Randy Dotinga

Patient outcomes could be threatened because of misinterpretation by oncologic surgeons of free-form posttreatment radiological reports in head and neck squamous cell carcinoma (HNSCC), a new study finds.

“Clinician perception of patient response from the post-RT [radiation treament] PET/CT free-form report is unreliable and does not consistently reflect the radiologist’s intended meaning, which was strongly associated with survival,” researchers wrote in a study published Aug. 18 in JAMA Otolaryngology-Head & Neck Surgery. They found “minimal agreement between clinicians’ consensus perspective on the patient’s response status derived from free-form imaging reports and the criterion standard response category assigned by a nuclear medicine specialist after PET/CT image review.”

According to radiation oncologist Ryan T. Hughes, MD, and colleagues at Wake Forest University, Winston-Salem, N.C., it’s common for patients with HNSCC to get PET, CT, or PET/CT imaging following treatment in order to assess how patients responded. Accurate communication about the results is essential to determining next steps, they write.

However, they write, “to our knowledge there is no universally accepted standardized method for communicating results,” such as whether there’s been a complete or partial response. Discrepancies between a radiological posttreatment report and an oncologist’s perception of the findings “may contribute to unnecessary patient care complexities, including elevated patient anxiety, unnecessary follow-up testing/procedures, and failure to recognize and adequately treat residual, recurrent, or progressive disease,” the researchers write.

For the new study, the authors tracked 171 patients (26.3% women, median age 61 years, ethnicity not provided), mainly (87%) with stage III-IV disease. Most (89%) received concurrent chemotherapy, and 30% received radiotherapy following operations.

Four oncologists reviewed free-form radiologic reports and determined whether the patient had a complete, indeterminate or partial response, or progressive disease. “Next, the group conferred to assign a consensus clinician MDS [modified Deauville score] and associated response category to assess the percentage of agreement with the criterion standard nuclear medicine physician MDS response derived from PET/CT image review.”

The researchers found that “interrater reliability of clinician-perceived post-RT PET/CT response was moderate [k = 0.680; 95% confidence interval, 0.638-0.721], and there was minimal reliability and low rate of agreement between clinician perception and radiologist-intended PET/CT response [63.7%; k = 0.365; 95% CI, 0.251-0.478).”

The clinicians were more likely to perceive patients as having an indeterminate response (28.1%), compared with the radiologists (9.3%). “There were 16 instances of significant discordance: 7 patients for whom the clinician perception MDS was 1 to 2 and nuclear medicine MDS 3 to 4, and 9 patients for whom the clinician perception MDS was 3 to 4 and nuclear medicine MDS 1 to 2.”

Due to statistical limitations, the researchers were unable to link the MDS scores to prognoses. The researchers suggest it’s time to further standardize the assessment of posttreatment responses to therapy. They add that “the decision to use a standardized interpretation and reporting system rather than free-form reporting is more important than the specific system selected.”

As for next steps, the researchers report that “prospective studies of post-RT PET/CT standardized reporting among patients with HNSCC are warranted, and a prospective implementation study of this workflow is planned at our institution.”

The study was funded by the National Center for Advancing Translational Sciences and National Institutes of Health. The authors had no disclosures.

Patient outcomes could be threatened because of misinterpretation by oncologic surgeons of free-form posttreatment radiological reports in head and neck squamous cell carcinoma (HNSCC), a new study finds.

“Clinician perception of patient response from the post-RT [radiation treament] PET/CT free-form report is unreliable and does not consistently reflect the radiologist’s intended meaning, which was strongly associated with survival,” researchers wrote in a study published Aug. 18 in JAMA Otolaryngology-Head & Neck Surgery. They found “minimal agreement between clinicians’ consensus perspective on the patient’s response status derived from free-form imaging reports and the criterion standard response category assigned by a nuclear medicine specialist after PET/CT image review.”

According to radiation oncologist Ryan T. Hughes, MD, and colleagues at Wake Forest University, Winston-Salem, N.C., it’s common for patients with HNSCC to get PET, CT, or PET/CT imaging following treatment in order to assess how patients responded. Accurate communication about the results is essential to determining next steps, they write.

However, they write, “to our knowledge there is no universally accepted standardized method for communicating results,” such as whether there’s been a complete or partial response. Discrepancies between a radiological posttreatment report and an oncologist’s perception of the findings “may contribute to unnecessary patient care complexities, including elevated patient anxiety, unnecessary follow-up testing/procedures, and failure to recognize and adequately treat residual, recurrent, or progressive disease,” the researchers write.

For the new study, the authors tracked 171 patients (26.3% women, median age 61 years, ethnicity not provided), mainly (87%) with stage III-IV disease. Most (89%) received concurrent chemotherapy, and 30% received radiotherapy following operations.

Four oncologists reviewed free-form radiologic reports and determined whether the patient had a complete, indeterminate or partial response, or progressive disease. “Next, the group conferred to assign a consensus clinician MDS [modified Deauville score] and associated response category to assess the percentage of agreement with the criterion standard nuclear medicine physician MDS response derived from PET/CT image review.”

The researchers found that “interrater reliability of clinician-perceived post-RT PET/CT response was moderate [k = 0.680; 95% confidence interval, 0.638-0.721], and there was minimal reliability and low rate of agreement between clinician perception and radiologist-intended PET/CT response [63.7%; k = 0.365; 95% CI, 0.251-0.478).”

The clinicians were more likely to perceive patients as having an indeterminate response (28.1%), compared with the radiologists (9.3%). “There were 16 instances of significant discordance: 7 patients for whom the clinician perception MDS was 1 to 2 and nuclear medicine MDS 3 to 4, and 9 patients for whom the clinician perception MDS was 3 to 4 and nuclear medicine MDS 1 to 2.”

Due to statistical limitations, the researchers were unable to link the MDS scores to prognoses. The researchers suggest it’s time to further standardize the assessment of posttreatment responses to therapy. They add that “the decision to use a standardized interpretation and reporting system rather than free-form reporting is more important than the specific system selected.”

As for next steps, the researchers report that “prospective studies of post-RT PET/CT standardized reporting among patients with HNSCC are warranted, and a prospective implementation study of this workflow is planned at our institution.”

The study was funded by the National Center for Advancing Translational Sciences and National Institutes of Health. The authors had no disclosures.

Patient outcomes could be threatened because of misinterpretation by oncologic surgeons of free-form posttreatment radiological reports in head and neck squamous cell carcinoma (HNSCC), a new study finds.

“Clinician perception of patient response from the post-RT [radiation treament] PET/CT free-form report is unreliable and does not consistently reflect the radiologist’s intended meaning, which was strongly associated with survival,” researchers wrote in a study published Aug. 18 in JAMA Otolaryngology-Head & Neck Surgery. They found “minimal agreement between clinicians’ consensus perspective on the patient’s response status derived from free-form imaging reports and the criterion standard response category assigned by a nuclear medicine specialist after PET/CT image review.”

According to radiation oncologist Ryan T. Hughes, MD, and colleagues at Wake Forest University, Winston-Salem, N.C., it’s common for patients with HNSCC to get PET, CT, or PET/CT imaging following treatment in order to assess how patients responded. Accurate communication about the results is essential to determining next steps, they write.

However, they write, “to our knowledge there is no universally accepted standardized method for communicating results,” such as whether there’s been a complete or partial response. Discrepancies between a radiological posttreatment report and an oncologist’s perception of the findings “may contribute to unnecessary patient care complexities, including elevated patient anxiety, unnecessary follow-up testing/procedures, and failure to recognize and adequately treat residual, recurrent, or progressive disease,” the researchers write.

For the new study, the authors tracked 171 patients (26.3% women, median age 61 years, ethnicity not provided), mainly (87%) with stage III-IV disease. Most (89%) received concurrent chemotherapy, and 30% received radiotherapy following operations.

Four oncologists reviewed free-form radiologic reports and determined whether the patient had a complete, indeterminate or partial response, or progressive disease. “Next, the group conferred to assign a consensus clinician MDS [modified Deauville score] and associated response category to assess the percentage of agreement with the criterion standard nuclear medicine physician MDS response derived from PET/CT image review.”

The researchers found that “interrater reliability of clinician-perceived post-RT PET/CT response was moderate [k = 0.680; 95% confidence interval, 0.638-0.721], and there was minimal reliability and low rate of agreement between clinician perception and radiologist-intended PET/CT response [63.7%; k = 0.365; 95% CI, 0.251-0.478).”

The clinicians were more likely to perceive patients as having an indeterminate response (28.1%), compared with the radiologists (9.3%). “There were 16 instances of significant discordance: 7 patients for whom the clinician perception MDS was 1 to 2 and nuclear medicine MDS 3 to 4, and 9 patients for whom the clinician perception MDS was 3 to 4 and nuclear medicine MDS 1 to 2.”

Due to statistical limitations, the researchers were unable to link the MDS scores to prognoses. The researchers suggest it’s time to further standardize the assessment of posttreatment responses to therapy. They add that “the decision to use a standardized interpretation and reporting system rather than free-form reporting is more important than the specific system selected.”

As for next steps, the researchers report that “prospective studies of post-RT PET/CT standardized reporting among patients with HNSCC are warranted, and a prospective implementation study of this workflow is planned at our institution.”

The study was funded by the National Center for Advancing Translational Sciences and National Institutes of Health. The authors had no disclosures.

A new study provides more evidence that people with thyroid autoimmunity are more likely than are others to develop papillary thyroid cancer (odds ratio [OR] = 1.90, 95% confidence interval [CI], 1.33-2.70), although the overall risk remains very low. 
Researchers aren't recommending routine screening in all patients with thyroid autoimmunity, but they're calling for more research into whether it's a good idea in severe cases. "This is the one circumstance where screening for subclinical disease could make sense," said Donald McLeod, MPH, PhD, an epidemiologist at Royal Brisbane & Women's Hospital in Australia and lead author of the study, published in the Journal of Clinical Oncology. "However, more research is needed because our study is the first to show this result, and we need to prove that screening would make a difference to the prognosis of these patients." 
According to Dr. McLeod, "doctors and patients have been wondering about the connection between thyroid autoimmunity and thyroid cancer for many years. In fact, the first report was in 1955. While the association was plausible, all previous studies had potential for biases that could have influenced the results." 
For example, he said, multiple studies didn't control for confounders, while others didn't account for the possibility that cancer could have triggered an immune response. "Other case-control studies could have been affected by selection bias, where a diagnosis of thyroid autoimmunity leads to thyroid cancer identification and entry into the study," he said. "Finally, medical surveillance of people diagnosed with thyroid autoimmunity could lead to overdiagnosis, where small, subclinical cancers are diagnosed in those patients but not identified in people who are not under medical follow-up." 
For the new retrospective case-control study, researchers compared 451 active-duty members of the U.S. military who developed papillary thyroid cancer from the period of 1996-2014 to matched controls (61% of all subjects were men and the mean age was 36). Those with cancer had their serum collected 3-5 years and 7-10 years before the date of diagnosis - the index date for all subjects. Some of those considered to have thyroid autoimmunity had conditions such as Graves' disease and Hashimoto's thyroiditis. 
"Eighty-five percent of cases (379 of 451) had a thyroid-related diagnosis recorded ... before their index date, compared with 5% of controls," the researchers reported. "Most cases (80%) had classical papillary thyroid cancer, with the rest having the follicular variant of papillary thyroid cancer."  
After adjustment to account for various confounders, those who were positive for thyroid peroxidase antibodies 7-10 years prior to the index date were more likely to have developed thyroid cancer (OR = 1.90, 95% CI, 1.33-2.70). "The results could not be fully explained by diagnosis of thyroid autoimmunity," the researchers reported, "although when autoimmunity had been identified, thyroid cancers were diagnosed at a very early stage." 
Two groups - those with the highest thyroid antibody levels and women - faced the greatest risk, Dr. McLeod said. The results regarding women were the most surprising in the study, he said. "This is the first time this has been found. We think this result needs to be confirmed. If true, it could explain why women have a three-times-higher risk of thyroid cancer than men." 
The overall incidence of thyroid cancer in the U.S. was estimated at 13.49 per 100,000 person-years in 2018, with women (76% of cases) and Whites (81%) accounting for the majority. Rates have nearly doubled since 2000. The authors of a 2022 report that disclosed these numbers suggest the rise is due to overdiagnosis of small tumors. 
It's not clear why thyroid autoimmunity and thyroid cancer may be linked. "Chronic inflammation from thyroid autoimmunity could cause thyroid cancer, as chronic inflammation in other organs precedes cancers at those sites," Dr. McLeod said. "Alternatively, thyroid autoimmunity could appear to be associated with thyroid cancer because of biases inherent in previous studies, including previous diagnosis of autoimmunity. Thyroid cancer could also induce an immune response, which mimics thyroid autoimmunity and could bias assessment." 
As for screening of patients with thyroid autoimmunity, "the main danger is that you will commonly identify small thyroid cancers that would never become clinically apparent," he said. "This leads to unnecessary treatments that can cause complications and give people a cancer label, which can also cause harm. Diagnosis and treatment guidelines recommend against screening the general population for this reason." 
Many of those with thyroid autoimmunity developed small cancers, he said, most likely "detected from ultrasound being performed because autoimmune thyroid disease was known. If all patients with thyroid autoimmunity were screened for thyroid cancer, the likelihood is that many people's cancers would be overdiagnosed." 
The study was funded by the Walton Family Foundation. Dr. McLeod reports no disclosures. Some of the authors report various relationships with industry.

