage side effects.
Then patients were starting to have resistance to two to three TKIs. Ponatinib came along, and it was an incredibly effective drug. But after it was approved, we started to recognize the occurrence of heart attacks and strokes.
That was unexpected and not something that was known for any TKI. It was a big challenge. The drug was taken off the market for some time, and trials were put on hold by the FDA [US Food and Drug Administration].
We scrambled to understand the mechanism of action. For a year or two, it was a stressful time. But eventually we moved past it, and we learned a lot.”
Q: What sort of work have you done in Latin America?
A: “I’ve always been very close to Latin America. I have many good friends and colleagues there, and I’ve always been interested in working with them.
We’ve done research and studies and created an organization called Latin American Leukemia Net to develop more trials in Latin America. The most rewarding thing has been the educational programs for patients that we’ve done, helping them understand the disease, the treatments, and the goals of treatment.
We’ve conducted a number of programs, and they have been effective, well-attended, and well received. I still work with my colleagues to develop local guidelines and do collaborative research.”
Q: What convinced you to leave MD Anderson for Georgia?
A: “I never thought I’d leave MD Anderson. I had my well-oiled machine of clinical trials, my clinic, and my fellowship program. But the one thing that I wanted to see if I could try next was to develop an institution.
That was the goal here, to take the Georgia Cancer Center to NCI [National Cancer Institute] designation. So, I thought, ‘That’s a nice challenge.’ It may be a good opportunity to try a different aspect of what it means to be an oncologist.
There are days that you think, ‘What am I doing here?’ when you have to deal with budgets and personnel and all these things. But it’s part of the process. It’s still good to know that we have a goal, and that we’re going to make it.
Also, I still see my patients, and I enjoy that I still do some research and mentoring.”
Q: What’s the current state of CML treatment?
A: “Many patients have a pretty much normal life expectancy while [on therapy]. Still, one of the goals of many patients is to stop therapy. But that’s a reality only for a small percentage of patients. How can we make that happen for more patients?”
Q: By stopping therapy, do you mean curing the cancer?
A: “Yes, pretty much. You have a good response, you stop the therapy, and it doesn’t come back.
There are also patients who really don’t do well. We hear about CML being with a disease with such a good outcome, but we have patients for whom nothing works. Is it a matter of [needing] another TKI, or do we need to look at something else?”
Q: What do you see on the horizon?
A: “We are developing new approaches like combination therapies. We’re scratching the surface on that. We need to understand which combinations work, and where and when.
And we can make more efficient uses of the drugs we have now in terms of which ones to use when, the doses, the safety profiles. I think we can do better.”
Cortes disclosed consulting for Amphivena, Astellas, Bio-Path, BioLineRx, Bristol Myers Squibb, Daiichi Sankyo, Jazz, Novartis, Pfizer, and Takeda and research funding from Astellas Pharma, Bristol Myers Squibb, Daiichi Sankyo, Immunogen, Jazz, Merus, Novartis, Pfizer, Sun Pharma, Takeda, Tolero and Trovagene.
A version of this article appeared on Medscape.com.
His work has helped transform CML into an often-survivable disease instead of one that took the lives of most patients within 5 years.
“It’s been remarkable to see the evolution in CML and to be part of that transition as a fellow, as faculty, and as leader of some of the trials,” said Cortes, who directs the Georgia Cancer Center at Augusta University. “I’m the luckiest person in the world.”
In an interview, Cortes talked about his youth in Mexico, his research path, and his close connections to cancer medicine in Latin America.
Q: You grew up in Mexico City. What was your family like?
A: “My father grew up very poor in a small town in Michoacán in the southwest part of Mexico. In Mexico City, he had a tiny grocery store in an old-fashioned market, and we were lower middle class.
One of the things I learned was to work hard. There’s nobody I know who worked as hard as my father. He opened his store every day of the year, [Mexican] Independence Day or New Year’s or Christmas. He worked hard so we could have a better life than he did.
We learned English from a very young age. My elementary school was called Westminster School because he wanted a school where we would learn English.
As for my mother, she stayed with us [at home] and made sure we did our homework and were taken care of. I learned about being honest and dedicating to what you were doing.”
Q: You trained at the Salvador Zubirán National Institute of Health Sciences and Nutrition in Mexico City. Then what happened?
A: “Through encouragement by my dermatologist older brother and a mentor at the institution where I was training as a hematologist, I decided to come to the United States.
My initial focus was going to be on coagulation and thrombosis. I came to Houston (Texas) for a fellowship at the University of Texas Health Science Center.
Then I started doing my rotation for the malignant part of the fellowship at MD Anderson Cancer Center [Houston]. One of my first rotations was with Susan M. O’Brien, [MD,] who became my greatest mentor throughout my career. I really enjoyed my rotation. I thought she was great clinically, and she was doing research and teaching. That’s what I wanted for my career.”
Q: What drew you to leukemia specifically?
A: “Dr O’Brien worked in leukemia during my initial rotation, and I really loved it. It was hard work, but it was very inspiring to see the clinical research and the things you could for patients. She had a lot of joy doing that.
I told my program director I’d change and transfer to MD Anderson, and I ended up staying at MD Anderson for 23 years.”
Q: What was leukemia research like in those days?
A: “We didn’t have the understanding of the biology and the new drugs that we have now. When I started in Mexico, we didn’t even have hydroxyurea. What we were doing was much more basic. But still, the field sounded like a great field to be involved with because they were doing so many trials and had an outstanding database.
Because of the influence of Dr [Moshe] Talpaz, [MD,] I started getting very involved with CML. In my initial years as a young faculty, I started working with him on interferon. Then imatinib appeared. I saw even from the phase 1 study how impressive the outcomes were in patients who had no response to anything and were in bad shape.”
Q: What CML medications have you worked on?
A: “I’ve been involved with all of them. Imatinib early on, then I led trials with dasatinib and nilotinib. Then, I led the registration trials of bosutinib and ponatinib. More recently, I was part of the development of asciminib.”
Q: What were some of the biggest challenges in CML research?
A: “We had an opportunity to do a lot of analysis about TKIs [tyrosine kinase inhibitors] when these were new drugs. It was a very steep curve of learning, how to monitor and manage side effects.
Then patients were starting to have resistance to two to three TKIs. Ponatinib came along, and it was an incredibly effective drug. But after it was approved, we started to recognize the occurrence of heart attacks and strokes.
That was unexpected and not something that was known for any TKI. It was a big challenge. The drug was taken off the market for some time, and trials were put on hold by the FDA [US Food and Drug Administration].
We scrambled to understand the mechanism of action. For a year or two, it was a stressful time. But eventually we moved past it, and we learned a lot.”
Q: What sort of work have you done in Latin America?
A: “I’ve always been very close to Latin America. I have many good friends and colleagues there, and I’ve always been interested in working with them.
We’ve done research and studies and created an organization called Latin American Leukemia Net to develop more trials in Latin America. The most rewarding thing has been the educational programs for patients that we’ve done, helping them understand the disease, the treatments, and the goals of treatment.
We’ve conducted a number of programs, and they have been effective, well-attended, and well received. I still work with my colleagues to develop local guidelines and do collaborative research.”
Q: What convinced you to leave MD Anderson for Georgia?
A: “I never thought I’d leave MD Anderson. I had my well-oiled machine of clinical trials, my clinic, and my fellowship program. But the one thing that I wanted to see if I could try next was to develop an institution.
That was the goal here, to take the Georgia Cancer Center to NCI [National Cancer Institute] designation. So, I thought, ‘That’s a nice challenge.’ It may be a good opportunity to try a different aspect of what it means to be an oncologist.
There are days that you think, ‘What am I doing here?’ when you have to deal with budgets and personnel and all these things. But it’s part of the process. It’s still good to know that we have a goal, and that we’re going to make it.
Also, I still see my patients, and I enjoy that I still do some research and mentoring.”
Q: What’s the current state of CML treatment?
A: “Many patients have a pretty much normal life expectancy while [on therapy]. Still, one of the goals of many patients is to stop therapy. But that’s a reality only for a small percentage of patients. How can we make that happen for more patients?”