A new study provides more evidence that people with thyroid autoimmunity are more likely than are others to develop papillary thyroid cancer (odds ratio [OR] = 1.90, 95% confidence interval [CI], 1.33-2.70), although the overall risk remains very low. 
Researchers aren't recommending routine screening in all patients with thyroid autoimmunity, but they're calling for more research into whether it's a good idea in severe cases. "This is the one circumstance where screening for subclinical disease could make sense," said Donald McLeod, MPH, PhD, an epidemiologist at Royal Brisbane & Women's Hospital in Australia and lead author of the study, published in the Journal of Clinical Oncology. "However, more research is needed because our study is the first to show this result, and we need to prove that screening would make a difference to the prognosis of these patients." 
According to Dr. McLeod, "doctors and patients have been wondering about the connection between thyroid autoimmunity and thyroid cancer for many years. In fact, the first report was in 1955. While the association was plausible, all previous studies had potential for biases that could have influenced the results." 
For example, he said, multiple studies didn't control for confounders, while others didn't account for the possibility that cancer could have triggered an immune response. "Other case-control studies could have been affected by selection bias, where a diagnosis of thyroid autoimmunity leads to thyroid cancer identification and entry into the study," he said. "Finally, medical surveillance of people diagnosed with thyroid autoimmunity could lead to overdiagnosis, where small, subclinical cancers are diagnosed in those patients but not identified in people who are not under medical follow-up." 
For the new retrospective case-control study, researchers compared 451 active-duty members of the U.S. military who developed papillary thyroid cancer from the period of 1996-2014 to matched controls (61% of all subjects were men and the mean age was 36). Those with cancer had their serum collected 3-5 years and 7-10 years before the date of diagnosis - the index date for all subjects. Some of those considered to have thyroid autoimmunity had conditions such as Graves' disease and Hashimoto's thyroiditis. 
"Eighty-five percent of cases (379 of 451) had a thyroid-related diagnosis recorded ... before their index date, compared with 5% of controls," the researchers reported. "Most cases (80%) had classical papillary thyroid cancer, with the rest having the follicular variant of papillary thyroid cancer."  
After adjustment to account for various confounders, those who were positive for thyroid peroxidase antibodies 7-10 years prior to the index date were more likely to have developed thyroid cancer (OR = 1.90, 95% CI, 1.33-2.70). "The results could not be fully explained by diagnosis of thyroid autoimmunity," the researchers reported, "although when autoimmunity had been identified, thyroid cancers were diagnosed at a very early stage." 
Two groups - those with the highest thyroid antibody levels and women - faced the greatest risk, Dr. McLeod said. The results regarding women were the most surprising in the study, he said. "This is the first time this has been found. We think this result needs to be confirmed. If true, it could explain why women have a three-times-higher risk of thyroid cancer than men." 
The overall incidence of thyroid cancer in the U.S. was estimated at 13.49 per 100,000 person-years in 2018, with women (76% of cases) and Whites (81%) accounting for the majority. Rates have nearly doubled since 2000. The authors of a 2022 report that disclosed these numbers suggest the rise is due to overdiagnosis of small tumors. 
It's not clear why thyroid autoimmunity and thyroid cancer may be linked. "Chronic inflammation from thyroid autoimmunity could cause thyroid cancer, as chronic inflammation in other organs precedes cancers at those sites," Dr. McLeod said. "Alternatively, thyroid autoimmunity could appear to be associated with thyroid cancer because of biases inherent in previous studies, including previous diagnosis of autoimmunity. Thyroid cancer could also induce an immune response, which mimics thyroid autoimmunity and could bias assessment." 
As for screening of patients with thyroid autoimmunity, "the main danger is that you will commonly identify small thyroid cancers that would never become clinically apparent," he said. "This leads to unnecessary treatments that can cause complications and give people a cancer label, which can also cause harm. Diagnosis and treatment guidelines recommend against screening the general population for this reason." 
Many of those with thyroid autoimmunity developed small cancers, he said, most likely "detected from ultrasound being performed because autoimmune thyroid disease was known. If all patients with thyroid autoimmunity were screened for thyroid cancer, the likelihood is that many people's cancers would be overdiagnosed." 
The study was funded by the Walton Family Foundation. Dr. McLeod reports no disclosures. Some of the authors report various relationships with industry.

A new study provides more evidence that people with thyroid autoimmunity are more likely than are others to develop papillary thyroid cancer (odds ratio [OR] = 1.90, 95% confidence interval [CI], 1.33-2.70), although the overall risk remains very low. 
Researchers aren't recommending routine screening in all patients with thyroid autoimmunity, but they're calling for more research into whether it's a good idea in severe cases. "This is the one circumstance where screening for subclinical disease could make sense," said Donald McLeod, MPH, PhD, an epidemiologist at Royal Brisbane & Women's Hospital in Australia and lead author of the study, published in the Journal of Clinical Oncology. "However, more research is needed because our study is the first to show this result, and we need to prove that screening would make a difference to the prognosis of these patients." 
According to Dr. McLeod, "doctors and patients have been wondering about the connection between thyroid autoimmunity and thyroid cancer for many years. In fact, the first report was in 1955. While the association was plausible, all previous studies had potential for biases that could have influenced the results." 
For example, he said, multiple studies didn't control for confounders, while others didn't account for the possibility that cancer could have triggered an immune response. "Other case-control studies could have been affected by selection bias, where a diagnosis of thyroid autoimmunity leads to thyroid cancer identification and entry into the study," he said. "Finally, medical surveillance of people diagnosed with thyroid autoimmunity could lead to overdiagnosis, where small, subclinical cancers are diagnosed in those patients but not identified in people who are not under medical follow-up." 
For the new retrospective case-control study, researchers compared 451 active-duty members of the U.S. military who developed papillary thyroid cancer from the period of 1996-2014 to matched controls (61% of all subjects were men and the mean age was 36). Those with cancer had their serum collected 3-5 years and 7-10 years before the date of diagnosis - the index date for all subjects. Some of those considered to have thyroid autoimmunity had conditions such as Graves' disease and Hashimoto's thyroiditis. 
"Eighty-five percent of cases (379 of 451) had a thyroid-related diagnosis recorded ... before their index date, compared with 5% of controls," the researchers reported. "Most cases (80%) had classical papillary thyroid cancer, with the rest having the follicular variant of papillary thyroid cancer."  
After adjustment to account for various confounders, those who were positive for thyroid peroxidase antibodies 7-10 years prior to the index date were more likely to have developed thyroid cancer (OR = 1.90, 95% CI, 1.33-2.70). "The results could not be fully explained by diagnosis of thyroid autoimmunity," the researchers reported, "although when autoimmunity had been identified, thyroid cancers were diagnosed at a very early stage." 
Two groups - those with the highest thyroid antibody levels and women - faced the greatest risk, Dr. McLeod said. The results regarding women were the most surprising in the study, he said. "This is the first time this has been found. We think this result needs to be confirmed. If true, it could explain why women have a three-times-higher risk of thyroid cancer than men." 
The overall incidence of thyroid cancer in the U.S. was estimated at 13.49 per 100,000 person-years in 2018, with women (76% of cases) and Whites (81%) accounting for the majority. Rates have nearly doubled since 2000. The authors of a 2022 report that disclosed these numbers suggest the rise is due to overdiagnosis of small tumors. 
It's not clear why thyroid autoimmunity and thyroid cancer may be linked. "Chronic inflammation from thyroid autoimmunity could cause thyroid cancer, as chronic inflammation in other organs precedes cancers at those sites," Dr. McLeod said. "Alternatively, thyroid autoimmunity could appear to be associated with thyroid cancer because of biases inherent in previous studies, including previous diagnosis of autoimmunity. Thyroid cancer could also induce an immune response, which mimics thyroid autoimmunity and could bias assessment." 
As for screening of patients with thyroid autoimmunity, "the main danger is that you will commonly identify small thyroid cancers that would never become clinically apparent," he said. "This leads to unnecessary treatments that can cause complications and give people a cancer label, which can also cause harm. Diagnosis and treatment guidelines recommend against screening the general population for this reason." 
Many of those with thyroid autoimmunity developed small cancers, he said, most likely "detected from ultrasound being performed because autoimmune thyroid disease was known. If all patients with thyroid autoimmunity were screened for thyroid cancer, the likelihood is that many people's cancers would be overdiagnosed." 
The study was funded by the Walton Family Foundation. Dr. McLeod reports no disclosures. Some of the authors report various relationships with industry.

An international team of researchers have developed a “molecular map” of chronic lymphocytic leukemia (CLL) and used it to refine genetic subtypes and variations that appear to be linked to clinical outcomes.

Released in a report in Nature Genetics, the map has doubled the number of genetic traits linked the disease from around 100 to 202, lead author Binyamin A. Knisbacher, PhD, a postdoctoral fellow at the Broad Institute of MIT and Harvard Medical Schoo, Boston, said in an interview.

“It also delineated the molecular landscape of the two immunoglobulin gene (IGHV) subtypes, refined CLL subtyping, and built richer genetic prognostic models,” he said.

According to Dr. Knisbacher, CLL “has been at the forefront of genomic discovery,” and research has shown that there’s a wide variety of somatic mutations that drive CLL initiation across the patient population. However, as many as 10% of cases don’t appear to be driven by any known genetic variation, he said, and there’s a need to identify more subtypes and “build richer prognostic models of patient survival” based on genetics and multiomics such as genomics, transcriptomics, and epigenomics.

For the new study, researchers analyzed RNA and DNA from 1,095 patients with CLL and 54 patients with monoclonal B cell lymphocytosis and built what they say is the largest CLL dataset in existence. It’s twice the size of previous datasets, Dr. Knisbacher said.

“We found that RNA expression data was extremely informative for characterizing CLL,” Dr. Knisbacher said. “The RNA expression subtypes refined the ‘classic’ two IGHV subtypes. It is well documented that patients with U-CLL (IGHV-unmutated CLL) have substantially worse clinical outcome in comparison to M-CLL patients (IGHV-mutated CLLs). We found that M-CLLs that have RNA expression profiles similar to U-CLLs have worse survival than M-CLLs with a typical expression profile. Failure-free survival was 50% shorter – 5.3 versus 10.7 years median failure-free survival.”

In addition, he said, “U-CLLs with expression similar to M-CLLs had better survival than U-CLLs with an RNA expression profile typical to U-CLLs.”

The researchers have made their molecular map publicly available at https://cllmap.org/. Researchers can use it “to discover more about each subtype of CLL, and these future studies can help to improve clinical prognosis for the benefit of the patient,” Dr. Knisbacher said.

The study authors added that “this molecular foundation may allow for better prediction of response to therapy or provide the basis for rational combination of novel agents.”

Lee Greenberger, PhD, chief science officer of the Leukemia & Lymphoma Society, said in an interview that the study “provides foundational data further subtyping CLL patients and outcomes. It identifies new targets for therapy or diagnostic predictions in the future. This type of foundational work has proven invaluable in the development of new medicines for cancer in general.”

While there are many medications that have improved therapeutic outcomes in CLL, he added, “cures – or life-long disease control –remain elusive for many patients. Therefore, new molecular insights are needed that could personalize therapies or even lead to entirely new therapies.”

In addition, he said, although prevention of CLL still remains elusive, “it is conceivable that some of the mutations found in this paper occur early in the CLL trajectory, perhaps even before the disease is presented clinically.”

The study was funded by the National Institutes of Health and the Broad/IBM Cancer Resistance Research Project. Dr. Knisbacher and several other authors disclose that they are inventors on a patent related to CLL. Several authors report various relationships with industry. Dr. Greenberger has no disclosures.
 

An international team of researchers have developed a “molecular map” of chronic lymphocytic leukemia (CLL) and used it to refine genetic subtypes and variations that appear to be linked to clinical outcomes.

Released in a report in Nature Genetics, the map has doubled the number of genetic traits linked the disease from around 100 to 202, lead author Binyamin A. Knisbacher, PhD, a postdoctoral fellow at the Broad Institute of MIT and Harvard Medical Schoo, Boston, said in an interview.

“It also delineated the molecular landscape of the two immunoglobulin gene (IGHV) subtypes, refined CLL subtyping, and built richer genetic prognostic models,” he said.

According to Dr. Knisbacher, CLL “has been at the forefront of genomic discovery,” and research has shown that there’s a wide variety of somatic mutations that drive CLL initiation across the patient population. However, as many as 10% of cases don’t appear to be driven by any known genetic variation, he said, and there’s a need to identify more subtypes and “build richer prognostic models of patient survival” based on genetics and multiomics such as genomics, transcriptomics, and epigenomics.

For the new study, researchers analyzed RNA and DNA from 1,095 patients with CLL and 54 patients with monoclonal B cell lymphocytosis and built what they say is the largest CLL dataset in existence. It’s twice the size of previous datasets, Dr. Knisbacher said.

“We found that RNA expression data was extremely informative for characterizing CLL,” Dr. Knisbacher said. “The RNA expression subtypes refined the ‘classic’ two IGHV subtypes. It is well documented that patients with U-CLL (IGHV-unmutated CLL) have substantially worse clinical outcome in comparison to M-CLL patients (IGHV-mutated CLLs). We found that M-CLLs that have RNA expression profiles similar to U-CLLs have worse survival than M-CLLs with a typical expression profile. Failure-free survival was 50% shorter – 5.3 versus 10.7 years median failure-free survival.”

In addition, he said, “U-CLLs with expression similar to M-CLLs had better survival than U-CLLs with an RNA expression profile typical to U-CLLs.”

The researchers have made their molecular map publicly available at https://cllmap.org/. Researchers can use it “to discover more about each subtype of CLL, and these future studies can help to improve clinical prognosis for the benefit of the patient,” Dr. Knisbacher said.

The study authors added that “this molecular foundation may allow for better prediction of response to therapy or provide the basis for rational combination of novel agents.”

Lee Greenberger, PhD, chief science officer of the Leukemia & Lymphoma Society, said in an interview that the study “provides foundational data further subtyping CLL patients and outcomes. It identifies new targets for therapy or diagnostic predictions in the future. This type of foundational work has proven invaluable in the development of new medicines for cancer in general.”

While there are many medications that have improved therapeutic outcomes in CLL, he added, “cures – or life-long disease control –remain elusive for many patients. Therefore, new molecular insights are needed that could personalize therapies or even lead to entirely new therapies.”

In addition, he said, although prevention of CLL still remains elusive, “it is conceivable that some of the mutations found in this paper occur early in the CLL trajectory, perhaps even before the disease is presented clinically.”

The study was funded by the National Institutes of Health and the Broad/IBM Cancer Resistance Research Project. Dr. Knisbacher and several other authors disclose that they are inventors on a patent related to CLL. Several authors report various relationships with industry. Dr. Greenberger has no disclosures.
 

An international team of researchers have developed a “molecular map” of chronic lymphocytic leukemia (CLL) and used it to refine genetic subtypes and variations that appear to be linked to clinical outcomes.

Released in a report in Nature Genetics, the map has doubled the number of genetic traits linked the disease from around 100 to 202, lead author Binyamin A. Knisbacher, PhD, a postdoctoral fellow at the Broad Institute of MIT and Harvard Medical Schoo, Boston, said in an interview.

“It also delineated the molecular landscape of the two immunoglobulin gene (IGHV) subtypes, refined CLL subtyping, and built richer genetic prognostic models,” he said.

According to Dr. Knisbacher, CLL “has been at the forefront of genomic discovery,” and research has shown that there’s a wide variety of somatic mutations that drive CLL initiation across the patient population. However, as many as 10% of cases don’t appear to be driven by any known genetic variation, he said, and there’s a need to identify more subtypes and “build richer prognostic models of patient survival” based on genetics and multiomics such as genomics, transcriptomics, and epigenomics.

For the new study, researchers analyzed RNA and DNA from 1,095 patients with CLL and 54 patients with monoclonal B cell lymphocytosis and built what they say is the largest CLL dataset in existence. It’s twice the size of previous datasets, Dr. Knisbacher said.

“We found that RNA expression data was extremely informative for characterizing CLL,” Dr. Knisbacher said. “The RNA expression subtypes refined the ‘classic’ two IGHV subtypes. It is well documented that patients with U-CLL (IGHV-unmutated CLL) have substantially worse clinical outcome in comparison to M-CLL patients (IGHV-mutated CLLs). We found that M-CLLs that have RNA expression profiles similar to U-CLLs have worse survival than M-CLLs with a typical expression profile. Failure-free survival was 50% shorter – 5.3 versus 10.7 years median failure-free survival.”

In addition, he said, “U-CLLs with expression similar to M-CLLs had better survival than U-CLLs with an RNA expression profile typical to U-CLLs.”

The researchers have made their molecular map publicly available at https://cllmap.org/. Researchers can use it “to discover more about each subtype of CLL, and these future studies can help to improve clinical prognosis for the benefit of the patient,” Dr. Knisbacher said.

The study authors added that “this molecular foundation may allow for better prediction of response to therapy or provide the basis for rational combination of novel agents.”

Lee Greenberger, PhD, chief science officer of the Leukemia & Lymphoma Society, said in an interview that the study “provides foundational data further subtyping CLL patients and outcomes. It identifies new targets for therapy or diagnostic predictions in the future. This type of foundational work has proven invaluable in the development of new medicines for cancer in general.”

While there are many medications that have improved therapeutic outcomes in CLL, he added, “cures – or life-long disease control –remain elusive for many patients. Therefore, new molecular insights are needed that could personalize therapies or even lead to entirely new therapies.”

In addition, he said, although prevention of CLL still remains elusive, “it is conceivable that some of the mutations found in this paper occur early in the CLL trajectory, perhaps even before the disease is presented clinically.”

The study was funded by the National Institutes of Health and the Broad/IBM Cancer Resistance Research Project. Dr. Knisbacher and several other authors disclose that they are inventors on a patent related to CLL. Several authors report various relationships with industry. Dr. Greenberger has no disclosures.
 

Two new studies offer insights into leukemia survival rates in the United States. From 2000 to 2014, a drop in mortality among children spurred a rise in 5-year leukemia survival rates among patients aged 0-24. But adolescents and young adults who survive 5 years after diagnosis face an ongoing higher risk of death, recent research revealed, and their long-term survival is lower compared to that of the general population.

“Outcomes are improving. However, additional efforts, support, and resources are needed to further improve short- and long-term survival for acute leukemia survivors. Targeted efforts focused on populations that face greater disparities in their survival are needed to move the needle faster,” Michael Roth, MD, codirector of the Adolescent and Young Adult Oncology Program at the University of Texas M.D. Anderson Cancer Center, said in an interview.

In one study, released in The Lancet Child & Adolescent Health, an international team of researchers tracked survival outcomes from various types of leukemia in 61 nations. The study focused on the years 2000-2014 and followed patients aged 0-24.

“Age-standardized 5-year net survival in children, adolescents, and young adults for all leukemias combined during 2010-14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia,” the researchers wrote. “Throughout 2000-14, survival from all leukemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries.”

The U.S. data came from 41 states that cover 86% of the nation’s population, lead author Naomi Ssenyonga, a research fellow at London School of Hygiene & Tropical Medicine, said in an interview.

The 5-year survival rate for acute lymphoid leukemia (ALL) rose from 80% during 2000-2004 to 86% during 2010-2014. Survival in patients with acute myeloid leukemia (AML) was lower than for other subtypes: 66% in 2010-2014 vs. 57% in 2000-2004.

In regard to all leukemias, “we noted a steady increase in the U.S. of 6 percentage points in 5-year survival, up from 77% for patients diagnosed during 2000-2004 to 83% for those diagnosed during 2010-2014,” Ms. Ssenyonga said. “The gains were largely driven by the improvements seen among children.”

Why haven’t adolescents and young adults gained as much ground in survival?

“They often have unique clinical needs,” Ms. Ssenyonga said. “Over the past few years, adolescents and young adults with leukemia in some parts of the world, including the U.S., have increasingly been treated under pediatric protocols. This has led to higher survival. However, this approach has not been adopted consistently, and survival for adolescents and young adults with leukemia is still generally lower than survival for children.”

Gwen Nichols, MD, chief medical officer of the Leukemia & Lymphoma Society, agreed that pediatric treatment protocols hold promise as treatments for young adults. However, “because we arbitrarily set an age cutoff for being an adult, many of these patients are treated by an adult [nonpediatric] hematologist/oncologist, and some patients in the 20-39 age group do not receive the more intensive treatment regimens given to children,” she said in an interview.

In another study, published in Cancer Epidemiology, Biomarkers, & Prevention, M.D. Anderson Cancer Center’s Dr. Roth and colleagues tracked 1,938 patients with ALL and 2,350 with AML who were diagnosed at ages 15-39 from 1980 to 2009. All lived at least 5 years after diagnosis. In both groups, about 58% were White, and most of the rest were Hispanic. The median age of diagnosis for ALL was 23 (range: 15-39) and 28 years for AML (range: 15-39).

“For ALL, 10-year survival for those diagnosed in the 1980s, 1990s, and 2000s was 83%, 88%, and 88%, respectively,” the researchers reported. “Ten-year survival for AML was 82%, 90%, and 90% for those diagnosed in the 1980s, 1990s, and 2000s, respectively.”

“Early mortality within 10 years of diagnosis was mostly secondary to leukemia progressing or recurring. We believe that later mortality is secondary to the development of late side effects from their cancer treatment,” Dr. Roth said.

He noted that many adolescents and young adults with ALL or AML receive stem-cell transplants. “This treatment approach is effective. However, it is associated with short- and long-term toxicity that impacts patients’ health for many years after treatment.”

Indeed, up to 80% of acute leukemia survivors have significant health complications after therapy, said the Leukemia & Lymphoma Society’s Dr. Nichols, who wasn’t surprised by the findings. According to the society, “even when treatments are effective, more than 70% of childhood cancer survivors have a chronic health condition and 42% have a severe, disabling or life-threatening condition 30 years after diagnosis.”

“It would be interesting to understand the male predominance better,” she added, noting that the study found that male patients had worse long-term survival than females (survival time ratio: 0.61, 95% confidence interval, 0.45-0.82). “While it is tempting to suggest it is due to difference in cardiac disease, I am not aware of data to support why there is this survival difference.”

What’s next? “In ALL, we now have a number of new modalities to treat high-risk and relapsed disease such as antibodies and CAR-T,” Dr. Nichols said. “We anticipate that 5-year survival can improve utilizing these modalities due to getting more patients into remission, hopefully while reducing chemotherapeutic toxicity.”

Dr. Nichol’s also highlighted the society’s new genomic-led Pediatric Acute Leukemia (PedAL) Master Clinical Trial, which began enrolling children with acute leukemia in the United States and Canada this year, in an effort to transform medicine’s traditional high-level chemotherapy strategy to their care. The project was launched in collaboration with the National Cancer Institute, Children’s Oncology Group, and the European Pediatric Acute Leukemia Foundation.

As part of the screening process, the biology of each child’s cancer will be identified, and families will be encouraged to enroll them in appropriate targeted therapy trials.

“Until we are able to decrease the toxicity of leukemia regimens, we won’t see a dramatic shift in late effects and thus in morbidity and mortality,” Dr. Nichols said. “The trial is an effort to test newer, less toxic regimens to begin to change that cycle.”

The 5-year survival study was funded by Children with Cancer UK, Institut National du Cancer, La Ligue Contre le Cancer, Centers for Disease Control and Prevention, Swiss Re, Swiss Cancer Research foundation, Swiss Cancer League, Rossy Family Foundation, National Cancer Institute, and the American Cancer Society. One author reports a grant from Macmillan Cancer Support, consultancy fees from Pfizer, and unsolicited small gifts from Moondance Cancer Initiative for philanthropic work. The other authors report no disclosures.

The long-term survival study was funded by the National Cancer Institute, the Archer Foundation and LyondellBasell Industries. Dr. Roth reports no disclosures; other authors report various disclosures. Dr. Nichols reports no disclosures.

Two new studies offer insights into leukemia survival rates in the United States. From 2000 to 2014, a drop in mortality among children spurred a rise in 5-year leukemia survival rates among patients aged 0-24. But adolescents and young adults who survive 5 years after diagnosis face an ongoing higher risk of death, recent research revealed, and their long-term survival is lower compared to that of the general population.

“Outcomes are improving. However, additional efforts, support, and resources are needed to further improve short- and long-term survival for acute leukemia survivors. Targeted efforts focused on populations that face greater disparities in their survival are needed to move the needle faster,” Michael Roth, MD, codirector of the Adolescent and Young Adult Oncology Program at the University of Texas M.D. Anderson Cancer Center, said in an interview.

In one study, released in The Lancet Child & Adolescent Health, an international team of researchers tracked survival outcomes from various types of leukemia in 61 nations. The study focused on the years 2000-2014 and followed patients aged 0-24.

“Age-standardized 5-year net survival in children, adolescents, and young adults for all leukemias combined during 2010-14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia,” the researchers wrote. “Throughout 2000-14, survival from all leukemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries.”

The U.S. data came from 41 states that cover 86% of the nation’s population, lead author Naomi Ssenyonga, a research fellow at London School of Hygiene & Tropical Medicine, said in an interview.

The 5-year survival rate for acute lymphoid leukemia (ALL) rose from 80% during 2000-2004 to 86% during 2010-2014. Survival in patients with acute myeloid leukemia (AML) was lower than for other subtypes: 66% in 2010-2014 vs. 57% in 2000-2004.

In regard to all leukemias, “we noted a steady increase in the U.S. of 6 percentage points in 5-year survival, up from 77% for patients diagnosed during 2000-2004 to 83% for those diagnosed during 2010-2014,” Ms. Ssenyonga said. “The gains were largely driven by the improvements seen among children.”

Why haven’t adolescents and young adults gained as much ground in survival?