Q: By stopping therapy, do you mean curing the cancer?
A: “Yes, pretty much. You have a good response, you stop the therapy, and it doesn’t come back.
There are also patients who really don’t do well. We hear about CML being with a disease with such a good outcome, but we have patients for whom nothing works. Is it a matter of [needing] another TKI, or do we need to look at something else?”
Q: What do you see on the horizon?
A: “We are developing new approaches like combination therapies. We’re scratching the surface on that. We need to understand which combinations work, and where and when.
And we can make more efficient uses of the drugs we have now in terms of which ones to use when, the doses, the safety profiles. I think we can do better.”
Cortes disclosed consulting for Amphivena, Astellas, Bio-Path, BioLineRx, Bristol Myers Squibb, Daiichi Sankyo, Jazz, Novartis, Pfizer, and Takeda and research funding from Astellas Pharma, Bristol Myers Squibb, Daiichi Sankyo, Immunogen, Jazz, Merus, Novartis, Pfizer, Sun Pharma, Takeda, Tolero and Trovagene.
A version of this article appeared on Medscape.com.
His work has helped transform CML into an often-survivable disease instead of one that took the lives of most patients within 5 years.
“It’s been remarkable to see the evolution in CML and to be part of that transition as a fellow, as faculty, and as leader of some of the trials,” said Cortes, who directs the Georgia Cancer Center at Augusta University. “I’m the luckiest person in the world.”
In an interview, Cortes talked about his youth in Mexico, his research path, and his close connections to cancer medicine in Latin America.
Q: You grew up in Mexico City. What was your family like?
A: “My father grew up very poor in a small town in Michoacán in the southwest part of Mexico. In Mexico City, he had a tiny grocery store in an old-fashioned market, and we were lower middle class.
One of the things I learned was to work hard. There’s nobody I know who worked as hard as my father. He opened his store every day of the year, [Mexican] Independence Day or New Year’s or Christmas. He worked hard so we could have a better life than he did.
We learned English from a very young age. My elementary school was called Westminster School because he wanted a school where we would learn English.
As for my mother, she stayed with us [at home] and made sure we did our homework and were taken care of. I learned about being honest and dedicating to what you were doing.”
Q: You trained at the Salvador Zubirán National Institute of Health Sciences and Nutrition in Mexico City. Then what happened?
A: “Through encouragement by my dermatologist older brother and a mentor at the institution where I was training as a hematologist, I decided to come to the United States.
My initial focus was going to be on coagulation and thrombosis. I came to Houston (Texas) for a fellowship at the University of Texas Health Science Center.
Then I started doing my rotation for the malignant part of the fellowship at MD Anderson Cancer Center [Houston]. One of my first rotations was with Susan M. O’Brien, [MD,] who became my greatest mentor throughout my career. I really enjoyed my rotation. I thought she was great clinically, and she was doing research and teaching. That’s what I wanted for my career.”
Q: What drew you to leukemia specifically?
A: “Dr O’Brien worked in leukemia during my initial rotation, and I really loved it. It was hard work, but it was very inspiring to see the clinical research and the things you could for patients. She had a lot of joy doing that.
I told my program director I’d change and transfer to MD Anderson, and I ended up staying at MD Anderson for 23 years.”
Q: What was leukemia research like in those days?
A: “We didn’t have the understanding of the biology and the new drugs that we have now. When I started in Mexico, we didn’t even have hydroxyurea. What we were doing was much more basic. But still, the field sounded like a great field to be involved with because they were doing so many trials and had an outstanding database.
Because of the influence of Dr [Moshe] Talpaz, [MD,] I started getting very involved with CML. In my initial years as a young faculty, I started working with him on interferon. Then imatinib appeared. I saw even from the phase 1 study how impressive the outcomes were in patients who had no response to anything and were in bad shape.”
Q: What CML medications have you worked on?
A: “I’ve been involved with all of them. Imatinib early on, then I led trials with dasatinib and nilotinib. Then, I led the registration trials of bosutinib and ponatinib. More recently, I was part of the development of asciminib.”
Q: What were some of the biggest challenges in CML research?