“They often have unique clinical needs,” Ms. Ssenyonga said. “Over the past few years, adolescents and young adults with leukemia in some parts of the world, including the U.S., have increasingly been treated under pediatric protocols. This has led to higher survival. However, this approach has not been adopted consistently, and survival for adolescents and young adults with leukemia is still generally lower than survival for children.”

Gwen Nichols, MD, chief medical officer of the Leukemia & Lymphoma Society, agreed that pediatric treatment protocols hold promise as treatments for young adults. However, “because we arbitrarily set an age cutoff for being an adult, many of these patients are treated by an adult [nonpediatric] hematologist/oncologist, and some patients in the 20-39 age group do not receive the more intensive treatment regimens given to children,” she said in an interview.

In another study, published in Cancer Epidemiology, Biomarkers, & Prevention, M.D. Anderson Cancer Center’s Dr. Roth and colleagues tracked 1,938 patients with ALL and 2,350 with AML who were diagnosed at ages 15-39 from 1980 to 2009. All lived at least 5 years after diagnosis. In both groups, about 58% were White, and most of the rest were Hispanic. The median age of diagnosis for ALL was 23 (range: 15-39) and 28 years for AML (range: 15-39).

“For ALL, 10-year survival for those diagnosed in the 1980s, 1990s, and 2000s was 83%, 88%, and 88%, respectively,” the researchers reported. “Ten-year survival for AML was 82%, 90%, and 90% for those diagnosed in the 1980s, 1990s, and 2000s, respectively.”

“Early mortality within 10 years of diagnosis was mostly secondary to leukemia progressing or recurring. We believe that later mortality is secondary to the development of late side effects from their cancer treatment,” Dr. Roth said.

He noted that many adolescents and young adults with ALL or AML receive stem-cell transplants. “This treatment approach is effective. However, it is associated with short- and long-term toxicity that impacts patients’ health for many years after treatment.”

Indeed, up to 80% of acute leukemia survivors have significant health complications after therapy, said the Leukemia & Lymphoma Society’s Dr. Nichols, who wasn’t surprised by the findings. According to the society, “even when treatments are effective, more than 70% of childhood cancer survivors have a chronic health condition and 42% have a severe, disabling or life-threatening condition 30 years after diagnosis.”

“It would be interesting to understand the male predominance better,” she added, noting that the study found that male patients had worse long-term survival than females (survival time ratio: 0.61, 95% confidence interval, 0.45-0.82). “While it is tempting to suggest it is due to difference in cardiac disease, I am not aware of data to support why there is this survival difference.”

What’s next? “In ALL, we now have a number of new modalities to treat high-risk and relapsed disease such as antibodies and CAR-T,” Dr. Nichols said. “We anticipate that 5-year survival can improve utilizing these modalities due to getting more patients into remission, hopefully while reducing chemotherapeutic toxicity.”

Dr. Nichol’s also highlighted the society’s new genomic-led Pediatric Acute Leukemia (PedAL) Master Clinical Trial, which began enrolling children with acute leukemia in the United States and Canada this year, in an effort to transform medicine’s traditional high-level chemotherapy strategy to their care. The project was launched in collaboration with the National Cancer Institute, Children’s Oncology Group, and the European Pediatric Acute Leukemia Foundation.

As part of the screening process, the biology of each child’s cancer will be identified, and families will be encouraged to enroll them in appropriate targeted therapy trials.

“Until we are able to decrease the toxicity of leukemia regimens, we won’t see a dramatic shift in late effects and thus in morbidity and mortality,” Dr. Nichols said. “The trial is an effort to test newer, less toxic regimens to begin to change that cycle.”

The 5-year survival study was funded by Children with Cancer UK, Institut National du Cancer, La Ligue Contre le Cancer, Centers for Disease Control and Prevention, Swiss Re, Swiss Cancer Research foundation, Swiss Cancer League, Rossy Family Foundation, National Cancer Institute, and the American Cancer Society. One author reports a grant from Macmillan Cancer Support, consultancy fees from Pfizer, and unsolicited small gifts from Moondance Cancer Initiative for philanthropic work. The other authors report no disclosures.

The long-term survival study was funded by the National Cancer Institute, the Archer Foundation and LyondellBasell Industries. Dr. Roth reports no disclosures; other authors report various disclosures. Dr. Nichols reports no disclosures.

Two new studies offer insights into leukemia survival rates in the United States. From 2000 to 2014, a drop in mortality among children spurred a rise in 5-year leukemia survival rates among patients aged 0-24. But adolescents and young adults who survive 5 years after diagnosis face an ongoing higher risk of death, recent research revealed, and their long-term survival is lower compared to that of the general population.

“Outcomes are improving. However, additional efforts, support, and resources are needed to further improve short- and long-term survival for acute leukemia survivors. Targeted efforts focused on populations that face greater disparities in their survival are needed to move the needle faster,” Michael Roth, MD, codirector of the Adolescent and Young Adult Oncology Program at the University of Texas M.D. Anderson Cancer Center, said in an interview.

In one study, released in The Lancet Child & Adolescent Health, an international team of researchers tracked survival outcomes from various types of leukemia in 61 nations. The study focused on the years 2000-2014 and followed patients aged 0-24.

“Age-standardized 5-year net survival in children, adolescents, and young adults for all leukemias combined during 2010-14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia,” the researchers wrote. “Throughout 2000-14, survival from all leukemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries.”

The U.S. data came from 41 states that cover 86% of the nation’s population, lead author Naomi Ssenyonga, a research fellow at London School of Hygiene & Tropical Medicine, said in an interview.

The 5-year survival rate for acute lymphoid leukemia (ALL) rose from 80% during 2000-2004 to 86% during 2010-2014. Survival in patients with acute myeloid leukemia (AML) was lower than for other subtypes: 66% in 2010-2014 vs. 57% in 2000-2004.

In regard to all leukemias, “we noted a steady increase in the U.S. of 6 percentage points in 5-year survival, up from 77% for patients diagnosed during 2000-2004 to 83% for those diagnosed during 2010-2014,” Ms. Ssenyonga said. “The gains were largely driven by the improvements seen among children.”

Why haven’t adolescents and young adults gained as much ground in survival?

“They often have unique clinical needs,” Ms. Ssenyonga said. “Over the past few years, adolescents and young adults with leukemia in some parts of the world, including the U.S., have increasingly been treated under pediatric protocols. This has led to higher survival. However, this approach has not been adopted consistently, and survival for adolescents and young adults with leukemia is still generally lower than survival for children.”

Gwen Nichols, MD, chief medical officer of the Leukemia & Lymphoma Society, agreed that pediatric treatment protocols hold promise as treatments for young adults. However, “because we arbitrarily set an age cutoff for being an adult, many of these patients are treated by an adult [nonpediatric] hematologist/oncologist, and some patients in the 20-39 age group do not receive the more intensive treatment regimens given to children,” she said in an interview.

In another study, published in Cancer Epidemiology, Biomarkers, & Prevention, M.D. Anderson Cancer Center’s Dr. Roth and colleagues tracked 1,938 patients with ALL and 2,350 with AML who were diagnosed at ages 15-39 from 1980 to 2009. All lived at least 5 years after diagnosis. In both groups, about 58% were White, and most of the rest were Hispanic. The median age of diagnosis for ALL was 23 (range: 15-39) and 28 years for AML (range: 15-39).

“For ALL, 10-year survival for those diagnosed in the 1980s, 1990s, and 2000s was 83%, 88%, and 88%, respectively,” the researchers reported. “Ten-year survival for AML was 82%, 90%, and 90% for those diagnosed in the 1980s, 1990s, and 2000s, respectively.”

“Early mortality within 10 years of diagnosis was mostly secondary to leukemia progressing or recurring. We believe that later mortality is secondary to the development of late side effects from their cancer treatment,” Dr. Roth said.

He noted that many adolescents and young adults with ALL or AML receive stem-cell transplants. “This treatment approach is effective. However, it is associated with short- and long-term toxicity that impacts patients’ health for many years after treatment.”

Indeed, up to 80% of acute leukemia survivors have significant health complications after therapy, said the Leukemia & Lymphoma Society’s Dr. Nichols, who wasn’t surprised by the findings. According to the society, “even when treatments are effective, more than 70% of childhood cancer survivors have a chronic health condition and 42% have a severe, disabling or life-threatening condition 30 years after diagnosis.”

“It would be interesting to understand the male predominance better,” she added, noting that the study found that male patients had worse long-term survival than females (survival time ratio: 0.61, 95% confidence interval, 0.45-0.82). “While it is tempting to suggest it is due to difference in cardiac disease, I am not aware of data to support why there is this survival difference.”

What’s next? “In ALL, we now have a number of new modalities to treat high-risk and relapsed disease such as antibodies and CAR-T,” Dr. Nichols said. “We anticipate that 5-year survival can improve utilizing these modalities due to getting more patients into remission, hopefully while reducing chemotherapeutic toxicity.”

Dr. Nichol’s also highlighted the society’s new genomic-led Pediatric Acute Leukemia (PedAL) Master Clinical Trial, which began enrolling children with acute leukemia in the United States and Canada this year, in an effort to transform medicine’s traditional high-level chemotherapy strategy to their care. The project was launched in collaboration with the National Cancer Institute, Children’s Oncology Group, and the European Pediatric Acute Leukemia Foundation.

As part of the screening process, the biology of each child’s cancer will be identified, and families will be encouraged to enroll them in appropriate targeted therapy trials.

“Until we are able to decrease the toxicity of leukemia regimens, we won’t see a dramatic shift in late effects and thus in morbidity and mortality,” Dr. Nichols said. “The trial is an effort to test newer, less toxic regimens to begin to change that cycle.”

The 5-year survival study was funded by Children with Cancer UK, Institut National du Cancer, La Ligue Contre le Cancer, Centers for Disease Control and Prevention, Swiss Re, Swiss Cancer Research foundation, Swiss Cancer League, Rossy Family Foundation, National Cancer Institute, and the American Cancer Society. One author reports a grant from Macmillan Cancer Support, consultancy fees from Pfizer, and unsolicited small gifts from Moondance Cancer Initiative for philanthropic work. The other authors report no disclosures.

The long-term survival study was funded by the National Cancer Institute, the Archer Foundation and LyondellBasell Industries. Dr. Roth reports no disclosures; other authors report various disclosures. Dr. Nichols reports no disclosures.

The American Academy of Dermatology and the International League of Dermatological Societies (ILDS) have created a new registry that now accepts reports from health care providers worldwide about monkeypox cases and monkeypox vaccine reactions.

Patient data such as names and dates of birth will not be collected.

“As with our joint COVID-19 registry, we will be doing real-time data analysis during the outbreak,” dermatologist Esther Freeman, MD, PhD, director of MGH Global Health Dermatology at Massachusetts General Hospital, Boston, and a member of the AAD’s monkeypox task force, said in an interview. “We will to try to feed information back to our front line in terms of clinical characteristics of cases, morphology, and any unexpected findings.”

NIAID

According to Dr. Freeman, the principal investigator for the COVID-19 registry, this registry has allowed the quick gathering of information about dermatologic findings of COVID-19 from over 53 countries. “We have published over 15 papers, and we share data with outside investigators wishing to do their own analysis of registry-related data,” she said. “Our most-cited paper on COVID vaccine skin reactions has been cited almost 500 times since 2021. It has been used to educate the public on vaccine side effects and to combat vaccine hesitancy.”

The monkeypox registry “doesn’t belong to any one group or person,” Dr. Freeman said. “The idea with rapid data analysis is to be able to give back to the dermatologic community what is hard for us to see with any single case: Patterns and new findings that can be helpful to share with dermatologists and other physicians worldwide, all working together to stop an outbreak.”

The American Academy of Dermatology and the International League of Dermatological Societies (ILDS) have created a new registry that now accepts reports from health care providers worldwide about monkeypox cases and monkeypox vaccine reactions.

Patient data such as names and dates of birth will not be collected.

“As with our joint COVID-19 registry, we will be doing real-time data analysis during the outbreak,” dermatologist Esther Freeman, MD, PhD, director of MGH Global Health Dermatology at Massachusetts General Hospital, Boston, and a member of the AAD’s monkeypox task force, said in an interview. “We will to try to feed information back to our front line in terms of clinical characteristics of cases, morphology, and any unexpected findings.”

NIAID

According to Dr. Freeman, the principal investigator for the COVID-19 registry, this registry has allowed the quick gathering of information about dermatologic findings of COVID-19 from over 53 countries. “We have published over 15 papers, and we share data with outside investigators wishing to do their own analysis of registry-related data,” she said. “Our most-cited paper on COVID vaccine skin reactions has been cited almost 500 times since 2021. It has been used to educate the public on vaccine side effects and to combat vaccine hesitancy.”

The monkeypox registry “doesn’t belong to any one group or person,” Dr. Freeman said. “The idea with rapid data analysis is to be able to give back to the dermatologic community what is hard for us to see with any single case: Patterns and new findings that can be helpful to share with dermatologists and other physicians worldwide, all working together to stop an outbreak.”

The American Academy of Dermatology and the International League of Dermatological Societies (ILDS) have created a new registry that now accepts reports from health care providers worldwide about monkeypox cases and monkeypox vaccine reactions.

Patient data such as names and dates of birth will not be collected.