A: “We had an opportunity to do a lot of analysis about TKIs [tyrosine kinase inhibitors] when these were new drugs. It was a very steep curve of learning, how to monitor and manage side effects.
Then patients were starting to have resistance to two to three TKIs. Ponatinib came along, and it was an incredibly effective drug. But after it was approved, we started to recognize the occurrence of heart attacks and strokes.
That was unexpected and not something that was known for any TKI. It was a big challenge. The drug was taken off the market for some time, and trials were put on hold by the FDA [US Food and Drug Administration].
We scrambled to understand the mechanism of action. For a year or two, it was a stressful time. But eventually we moved past it, and we learned a lot.”
Q: What sort of work have you done in Latin America?
A: “I’ve always been very close to Latin America. I have many good friends and colleagues there, and I’ve always been interested in working with them.
We’ve done research and studies and created an organization called Latin American Leukemia Net to develop more trials in Latin America. The most rewarding thing has been the educational programs for patients that we’ve done, helping them understand the disease, the treatments, and the goals of treatment.
We’ve conducted a number of programs, and they have been effective, well-attended, and well received. I still work with my colleagues to develop local guidelines and do collaborative research.”
Q: What convinced you to leave MD Anderson for Georgia?
A: “I never thought I’d leave MD Anderson. I had my well-oiled machine of clinical trials, my clinic, and my fellowship program. But the one thing that I wanted to see if I could try next was to develop an institution.
That was the goal here, to take the Georgia Cancer Center to NCI [National Cancer Institute] designation. So, I thought, ‘That’s a nice challenge.’ It may be a good opportunity to try a different aspect of what it means to be an oncologist.
There are days that you think, ‘What am I doing here?’ when you have to deal with budgets and personnel and all these things. But it’s part of the process. It’s still good to know that we have a goal, and that we’re going to make it.
Also, I still see my patients, and I enjoy that I still do some research and mentoring.”
Q: What’s the current state of CML treatment?
A: “Many patients have a pretty much normal life expectancy while [on therapy]. Still, one of the goals of many patients is to stop therapy. But that’s a reality only for a small percentage of patients. How can we make that happen for more patients?”
Q: By stopping therapy, do you mean curing the cancer?
A: “Yes, pretty much. You have a good response, you stop the therapy, and it doesn’t come back.
There are also patients who really don’t do well. We hear about CML being with a disease with such a good outcome, but we have patients for whom nothing works. Is it a matter of [needing] another TKI, or do we need to look at something else?”
Q: What do you see on the horizon?
A: “We are developing new approaches like combination therapies. We’re scratching the surface on that. We need to understand which combinations work, and where and when.
And we can make more efficient uses of the drugs we have now in terms of which ones to use when, the doses, the safety profiles. I think we can do better.”
Cortes disclosed consulting for Amphivena, Astellas, Bio-Path, BioLineRx, Bristol Myers Squibb, Daiichi Sankyo, Jazz, Novartis, Pfizer, and Takeda and research funding from Astellas Pharma, Bristol Myers Squibb, Daiichi Sankyo, Immunogen, Jazz, Merus, Novartis, Pfizer, Sun Pharma, Takeda, Tolero and Trovagene.
A version of this article appeared on Medscape.com.
Registered Dieticians Sparse in VA Cancer Care
Veterans Health Administration cancer centers are lacking registered dieticians (RDs), and patients are more likely to be diagnosed with malnutrition when they are on staff, according to a new study.
The average number of full-time RDs across 13 cancer centers was just 1 per 1,065 patients, advanced practice oncology dietitian Katherine Petersen, MS, RDN, CSO, of the Phoenix VA Health Care System, reported at the AVAHO annual meeting.
However, patients treated by RDs were more likely to be diagnosed with malnutrition (odds ratio [OR], 2.9, 95% CI, 1.6-5.1). And patients were more likely to maintain weight if their clinic had a higher ratio of RDs to oncologists (OR, 1.6 for each 10% increase in ratio, 95% CI, 2.0-127.5).