“As with our joint COVID-19 registry, we will be doing real-time data analysis during the outbreak,” dermatologist Esther Freeman, MD, PhD, director of MGH Global Health Dermatology at Massachusetts General Hospital, Boston, and a member of the AAD’s monkeypox task force, said in an interview. “We will to try to feed information back to our front line in terms of clinical characteristics of cases, morphology, and any unexpected findings.”

NIAID

According to Dr. Freeman, the principal investigator for the COVID-19 registry, this registry has allowed the quick gathering of information about dermatologic findings of COVID-19 from over 53 countries. “We have published over 15 papers, and we share data with outside investigators wishing to do their own analysis of registry-related data,” she said. “Our most-cited paper on COVID vaccine skin reactions has been cited almost 500 times since 2021. It has been used to educate the public on vaccine side effects and to combat vaccine hesitancy.”

The monkeypox registry “doesn’t belong to any one group or person,” Dr. Freeman said. “The idea with rapid data analysis is to be able to give back to the dermatologic community what is hard for us to see with any single case: Patterns and new findings that can be helpful to share with dermatologists and other physicians worldwide, all working together to stop an outbreak.”

Dermatologists are urging colleagues to be on the lookout for monkeypox and cautioning them to not miss cases that might appear to be something else.

Diagnosing cases “can be hard and folks should keep a very open mind and consider monkeypox virus,” said Misha Rosenbach, MD, a University of Pennsylvania dermatologist and member of the American Academy of Dermatology’s ad hoc task force to develop monkeypox content.
 

Although it’s named after a primate, it turns out that monkeypox is quite the copycat. As dermatologists have learned, its lesions can look like those caused by a long list of other diseases including herpes, varicella, and syphilis. In small numbers, they can even appear to be insect bites.

To make things more complicated, a patient can have one or two lesions – or dozens. They often cluster in the anogenital area, likely reflecting transmission via sexual intercourse, unlike previous outbreaks in which lesions appeared all over the body. “We have to let go of some of our conceptions about what monkeypox might look like,” said dermatologist Esther Freeman, MD, PhD, associate professor of dermatology, Harvard University, Boston, and a member of the AAD task force.

Still, the rapid rate of growth of the outbreak – up from 3,487 in the United States on July 25 to 12,689 as of Aug.16 – suggests that more dermatologists will see cases, and consultations may become more common too.
 

Know your lesions

Lesions are the telltale signs of symptomatic monkeypox. According to a recent New England Journal of Medicine study of 528 monkeypox cases from 16 nations, diagnosed between April 27 and June 24, 2022, 95% had skin lesions (58% were vesiculopustular), most commonly in the anogenital area (73%), and on the trunk/arms/or legs (55%) and face (25%), and the palms/soles (10%).

However, “the current monkeypox outbreak often presents differently from the multiple classic vesiculopustules on the skin we see in textbooks,” Dr. Yeung said. “Sometimes people can present with throat pain or rectal pain, with isolated pharyngitis or proctitis. Sometimes there are so few lesions on the skin that it can be easily confused with a bug bite, folliculitis, herpes, dyshidrotic eczema, or other skin problems. This is where dermatologists will get consulted to clarify the diagnosis while the monkeypox PCR test is pending.”

Dr. Rosenbach, who has provided consultation services to other physicians about cases, said the lesions often appear to be vesicles or pustules, “but if you go to ‘pop’ it – e.g., for testing – it’s firm and without fluid. This is likely due to pox virus inclusion, similar to other diseases such as molluscum,” caused by another pox virus, he said. Molluscum lesions are “characteristically umbilicated, with a dimple in the center, and monkeypox lesions seem to be showing a roughly similar morphology with many bowl- or caldera-shaped lesions that are donut-like in appearance,” he added.

Over time, Dr. Rosenbach said, “lesions tend to evolve slowly from smaller flesh-colored or vaguely white firm papules to broader more umbilicated/donut-shaped lesions which may erode, ulcerate, develop a crust or scab, and then heal. The amount of scarring is not yet clear, but we anticipate it to be significant, especially in patients with more widespread or severe disease.”

Jon Peebles, MD, a dermatologist at Kaiser Permanente in Largo, Md., who has treated a few in-person monkeypox cases, said the lesions can be “exquisitely painful,” although he’s also seen patients with asymptomatic lesions. “Lesions are showing a predilection for the anogenital skin, though they can occur anywhere and not uncommonly involve the oral mucosa,” said Dr. Peebles, also a member of the AAD monkeypox task force.

Testing is crucial to rule monkeypox in – or out

While monkeypox lesions can be confused for other diseases, Dr. Rosenbach said that a diagnosis can be confirmed through various tests. Varicella zoster virus (VZV) and herpes simplex virus (HSV) have distinct findings on Tzanck smears (nuclear molding, multinucleated cells), and have widely available fairly rapid tests (PCR, or in some places, DFA). “Staph and bacterial folliculitis can usually be cultured quickly,” he said. “If you have someone with no risk factors/exposure, and you test for VZV, HSV, folliculitis, and it’s negative – you should know within 24 hours in most places – then you can broaden your differential diagnosis and consider alternate explanations, including monkeypox.”

Quest Diagnostics and Labcorp, two of the largest commercial labs in the United States, are now offering monkeypox tests. Labcorp says its test has a 2- to 3-day turnaround time.

As for treatment, some physicians are prescribing off-label use of tecovirimat (also known as TPOXX or ST-246), a smallpox antiviral treatment. The CDC offers guidelines about its use. “It seems to work very fast, with patients improving in 24-72 hours,” Dr. Rosenbach said. However, “it is still very challenging to give and get. There’s a cumbersome system to prescribe it, and it needs to be shipped from the national stockpile. Dermatologists should be working with their state health department, infection control, and infectious disease doctors.”

It’s likely that dermatologists are not comfortable with the process to access the drug, he said, “but if we do not act quickly to control the current outbreak, we will all – unfortunately – need to learn to be comfortable prescribing it.”

In regard to pain control, an over-the-counter painkiller approach may be appropriate depending on comorbidities, Dr. Rosenbach said. “Some patients with very severe disease, such as perianal involvement and proctitis, have such severe pain they need to be hospitalized. This is less common.”

Recommendations pending on scarring prevention

There’s limited high-quality evidence about the prevention of scarring in diseases like monkeypox, Dr. Rosenbach noted. “Any recommendations are usually based on very small, limited, uncontrolled studies. In the case of monkeypox, truly we are off the edge of the map.”

He advises cleaning lesions with gentle soap and water – keeping in mind that contaminated towels may spread disease – and potentially using a topical ointment-based dressing such as a Vaseline/nonstick dressing or Vaseline-impregnated gauze. If there’s concern about superinfection, as can occur with staph infections, topical antibiotics such as mupirocin 2% ointment may be appropriate, he said.

“Some folks like to try silica gel sheets to prevent scarring,” Dr. Rosenbach said. “There’s not a lot of evidence to support that, but they’re unlikely to be harmful. I would personally consider them, but it really depends on the extent of disease, anatomic sites involved, and access to care.”

Emory University’s Dr. Yeung also suggested using silicone gel or sheets to optimize the scar appearance once the lesions have crusted over. “People have used lasers, microneedling, etc., to improve smallpox scar appearance,” he added, “and I’m sure dermatologists will be the ones to study what works best for treating monkeypox scars.”

As for the big picture, Dr. Yeung said that dermatologists are critical in the fight to control monkeypox: “We can help our colleagues and patients manage symptoms and wound care, advocate for vaccination and treatment, treat long-term scarring sequelae, and destigmatize LGBTQ health care.”

The dermatologists interviewed for this article report no disclosures.

Dermatologists are urging colleagues to be on the lookout for monkeypox and cautioning them to not miss cases that might appear to be something else.

Diagnosing cases “can be hard and folks should keep a very open mind and consider monkeypox virus,” said Misha Rosenbach, MD, a University of Pennsylvania dermatologist and member of the American Academy of Dermatology’s ad hoc task force to develop monkeypox content.
 

Although it’s named after a primate, it turns out that monkeypox is quite the copycat. As dermatologists have learned, its lesions can look like those caused by a long list of other diseases including herpes, varicella, and syphilis. In small numbers, they can even appear to be insect bites.

To make things more complicated, a patient can have one or two lesions – or dozens. They often cluster in the anogenital area, likely reflecting transmission via sexual intercourse, unlike previous outbreaks in which lesions appeared all over the body. “We have to let go of some of our conceptions about what monkeypox might look like,” said dermatologist Esther Freeman, MD, PhD, associate professor of dermatology, Harvard University, Boston, and a member of the AAD task force.

Still, the rapid rate of growth of the outbreak – up from 3,487 in the United States on July 25 to 12,689 as of Aug.16 – suggests that more dermatologists will see cases, and consultations may become more common too.
 

Know your lesions

Lesions are the telltale signs of symptomatic monkeypox. According to a recent New England Journal of Medicine study of 528 monkeypox cases from 16 nations, diagnosed between April 27 and June 24, 2022, 95% had skin lesions (58% were vesiculopustular), most commonly in the anogenital area (73%), and on the trunk/arms/or legs (55%) and face (25%), and the palms/soles (10%).

However, “the current monkeypox outbreak often presents differently from the multiple classic vesiculopustules on the skin we see in textbooks,” Dr. Yeung said. “Sometimes people can present with throat pain or rectal pain, with isolated pharyngitis or proctitis. Sometimes there are so few lesions on the skin that it can be easily confused with a bug bite, folliculitis, herpes, dyshidrotic eczema, or other skin problems. This is where dermatologists will get consulted to clarify the diagnosis while the monkeypox PCR test is pending.”

Dr. Rosenbach, who has provided consultation services to other physicians about cases, said the lesions often appear to be vesicles or pustules, “but if you go to ‘pop’ it – e.g., for testing – it’s firm and without fluid. This is likely due to pox virus inclusion, similar to other diseases such as molluscum,” caused by another pox virus, he said. Molluscum lesions are “characteristically umbilicated, with a dimple in the center, and monkeypox lesions seem to be showing a roughly similar morphology with many bowl- or caldera-shaped lesions that are donut-like in appearance,” he added.

Over time, Dr. Rosenbach said, “lesions tend to evolve slowly from smaller flesh-colored or vaguely white firm papules to broader more umbilicated/donut-shaped lesions which may erode, ulcerate, develop a crust or scab, and then heal. The amount of scarring is not yet clear, but we anticipate it to be significant, especially in patients with more widespread or severe disease.”

Jon Peebles, MD, a dermatologist at Kaiser Permanente in Largo, Md., who has treated a few in-person monkeypox cases, said the lesions can be “exquisitely painful,” although he’s also seen patients with asymptomatic lesions. “Lesions are showing a predilection for the anogenital skin, though they can occur anywhere and not uncommonly involve the oral mucosa,” said Dr. Peebles, also a member of the AAD monkeypox task force.

Testing is crucial to rule monkeypox in – or out

While monkeypox lesions can be confused for other diseases, Dr. Rosenbach said that a diagnosis can be confirmed through various tests. Varicella zoster virus (VZV) and herpes simplex virus (HSV) have distinct findings on Tzanck smears (nuclear molding, multinucleated cells), and have widely available fairly rapid tests (PCR, or in some places, DFA). “Staph and bacterial folliculitis can usually be cultured quickly,” he said. “If you have someone with no risk factors/exposure, and you test for VZV, HSV, folliculitis, and it’s negative – you should know within 24 hours in most places – then you can broaden your differential diagnosis and consider alternate explanations, including monkeypox.”

Quest Diagnostics and Labcorp, two of the largest commercial labs in the United States, are now offering monkeypox tests. Labcorp says its test has a 2- to 3-day turnaround time.

As for treatment, some physicians are prescribing off-label use of tecovirimat (also known as TPOXX or ST-246), a smallpox antiviral treatment. The CDC offers guidelines about its use. “It seems to work very fast, with patients improving in 24-72 hours,” Dr. Rosenbach said. However, “it is still very challenging to give and get. There’s a cumbersome system to prescribe it, and it needs to be shipped from the national stockpile. Dermatologists should be working with their state health department, infection control, and infectious disease doctors.”

It’s likely that dermatologists are not comfortable with the process to access the drug, he said, “but if we do not act quickly to control the current outbreak, we will all – unfortunately – need to learn to be comfortable prescribing it.”

In regard to pain control, an over-the-counter painkiller approach may be appropriate depending on comorbidities, Dr. Rosenbach said. “Some patients with very severe disease, such as perianal involvement and proctitis, have such severe pain they need to be hospitalized. This is less common.”

Recommendations pending on scarring prevention

There’s limited high-quality evidence about the prevention of scarring in diseases like monkeypox, Dr. Rosenbach noted. “Any recommendations are usually based on very small, limited, uncontrolled studies. In the case of monkeypox, truly we are off the edge of the map.”

He advises cleaning lesions with gentle soap and water – keeping in mind that contaminated towels may spread disease – and potentially using a topical ointment-based dressing such as a Vaseline/nonstick dressing or Vaseline-impregnated gauze. If there’s concern about superinfection, as can occur with staph infections, topical antibiotics such as mupirocin 2% ointment may be appropriate, he said.