Petersen told Federal Practitioner that dieticians came up with the idea for the study after attending AVAHO meetings. “A lot of the questions we were getting from physicians and other providers were: How do we get dietitians in our clinic?”
There is currently no standard staffing model for dieticians in oncology centers, Petersen said, and they are not reimbursed through Medicare or Medicaid. “We thought, ‘What do we add to the cancer center by having adequate staffing levels and seeing cancer patients?’ We designed a study to try and get to the heart of that.”
Petersen and her team focused on malnutrition. Nutrition impairment impacts an estimated 40% to 80% of patients with gastrointestinal, head and neck, pancreas, and colorectal cancer at diagnosis, she said.
Petersen discussed the published evidence that outlines how physicians recognize malnutrition at a lower rate than RDs. Dietary counseling from an RD is linked to better nutritional outcomes, physical function, and quality of life.
The study authors examined 2016 and 2017 VA registry data and reviewed charts of 681 veterans treated by 207 oncologists. Oncology clinics had a mean of 0.5 full-time equivalent (FTE) RD. The mean ratio of full-time RDs to oncologists was 1 per 48.5 and ranged from 1 per 4 to 1 per 850.
“It's almost like somebody randomly assigned [RDs] to cancer centers, and it has nothing to do with how many patients are seen in that particular center,” Petersen said. “Some clinics only have .1 or .2 FTEs assigned, and that may be a larger cancer center where they have maybe 85 cancer oncology providers, which includes surgical, medical, and radiation oncology and trainees.”
Why would a clinic have a .1 FTE RD, which suggests someone may be working 4 hours a week? In this kind of situation, an RD may cover a variety of areas and only work in cancer care when they receive a referral, Petersen said.
“That is just vastly underserving veterans,” she said. “You're missing so many veterans whom you could help with preventative care if you're only getting patients referred based on consults.”
As for the findings regarding higher RD staffing and higher detection of malnutrition, the study text notes “there was not a ‘high enough’ level of RD staffing at which we stopped seeing this trend. This is probably because – at least at the time of this study – no VA cancer center was adequately staffed for nutrition.”
Petersen hopes the findings will convince VA cancer center leadership to boost better patient outcomes by prioritizing the hiring of RDs.
Katherine Petersen, MS, RDN, CSO has no disclosures.
Veterans Health Administration cancer centers are lacking registered dieticians (RDs), and patients are more likely to be diagnosed with malnutrition when they are on staff, according to a new study.
The average number of full-time RDs across 13 cancer centers was just 1 per 1,065 patients, advanced practice oncology dietitian Katherine Petersen, MS, RDN, CSO, of the Phoenix VA Health Care System, reported at the AVAHO annual meeting.
However, patients treated by RDs were more likely to be diagnosed with malnutrition (odds ratio [OR], 2.9, 95% CI, 1.6-5.1). And patients were more likely to maintain weight if their clinic had a higher ratio of RDs to oncologists (OR, 1.6 for each 10% increase in ratio, 95% CI, 2.0-127.5).
Petersen told Federal Practitioner that dieticians came up with the idea for the study after attending AVAHO meetings. “A lot of the questions we were getting from physicians and other providers were: How do we get dietitians in our clinic?”
There is currently no standard staffing model for dieticians in oncology centers, Petersen said, and they are not reimbursed through Medicare or Medicaid. “We thought, ‘What do we add to the cancer center by having adequate staffing levels and seeing cancer patients?’ We designed a study to try and get to the heart of that.”
Petersen and her team focused on malnutrition. Nutrition impairment impacts an estimated 40% to 80% of patients with gastrointestinal, head and neck, pancreas, and colorectal cancer at diagnosis, she said.
Petersen discussed the published evidence that outlines how physicians recognize malnutrition at a lower rate than RDs. Dietary counseling from an RD is linked to better nutritional outcomes, physical function, and quality of life.
The study authors examined 2016 and 2017 VA registry data and reviewed charts of 681 veterans treated by 207 oncologists. Oncology clinics had a mean of 0.5 full-time equivalent (FTE) RD. The mean ratio of full-time RDs to oncologists was 1 per 48.5 and ranged from 1 per 4 to 1 per 850.
“It's almost like somebody randomly assigned [RDs] to cancer centers, and it has nothing to do with how many patients are seen in that particular center,” Petersen said. “Some clinics only have .1 or .2 FTEs assigned, and that may be a larger cancer center where they have maybe 85 cancer oncology providers, which includes surgical, medical, and radiation oncology and trainees.”
Why would a clinic have a .1 FTE RD, which suggests someone may be working 4 hours a week? In this kind of situation, an RD may cover a variety of areas and only work in cancer care when they receive a referral, Petersen said.
“That is just vastly underserving veterans,” she said. “You're missing so many veterans whom you could help with preventative care if you're only getting patients referred based on consults.”
As for the findings regarding higher RD staffing and higher detection of malnutrition, the study text notes “there was not a ‘high enough’ level of RD staffing at which we stopped seeing this trend. This is probably because – at least at the time of this study – no VA cancer center was adequately staffed for nutrition.”
Petersen hopes the findings will convince VA cancer center leadership to boost better patient outcomes by prioritizing the hiring of RDs.
Katherine Petersen, MS, RDN, CSO has no disclosures.
Veterans Health Administration cancer centers are lacking registered dieticians (RDs), and patients are more likely to be diagnosed with malnutrition when they are on staff, according to a new study.
The average number of full-time RDs across 13 cancer centers was just 1 per 1,065 patients, advanced practice oncology dietitian Katherine Petersen, MS, RDN, CSO, of the Phoenix VA Health Care System, reported at the AVAHO annual meeting.
However, patients treated by RDs were more likely to be diagnosed with malnutrition (odds ratio [OR], 2.9, 95% CI, 1.6-5.1). And patients were more likely to maintain weight if their clinic had a higher ratio of RDs to oncologists (OR, 1.6 for each 10% increase in ratio, 95% CI, 2.0-127.5).
Petersen told Federal Practitioner that dieticians came up with the idea for the study after attending AVAHO meetings. “A lot of the questions we were getting from physicians and other providers were: How do we get dietitians in our clinic?”
There is currently no standard staffing model for dieticians in oncology centers, Petersen said, and they are not reimbursed through Medicare or Medicaid. “We thought, ‘What do we add to the cancer center by having adequate staffing levels and seeing cancer patients?’ We designed a study to try and get to the heart of that.”
Petersen and her team focused on malnutrition. Nutrition impairment impacts an estimated 40% to 80% of patients with gastrointestinal, head and neck, pancreas, and colorectal cancer at diagnosis, she said.
Petersen discussed the published evidence that outlines how physicians recognize malnutrition at a lower rate than RDs. Dietary counseling from an RD is linked to better nutritional outcomes, physical function, and quality of life.
The study authors examined 2016 and 2017 VA registry data and reviewed charts of 681 veterans treated by 207 oncologists. Oncology clinics had a mean of 0.5 full-time equivalent (FTE) RD. The mean ratio of full-time RDs to oncologists was 1 per 48.5 and ranged from 1 per 4 to 1 per 850.
“It's almost like somebody randomly assigned [RDs] to cancer centers, and it has nothing to do with how many patients are seen in that particular center,” Petersen said. “Some clinics only have .1 or .2 FTEs assigned, and that may be a larger cancer center where they have maybe 85 cancer oncology providers, which includes surgical, medical, and radiation oncology and trainees.”
Why would a clinic have a .1 FTE RD, which suggests someone may be working 4 hours a week? In this kind of situation, an RD may cover a variety of areas and only work in cancer care when they receive a referral, Petersen said.
“That is just vastly underserving veterans,” she said. “You're missing so many veterans whom you could help with preventative care if you're only getting patients referred based on consults.”
As for the findings regarding higher RD staffing and higher detection of malnutrition, the study text notes “there was not a ‘high enough’ level of RD staffing at which we stopped seeing this trend. This is probably because – at least at the time of this study – no VA cancer center was adequately staffed for nutrition.”
Petersen hopes the findings will convince VA cancer center leadership to boost better patient outcomes by prioritizing the hiring of RDs.
Katherine Petersen, MS, RDN, CSO has no disclosures.