“Some folks like to try silica gel sheets to prevent scarring,” Dr. Rosenbach said. “There’s not a lot of evidence to support that, but they’re unlikely to be harmful. I would personally consider them, but it really depends on the extent of disease, anatomic sites involved, and access to care.”

Emory University’s Dr. Yeung also suggested using silicone gel or sheets to optimize the scar appearance once the lesions have crusted over. “People have used lasers, microneedling, etc., to improve smallpox scar appearance,” he added, “and I’m sure dermatologists will be the ones to study what works best for treating monkeypox scars.”

As for the big picture, Dr. Yeung said that dermatologists are critical in the fight to control monkeypox: “We can help our colleagues and patients manage symptoms and wound care, advocate for vaccination and treatment, treat long-term scarring sequelae, and destigmatize LGBTQ health care.”

The dermatologists interviewed for this article report no disclosures.

Dermatologists are urging colleagues to be on the lookout for monkeypox and cautioning them to not miss cases that might appear to be something else.

Diagnosing cases “can be hard and folks should keep a very open mind and consider monkeypox virus,” said Misha Rosenbach, MD, a University of Pennsylvania dermatologist and member of the American Academy of Dermatology’s ad hoc task force to develop monkeypox content.
 

Although it’s named after a primate, it turns out that monkeypox is quite the copycat. As dermatologists have learned, its lesions can look like those caused by a long list of other diseases including herpes, varicella, and syphilis. In small numbers, they can even appear to be insect bites.

To make things more complicated, a patient can have one or two lesions – or dozens. They often cluster in the anogenital area, likely reflecting transmission via sexual intercourse, unlike previous outbreaks in which lesions appeared all over the body. “We have to let go of some of our conceptions about what monkeypox might look like,” said dermatologist Esther Freeman, MD, PhD, associate professor of dermatology, Harvard University, Boston, and a member of the AAD task force.

Still, the rapid rate of growth of the outbreak – up from 3,487 in the United States on July 25 to 12,689 as of Aug.16 – suggests that more dermatologists will see cases, and consultations may become more common too.
 

Know your lesions

Lesions are the telltale signs of symptomatic monkeypox. According to a recent New England Journal of Medicine study of 528 monkeypox cases from 16 nations, diagnosed between April 27 and June 24, 2022, 95% had skin lesions (58% were vesiculopustular), most commonly in the anogenital area (73%), and on the trunk/arms/or legs (55%) and face (25%), and the palms/soles (10%).

However, “the current monkeypox outbreak often presents differently from the multiple classic vesiculopustules on the skin we see in textbooks,” Dr. Yeung said. “Sometimes people can present with throat pain or rectal pain, with isolated pharyngitis or proctitis. Sometimes there are so few lesions on the skin that it can be easily confused with a bug bite, folliculitis, herpes, dyshidrotic eczema, or other skin problems. This is where dermatologists will get consulted to clarify the diagnosis while the monkeypox PCR test is pending.”

Dr. Rosenbach, who has provided consultation services to other physicians about cases, said the lesions often appear to be vesicles or pustules, “but if you go to ‘pop’ it – e.g., for testing – it’s firm and without fluid. This is likely due to pox virus inclusion, similar to other diseases such as molluscum,” caused by another pox virus, he said. Molluscum lesions are “characteristically umbilicated, with a dimple in the center, and monkeypox lesions seem to be showing a roughly similar morphology with many bowl- or caldera-shaped lesions that are donut-like in appearance,” he added.

Over time, Dr. Rosenbach said, “lesions tend to evolve slowly from smaller flesh-colored or vaguely white firm papules to broader more umbilicated/donut-shaped lesions which may erode, ulcerate, develop a crust or scab, and then heal. The amount of scarring is not yet clear, but we anticipate it to be significant, especially in patients with more widespread or severe disease.”

Jon Peebles, MD, a dermatologist at Kaiser Permanente in Largo, Md., who has treated a few in-person monkeypox cases, said the lesions can be “exquisitely painful,” although he’s also seen patients with asymptomatic lesions. “Lesions are showing a predilection for the anogenital skin, though they can occur anywhere and not uncommonly involve the oral mucosa,” said Dr. Peebles, also a member of the AAD monkeypox task force.

Testing is crucial to rule monkeypox in – or out

While monkeypox lesions can be confused for other diseases, Dr. Rosenbach said that a diagnosis can be confirmed through various tests. Varicella zoster virus (VZV) and herpes simplex virus (HSV) have distinct findings on Tzanck smears (nuclear molding, multinucleated cells), and have widely available fairly rapid tests (PCR, or in some places, DFA). “Staph and bacterial folliculitis can usually be cultured quickly,” he said. “If you have someone with no risk factors/exposure, and you test for VZV, HSV, folliculitis, and it’s negative – you should know within 24 hours in most places – then you can broaden your differential diagnosis and consider alternate explanations, including monkeypox.”

Quest Diagnostics and Labcorp, two of the largest commercial labs in the United States, are now offering monkeypox tests. Labcorp says its test has a 2- to 3-day turnaround time.

As for treatment, some physicians are prescribing off-label use of tecovirimat (also known as TPOXX or ST-246), a smallpox antiviral treatment. The CDC offers guidelines about its use. “It seems to work very fast, with patients improving in 24-72 hours,” Dr. Rosenbach said. However, “it is still very challenging to give and get. There’s a cumbersome system to prescribe it, and it needs to be shipped from the national stockpile. Dermatologists should be working with their state health department, infection control, and infectious disease doctors.”

It’s likely that dermatologists are not comfortable with the process to access the drug, he said, “but if we do not act quickly to control the current outbreak, we will all – unfortunately – need to learn to be comfortable prescribing it.”

In regard to pain control, an over-the-counter painkiller approach may be appropriate depending on comorbidities, Dr. Rosenbach said. “Some patients with very severe disease, such as perianal involvement and proctitis, have such severe pain they need to be hospitalized. This is less common.”

Recommendations pending on scarring prevention

There’s limited high-quality evidence about the prevention of scarring in diseases like monkeypox, Dr. Rosenbach noted. “Any recommendations are usually based on very small, limited, uncontrolled studies. In the case of monkeypox, truly we are off the edge of the map.”

He advises cleaning lesions with gentle soap and water – keeping in mind that contaminated towels may spread disease – and potentially using a topical ointment-based dressing such as a Vaseline/nonstick dressing or Vaseline-impregnated gauze. If there’s concern about superinfection, as can occur with staph infections, topical antibiotics such as mupirocin 2% ointment may be appropriate, he said.

“Some folks like to try silica gel sheets to prevent scarring,” Dr. Rosenbach said. “There’s not a lot of evidence to support that, but they’re unlikely to be harmful. I would personally consider them, but it really depends on the extent of disease, anatomic sites involved, and access to care.”

Emory University’s Dr. Yeung also suggested using silicone gel or sheets to optimize the scar appearance once the lesions have crusted over. “People have used lasers, microneedling, etc., to improve smallpox scar appearance,” he added, “and I’m sure dermatologists will be the ones to study what works best for treating monkeypox scars.”

As for the big picture, Dr. Yeung said that dermatologists are critical in the fight to control monkeypox: “We can help our colleagues and patients manage symptoms and wound care, advocate for vaccination and treatment, treat long-term scarring sequelae, and destigmatize LGBTQ health care.”

The dermatologists interviewed for this article report no disclosures.

The second-generation selective Bruton tyrosine kinase inhibitor (BTKi) zanubrutinib outperformed the standard treatment bendamustine-rituximab in untreated chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), a new industry-funded phase-3 trial found.

At a median follow-up of 26.2 months, progression to worsening disease or death was much lower in patients with these conditions who took zanubrutinib (Brukinsa), compared with those who took bendamustine-rituximab (hazard ratio. 0.42; 95% confidence interval, 0.28-0.63; P < .00011). The study was published in The Lancet Oncology.

Researchers already knew that ibrutinib, another BTKi, improves progression-free survival, study coauthor Paolo Ghia, MD, PhD, professor of medical oncology at Vita-Salute San Raffaele University, Milan, said in an interview. “Now we confirmed that the same advantage can be seen” in zanubrutinib.

According to Dr. Ghia, bendamustine-rituximab has long been a standard treatment in blood cancers and is considered well tolerated and inexpensive. But BTKis such as first-in-line ibrutinib have shown better results, he said, “and progressively, we are going to abandon bendamustine-rituximab.”

However, ibrutinib causes significant adverse effects such as bleeding, worsening hypertension and arrhythmia, he noted. As a result, second-generation BTKi such as zanubrutinib have entered the picture. The Food and Drug Administration approved it in 2019 for mantle cell lymphoma, and it has since been approved for Waldenström’s macroglobulinemia and marginal zone lymphoma.

In 2021, an interim analysis in a trial of the drug in patients with previously treated CLL, compared with ibrutinib, found that “zanubrutinib was shown to have a superior response rate, an improved PFS, and a lower rate of atrial fibrillation/flutter.”

The drug’s manufacturer, BeiGene, launched the new open-label, multicenter study, in a bid for FDA approval of the drug as a frontline treatment for CLL and SLL. More than 150 hospitals in 14 countries participated in the trial from 2017 to 2019.

The subjects were all adults and at least 65 years old or with comorbidities; None had the genetic trait del(17)(p13.1); 241 were assigned to take zanubrutinib and 238 to bendamustine-rituximab. Another group consisted of 111 patients with CLL and del(17)(p13·1). According to the study authors, these patients are especially difficult to treat.

The vast majority of patients were White (92%-95% depending on group) and male (61%-71%); 90%-92% had CLL.

At follow-up, there was no difference in overall survival between the main zanubrutinib and bendamustine-rituximab groups; 29 (12%) of the 241 patients in the zanubrutinib group and 57 (24%) of 238 patients in the bendamustine-rituximab group had progressed or died (HR, 0.42; 95% CI, 0.27-0.66; P < .00011). Adverse events leading to discontinuation were more common in the bendamustine-rituximab group (14%) versus zanubrutinib (8%).

In the third group, which only received zanubrutinib, 14% of patients died at median follow-up of 30.5 months; 98% of patients had adverse effects, and 5% discontinued treatment.

The researchers wrote that “zanubrutinib showed superior progression­-free survival versus bendamustine-rituximab in older patients or those with comorbidities with untreated CLL, with a low incidence of cardiac arrhythmia. Similar efficacy was observed in patients with del(17p)­–positive disease.”

The study didn’t examine cost; zanubrutinib is quite expensive.

In an interview, hematologist-oncologist Anthony Mato, MD, of Memorial Sloan Kettering Cancer Center in New York said the new study is important although not surprising, since other medications in the same class have shown similar results. Zanubrutinib is an alternative to ibrutinib, although the latter remains “an excellent drug,” he said.

“The era of chemotherapy being a first choice is over,” he said. “We’ve had several randomized studies that show targeted therapies are better tolerated and have better outcomes. We now need to look through the choices to decide which one of these good options are the best for our patients.”

In an interview, hematologist-oncologist Joanna Rhodes, MD, of Northwell Health in Hempstead, N.Y., highlighted the side effect profile of zanubrutinib, noting that it is low and resembles that of other BTKis, making it “another excellent treatment option.”

“We are seeing that bruising, upper respiratory tract infections, diarrhea, and arthralgias are the most common side effects,” she said. “Bleeding also is a common side effect, which is consistent across the class of BTKis, with 5% of patients developing a major bleed. Also, 3% of patients treated with zanubrutinib developed atrial fibrillation, which is consistent with data from other trials. Treatment discontinuation rates were low (8%).”

The study was funded by BeiGene. The authors reported multiple disclosures. Dr. Mato reported research or consulting relationships with BeiGene, AstraZeneca, and AbbVie. Dr. Rhodes reported multiple research or consulting relationships with Abbvie, BeiGene, Genentech, and others.

The second-generation selective Bruton tyrosine kinase inhibitor (BTKi) zanubrutinib outperformed the standard treatment bendamustine-rituximab in untreated chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), a new industry-funded phase-3 trial found.

At a median follow-up of 26.2 months, progression to worsening disease or death was much lower in patients with these conditions who took zanubrutinib (Brukinsa), compared with those who took bendamustine-rituximab (hazard ratio. 0.42; 95% confidence interval, 0.28-0.63; P < .00011). The study was published in The Lancet Oncology.

Researchers already knew that ibrutinib, another BTKi, improves progression-free survival, study coauthor Paolo Ghia, MD, PhD, professor of medical oncology at Vita-Salute San Raffaele University, Milan, said in an interview. “Now we confirmed that the same advantage can be seen” in zanubrutinib.

According to Dr. Ghia, bendamustine-rituximab has long been a standard treatment in blood cancers and is considered well tolerated and inexpensive. But BTKis such as first-in-line ibrutinib have shown better results, he said, “and progressively, we are going to abandon bendamustine-rituximab.”

However, ibrutinib causes significant adverse effects such as bleeding, worsening hypertension and arrhythmia, he noted. As a result, second-generation BTKi such as zanubrutinib have entered the picture. The Food and Drug Administration approved it in 2019 for mantle cell lymphoma, and it has since been approved for Waldenström’s macroglobulinemia and marginal zone lymphoma.

In 2021, an interim analysis in a trial of the drug in patients with previously treated CLL, compared with ibrutinib, found that “zanubrutinib was shown to have a superior response rate, an improved PFS, and a lower rate of atrial fibrillation/flutter.”

The drug’s manufacturer, BeiGene, launched the new open-label, multicenter study, in a bid for FDA approval of the drug as a frontline treatment for CLL and SLL. More than 150 hospitals in 14 countries participated in the trial from 2017 to 2019.

The subjects were all adults and at least 65 years old or with comorbidities; None had the genetic trait del(17)(p13.1); 241 were assigned to take zanubrutinib and 238 to bendamustine-rituximab. Another group consisted of 111 patients with CLL and del(17)(p13·1). According to the study authors, these patients are especially difficult to treat.

The vast majority of patients were White (92%-95% depending on group) and male (61%-71%); 90%-92% had CLL.

At follow-up, there was no difference in overall survival between the main zanubrutinib and bendamustine-rituximab groups; 29 (12%) of the 241 patients in the zanubrutinib group and 57 (24%) of 238 patients in the bendamustine-rituximab group had progressed or died (HR, 0.42; 95% CI, 0.27-0.66; P < .00011). Adverse events leading to discontinuation were more common in the bendamustine-rituximab group (14%) versus zanubrutinib (8%).

In the third group, which only received zanubrutinib, 14% of patients died at median follow-up of 30.5 months; 98% of patients had adverse effects, and 5% discontinued treatment.

The researchers wrote that “zanubrutinib showed superior progression­-free survival versus bendamustine-rituximab in older patients or those with comorbidities with untreated CLL, with a low incidence of cardiac arrhythmia. Similar efficacy was observed in patients with del(17p)­–positive disease.”

The study didn’t examine cost; zanubrutinib is quite expensive.

In an interview, hematologist-oncologist Anthony Mato, MD, of Memorial Sloan Kettering Cancer Center in New York said the new study is important although not surprising, since other medications in the same class have shown similar results. Zanubrutinib is an alternative to ibrutinib, although the latter remains “an excellent drug,” he said.

“The era of chemotherapy being a first choice is over,” he said. “We’ve had several randomized studies that show targeted therapies are better tolerated and have better outcomes. We now need to look through the choices to decide which one of these good options are the best for our patients.”

In an interview, hematologist-oncologist Joanna Rhodes, MD, of Northwell Health in Hempstead, N.Y., highlighted the side effect profile of zanubrutinib, noting that it is low and resembles that of other BTKis, making it “another excellent treatment option.”

“We are seeing that bruising, upper respiratory tract infections, diarrhea, and arthralgias are the most common side effects,” she said. “Bleeding also is a common side effect, which is consistent across the class of BTKis, with 5% of patients developing a major bleed. Also, 3% of patients treated with zanubrutinib developed atrial fibrillation, which is consistent with data from other trials. Treatment discontinuation rates were low (8%).”

The study was funded by BeiGene. The authors reported multiple disclosures. Dr. Mato reported research or consulting relationships with BeiGene, AstraZeneca, and AbbVie. Dr. Rhodes reported multiple research or consulting relationships with Abbvie, BeiGene, Genentech, and others.

The second-generation selective Bruton tyrosine kinase inhibitor (BTKi) zanubrutinib outperformed the standard treatment bendamustine-rituximab in untreated chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), a new industry-funded phase-3 trial found.

At a median follow-up of 26.2 months, progression to worsening disease or death was much lower in patients with these conditions who took zanubrutinib (Brukinsa), compared with those who took bendamustine-rituximab (hazard ratio. 0.42; 95% confidence interval, 0.28-0.63; P < .00011). The study was published in The Lancet Oncology.

Researchers already knew that ibrutinib, another BTKi, improves progression-free survival, study coauthor Paolo Ghia, MD, PhD, professor of medical oncology at Vita-Salute San Raffaele University, Milan, said in an interview. “Now we confirmed that the same advantage can be seen” in zanubrutinib.

According to Dr. Ghia, bendamustine-rituximab has long been a standard treatment in blood cancers and is considered well tolerated and inexpensive. But BTKis such as first-in-line ibrutinib have shown better results, he said, “and progressively, we are going to abandon bendamustine-rituximab.”

However, ibrutinib causes significant adverse effects such as bleeding, worsening hypertension and arrhythmia, he noted. As a result, second-generation BTKi such as zanubrutinib have entered the picture. The Food and Drug Administration approved it in 2019 for mantle cell lymphoma, and it has since been approved for Waldenström’s macroglobulinemia and marginal zone lymphoma.

In 2021, an interim analysis in a trial of the drug in patients with previously treated CLL, compared with ibrutinib, found that “zanubrutinib was shown to have a superior response rate, an improved PFS, and a lower rate of atrial fibrillation/flutter.”

The drug’s manufacturer, BeiGene, launched the new open-label, multicenter study, in a bid for FDA approval of the drug as a frontline treatment for CLL and SLL. More than 150 hospitals in 14 countries participated in the trial from 2017 to 2019.

The subjects were all adults and at least 65 years old or with comorbidities; None had the genetic trait del(17)(p13.1); 241 were assigned to take zanubrutinib and 238 to bendamustine-rituximab. Another group consisted of 111 patients with CLL and del(17)(p13·1). According to the study authors, these patients are especially difficult to treat.

The vast majority of patients were White (92%-95% depending on group) and male (61%-71%); 90%-92% had CLL.

At follow-up, there was no difference in overall survival between the main zanubrutinib and bendamustine-rituximab groups; 29 (12%) of the 241 patients in the zanubrutinib group and 57 (24%) of 238 patients in the bendamustine-rituximab group had progressed or died (HR, 0.42; 95% CI, 0.27-0.66; P < .00011). Adverse events leading to discontinuation were more common in the bendamustine-rituximab group (14%) versus zanubrutinib (8%).

In the third group, which only received zanubrutinib, 14% of patients died at median follow-up of 30.5 months; 98% of patients had adverse effects, and 5% discontinued treatment.

The researchers wrote that “zanubrutinib showed superior progression­-free survival versus bendamustine-rituximab in older patients or those with comorbidities with untreated CLL, with a low incidence of cardiac arrhythmia. Similar efficacy was observed in patients with del(17p)­–positive disease.”

The study didn’t examine cost; zanubrutinib is quite expensive.

In an interview, hematologist-oncologist Anthony Mato, MD, of Memorial Sloan Kettering Cancer Center in New York said the new study is important although not surprising, since other medications in the same class have shown similar results. Zanubrutinib is an alternative to ibrutinib, although the latter remains “an excellent drug,” he said.

“The era of chemotherapy being a first choice is over,” he said. “We’ve had several randomized studies that show targeted therapies are better tolerated and have better outcomes. We now need to look through the choices to decide which one of these good options are the best for our patients.”

In an interview, hematologist-oncologist Joanna Rhodes, MD, of Northwell Health in Hempstead, N.Y., highlighted the side effect profile of zanubrutinib, noting that it is low and resembles that of other BTKis, making it “another excellent treatment option.”

“We are seeing that bruising, upper respiratory tract infections, diarrhea, and arthralgias are the most common side effects,” she said. “Bleeding also is a common side effect, which is consistent across the class of BTKis, with 5% of patients developing a major bleed. Also, 3% of patients treated with zanubrutinib developed atrial fibrillation, which is consistent with data from other trials. Treatment discontinuation rates were low (8%).”

The study was funded by BeiGene. The authors reported multiple disclosures. Dr. Mato reported research or consulting relationships with BeiGene, AstraZeneca, and AbbVie. Dr. Rhodes reported multiple research or consulting relationships with Abbvie, BeiGene, Genentech, and others.

In advanced renal cell carcinoma, four out of five immuno-oncology drug-based combination treatments are showing impressive results in trials, a new review finds. Based on initial data, all appear to show advantages over the standard first-line treatment with the older targeted-therapy drug sunitinib.

However, the review, published in the International Journal of Urology, cautions that uncertainty remains because of the “absence of long-term prognostic as well as safety data regarding these combination therapies.”

The review, led by Ken-ichi Harada MD, PhD, of Kobe (Japan) University, notes that the introduction of targeted therapies and immuno-oncology drugs over the last 2 decades has revolutionized the treatment of advanced renal cell carcinoma. Multiple combination therapies based on immuno-oncology drugs are now recommended by treatment guidelines.

However, the lack of head-to-head data means that “it is still challenging for physicians to make the best decision on first-line therapy,” the authors wrote.

In the review, the authors recapped the evidence regarding several combination therapies:

• Ipilimumab plus nivolumab, a combination of two monoclonal antibodies, has shown higher overall survival than sunitinib in multiple studies. Treatment-related adverse events are common, however, with one trial reporting that they led 69% of patients to discontinue treatment. Even so, “ipilimumab plus nivolumab therapy continues to demonstrate durable efficacy benefits over sunitinib in advanced renal cell carcinoma patients classified into intermediate or poor risk group after long-term follow-up.”
• Avelumab, a monoclonal antibody, plus the tyrosine kinase inhibitor (TKI) axitinib has not shown better overall survival rates versus sunitinib in a single trial, although there are signs of better progression-free survival. “Accordingly, avelumab plus axitinib is either not or discreetly recommended as a standard first-line therapy for advanced renal cell carcinoma patients by major clinical guidelines.”
• Pembrolizumab, a monoclonal antibody, plus axitinib has shown better progression-free survival and overall survival than sunitinib in a single trial. “Accordingly, pembrolizumab plus axitinib could be expected to have a powerful impact on favorable long-term cancer control with less frequent occurrence of severe adverse events, considering almost equivalent landmark overall survival to ipilimumab plus nivolumab.”
• Nivolumab plus cabozantinib, a TKI, beat sunitinib in a single trial in terms of progression-free survival and overall survival. “Nivolumab plus cabozantinib could be regarded as an efficacious therapeutic option for untreated advanced renal cell carcinoma patients with manageable safety.”
• Pembrolizumab plus lenvatinib, a TKI, showed better overall survival versus sunitinib in a single trial.

“These findings suggest that pembrolizumab plus lenvatinib could provide marked benefits with regard to cancer control in treatment-naive advanced renal cell carcinoma patients, and that caution should be exercised regarding the safety profile, considering the initial introduction of lenvatinib in the field of urological malignancies,” the authors wrote.

When compared against each other, most of these treatments appear to perform similarly, the authors wrote. With the exception of avelumab plus axitinib, all “showed almost similar advantages for the improvement of overall survival compared with sunitinib, judging from hazard ratios, and all five immuno-oncology drug-based combination therapies, particularly pembrolizumab plus lenvatinib, significantly prolonged progression-free survival, compared with sunitinib.”

No study funding was reported. The authors report various disclosures including relationships to Novartis, Pfizer, Ono, Takeda, MSD, Merck, and Bristol-Myers Squibb.

In advanced renal cell carcinoma, four out of five immuno-oncology drug-based combination treatments are showing impressive results in trials, a new review finds. Based on initial data, all appear to show advantages over the standard first-line treatment with the older targeted-therapy drug sunitinib.

However, the review, published in the International Journal of Urology, cautions that uncertainty remains because of the “absence of long-term prognostic as well as safety data regarding these combination therapies.”

The review, led by Ken-ichi Harada MD, PhD, of Kobe (Japan) University, notes that the introduction of targeted therapies and immuno-oncology drugs over the last 2 decades has revolutionized the treatment of advanced renal cell carcinoma. Multiple combination therapies based on immuno-oncology drugs are now recommended by treatment guidelines.

However, the lack of head-to-head data means that “it is still challenging for physicians to make the best decision on first-line therapy,” the authors wrote.

In the review, the authors recapped the evidence regarding several combination therapies:

• Ipilimumab plus nivolumab, a combination of two monoclonal antibodies, has shown higher overall survival than sunitinib in multiple studies. Treatment-related adverse events are common, however, with one trial reporting that they led 69% of patients to discontinue treatment. Even so, “ipilimumab plus nivolumab therapy continues to demonstrate durable efficacy benefits over sunitinib in advanced renal cell carcinoma patients classified into intermediate or poor risk group after long-term follow-up.”
• Avelumab, a monoclonal antibody, plus the tyrosine kinase inhibitor (TKI) axitinib has not shown better overall survival rates versus sunitinib in a single trial, although there are signs of better progression-free survival. “Accordingly, avelumab plus axitinib is either not or discreetly recommended as a standard first-line therapy for advanced renal cell carcinoma patients by major clinical guidelines.”
• Pembrolizumab, a monoclonal antibody, plus axitinib has shown better progression-free survival and overall survival than sunitinib in a single trial. “Accordingly, pembrolizumab plus axitinib could be expected to have a powerful impact on favorable long-term cancer control with less frequent occurrence of severe adverse events, considering almost equivalent landmark overall survival to ipilimumab plus nivolumab.”
• Nivolumab plus cabozantinib, a TKI, beat sunitinib in a single trial in terms of progression-free survival and overall survival. “Nivolumab plus cabozantinib could be regarded as an efficacious therapeutic option for untreated advanced renal cell carcinoma patients with manageable safety.”
• Pembrolizumab plus lenvatinib, a TKI, showed better overall survival versus sunitinib in a single trial.

“These findings suggest that pembrolizumab plus lenvatinib could provide marked benefits with regard to cancer control in treatment-naive advanced renal cell carcinoma patients, and that caution should be exercised regarding the safety profile, considering the initial introduction of lenvatinib in the field of urological malignancies,” the authors wrote.

When compared against each other, most of these treatments appear to perform similarly, the authors wrote. With the exception of avelumab plus axitinib, all “showed almost similar advantages for the improvement of overall survival compared with sunitinib, judging from hazard ratios, and all five immuno-oncology drug-based combination therapies, particularly pembrolizumab plus lenvatinib, significantly prolonged progression-free survival, compared with sunitinib.”

No study funding was reported. The authors report various disclosures including relationships to Novartis, Pfizer, Ono, Takeda, MSD, Merck, and Bristol-Myers Squibb.

In advanced renal cell carcinoma, four out of five immuno-oncology drug-based combination treatments are showing impressive results in trials, a new review finds. Based on initial data, all appear to show advantages over the standard first-line treatment with the older targeted-therapy drug sunitinib.

However, the review, published in the International Journal of Urology, cautions that uncertainty remains because of the “absence of long-term prognostic as well as safety data regarding these combination therapies.”

The review, led by Ken-ichi Harada MD, PhD, of Kobe (Japan) University, notes that the introduction of targeted therapies and immuno-oncology drugs over the last 2 decades has revolutionized the treatment of advanced renal cell carcinoma. Multiple combination therapies based on immuno-oncology drugs are now recommended by treatment guidelines.

However, the lack of head-to-head data means that “it is still challenging for physicians to make the best decision on first-line therapy,” the authors wrote.

In the review, the authors recapped the evidence regarding several combination therapies:

• Ipilimumab plus nivolumab, a combination of two monoclonal antibodies, has shown higher overall survival than sunitinib in multiple studies. Treatment-related adverse events are common, however, with one trial reporting that they led 69% of patients to discontinue treatment. Even so, “ipilimumab plus nivolumab therapy continues to demonstrate durable efficacy benefits over sunitinib in advanced renal cell carcinoma patients classified into intermediate or poor risk group after long-term follow-up.”
• Avelumab, a monoclonal antibody, plus the tyrosine kinase inhibitor (TKI) axitinib has not shown better overall survival rates versus sunitinib in a single trial, although there are signs of better progression-free survival. “Accordingly, avelumab plus axitinib is either not or discreetly recommended as a standard first-line therapy for advanced renal cell carcinoma patients by major clinical guidelines.”
• Pembrolizumab, a monoclonal antibody, plus axitinib has shown better progression-free survival and overall survival than sunitinib in a single trial. “Accordingly, pembrolizumab plus axitinib could be expected to have a powerful impact on favorable long-term cancer control with less frequent occurrence of severe adverse events, considering almost equivalent landmark overall survival to ipilimumab plus nivolumab.”
• Nivolumab plus cabozantinib, a TKI, beat sunitinib in a single trial in terms of progression-free survival and overall survival. “Nivolumab plus cabozantinib could be regarded as an efficacious therapeutic option for untreated advanced renal cell carcinoma patients with manageable safety.”
• Pembrolizumab plus lenvatinib, a TKI, showed better overall survival versus sunitinib in a single trial.

“These findings suggest that pembrolizumab plus lenvatinib could provide marked benefits with regard to cancer control in treatment-naive advanced renal cell carcinoma patients, and that caution should be exercised regarding the safety profile, considering the initial introduction of lenvatinib in the field of urological malignancies,” the authors wrote.

When compared against each other, most of these treatments appear to perform similarly, the authors wrote. With the exception of avelumab plus axitinib, all “showed almost similar advantages for the improvement of overall survival compared with sunitinib, judging from hazard ratios, and all five immuno-oncology drug-based combination therapies, particularly pembrolizumab plus lenvatinib, significantly prolonged progression-free survival, compared with sunitinib.”

No study funding was reported. The authors report various disclosures including relationships to Novartis, Pfizer, Ono, Takeda, MSD, Merck, and Bristol-Myers Squibb.

New research offers more evidence linking targeted therapies for patients with advanced renal cell carcinoma to higher risks for major adverse cardiovascular events.

Patients on targeted therapy were more likely to develop conditions such as heart attacks and stroke than were those who took cytokine therapy (adjusted hazard ratio, 1.80; 95% confidence interval [CI] 1.19-2.74), according to a retrospective Taiwanese study reports.

“These findings may inform the evaluation of cardiovascular risk when considering targeted cancer therapies for patients with advanced renal cell carcinoma in real-world clinical practice,” wrote the authors of the report, which appeared in JACC: CardioOncology.

The study notes that one kind of targeted therapy – tyrosine kinase inhibitors with anti–vascular endothelial growth factor (VEGFR-TKI) have been linked to higher rates of major adverse cardiovascular events (1.38-22.7). There have also been reports linking another kind of targeted therapy, mechanistic target of rapamycin inhibitors (mTOR), to major adverse cardiovascular events.

In the new study, Dong-Yi Chen, MD, of Chang Gung University, Taiwan, and colleagues, tracked patients with renal cell carcinoma who underwent treatment with targeted therapy (sunitinib, sorafenib, pazopanib, everolimus, or temsirolimus, (n = 2,257, 81%) or cytokine therapy (interleukin-2 or interferon gamma, n = 528, 19%) from 2007 to 2018.

The two groups had similar gender, age and socioeconomic levels. Combined, the groups were 74% male, the median age was 63, and 68% had hypertension.

After stabilized inverse probability of treatment weighting, the adjusted incidence rates of major cardiovascular events were 6.65 and 3.36 per 100 person-years in the targeted and cytokine therapy groups, respectively. “The higher cardiovascular risk of the targeted group was driven primarily by the VEGFR TKI–treated patients,” the authors wrote.

Two drugs were linked to statistically significant higher rates of major cardiovascular adverse events compared with the reference drug sunitinib: the VEGFR TKI sorafenib (univariable HR, 1.94, 95% CI, 1.11-3.39), P = .021) and the mTOR temsirolimus (univariable HR, 2.11, 95% CI, 1.24-3.59, P = .006). Sunitinib was by far the most commonly used targeted therapy drug.

Among patients on targeted therapy, several factors were linked to higher rates of major cardiovascular events, such as baseline history of heart failure (HR, 3.88, 95% CI, 2.25-6.71), atrial fibrillation (HR, 3.60, 95% CI, 2.16-5.99), venous thromboembolism (HR, 2.50, 95% CI, 1.27-4.92), ischemic stroke (HR, 1.88, 95% CI, 1.14-3.11), and age at least 65 years (HR, 1.81, 95% CI, 1.27-2.58).

According to the authors, there are several theories about why targeted therapy may boost the risk of major adverse cardiovascular risk. “VEGF signaling inhibitors have been associated with hypertension,” which is a risk factor for cardiac death, they noted. Also, “multi-receptor TKIs, including VEGFR and platelet-derived growth factor receptor inhibitors, could destabilize the coronary microvascular endothelial network and reduce coronary flow reserve, leading to an increased risk for thrombosis and arterial ischemic events, including myocardial infarction and ischemic stroke.”

The study was funded by Chang Gung Memorial Hospital.

New research offers more evidence linking targeted therapies for patients with advanced renal cell carcinoma to higher risks for major adverse cardiovascular events.

Patients on targeted therapy were more likely to develop conditions such as heart attacks and stroke than were those who took cytokine therapy (adjusted hazard ratio, 1.80; 95% confidence interval [CI] 1.19-2.74), according to a retrospective Taiwanese study reports.

“These findings may inform the evaluation of cardiovascular risk when considering targeted cancer therapies for patients with advanced renal cell carcinoma in real-world clinical practice,” wrote the authors of the report, which appeared in JACC: CardioOncology.

The study notes that one kind of targeted therapy – tyrosine kinase inhibitors with anti–vascular endothelial growth factor (VEGFR-TKI) have been linked to higher rates of major adverse cardiovascular events (1.38-22.7). There have also been reports linking another kind of targeted therapy, mechanistic target of rapamycin inhibitors (mTOR), to major adverse cardiovascular events.

In the new study, Dong-Yi Chen, MD, of Chang Gung University, Taiwan, and colleagues, tracked patients with renal cell carcinoma who underwent treatment with targeted therapy (sunitinib, sorafenib, pazopanib, everolimus, or temsirolimus, (n = 2,257, 81%) or cytokine therapy (interleukin-2 or interferon gamma, n = 528, 19%) from 2007 to 2018.

The two groups had similar gender, age and socioeconomic levels. Combined, the groups were 74% male, the median age was 63, and 68% had hypertension.

After stabilized inverse probability of treatment weighting, the adjusted incidence rates of major cardiovascular events were 6.65 and 3.36 per 100 person-years in the targeted and cytokine therapy groups, respectively. “The higher cardiovascular risk of the targeted group was driven primarily by the VEGFR TKI–treated patients,” the authors wrote.

Two drugs were linked to statistically significant higher rates of major cardiovascular adverse events compared with the reference drug sunitinib: the VEGFR TKI sorafenib (univariable HR, 1.94, 95% CI, 1.11-3.39), P = .021) and the mTOR temsirolimus (univariable HR, 2.11, 95% CI, 1.24-3.59, P = .006). Sunitinib was by far the most commonly used targeted therapy drug.

Among patients on targeted therapy, several factors were linked to higher rates of major cardiovascular events, such as baseline history of heart failure (HR, 3.88, 95% CI, 2.25-6.71), atrial fibrillation (HR, 3.60, 95% CI, 2.16-5.99), venous thromboembolism (HR, 2.50, 95% CI, 1.27-4.92), ischemic stroke (HR, 1.88, 95% CI, 1.14-3.11), and age at least 65 years (HR, 1.81, 95% CI, 1.27-2.58).

According to the authors, there are several theories about why targeted therapy may boost the risk of major adverse cardiovascular risk. “VEGF signaling inhibitors have been associated with hypertension,” which is a risk factor for cardiac death, they noted. Also, “multi-receptor TKIs, including VEGFR and platelet-derived growth factor receptor inhibitors, could destabilize the coronary microvascular endothelial network and reduce coronary flow reserve, leading to an increased risk for thrombosis and arterial ischemic events, including myocardial infarction and ischemic stroke.”

The study was funded by Chang Gung Memorial Hospital.

New research offers more evidence linking targeted therapies for patients with advanced renal cell carcinoma to higher risks for major adverse cardiovascular events.

Patients on targeted therapy were more likely to develop conditions such as heart attacks and stroke than were those who took cytokine therapy (adjusted hazard ratio, 1.80; 95% confidence interval [CI] 1.19-2.74), according to a retrospective Taiwanese study reports.

“These findings may inform the evaluation of cardiovascular risk when considering targeted cancer therapies for patients with advanced renal cell carcinoma in real-world clinical practice,” wrote the authors of the report, which appeared in JACC: CardioOncology.

The study notes that one kind of targeted therapy – tyrosine kinase inhibitors with anti–vascular endothelial growth factor (VEGFR-TKI) have been linked to higher rates of major adverse cardiovascular events (1.38-22.7). There have also been reports linking another kind of targeted therapy, mechanistic target of rapamycin inhibitors (mTOR), to major adverse cardiovascular events.

In the new study, Dong-Yi Chen, MD, of Chang Gung University, Taiwan, and colleagues, tracked patients with renal cell carcinoma who underwent treatment with targeted therapy (sunitinib, sorafenib, pazopanib, everolimus, or temsirolimus, (n = 2,257, 81%) or cytokine therapy (interleukin-2 or interferon gamma, n = 528, 19%) from 2007 to 2018.

The two groups had similar gender, age and socioeconomic levels. Combined, the groups were 74% male, the median age was 63, and 68% had hypertension.

After stabilized inverse probability of treatment weighting, the adjusted incidence rates of major cardiovascular events were 6.65 and 3.36 per 100 person-years in the targeted and cytokine therapy groups, respectively. “The higher cardiovascular risk of the targeted group was driven primarily by the VEGFR TKI–treated patients,” the authors wrote.

Two drugs were linked to statistically significant higher rates of major cardiovascular adverse events compared with the reference drug sunitinib: the VEGFR TKI sorafenib (univariable HR, 1.94, 95% CI, 1.11-3.39), P = .021) and the mTOR temsirolimus (univariable HR, 2.11, 95% CI, 1.24-3.59, P = .006). Sunitinib was by far the most commonly used targeted therapy drug.

Among patients on targeted therapy, several factors were linked to higher rates of major cardiovascular events, such as baseline history of heart failure (HR, 3.88, 95% CI, 2.25-6.71), atrial fibrillation (HR, 3.60, 95% CI, 2.16-5.99), venous thromboembolism (HR, 2.50, 95% CI, 1.27-4.92), ischemic stroke (HR, 1.88, 95% CI, 1.14-3.11), and age at least 65 years (HR, 1.81, 95% CI, 1.27-2.58).

According to the authors, there are several theories about why targeted therapy may boost the risk of major adverse cardiovascular risk. “VEGF signaling inhibitors have been associated with hypertension,” which is a risk factor for cardiac death, they noted. Also, “multi-receptor TKIs, including VEGFR and platelet-derived growth factor receptor inhibitors, could destabilize the coronary microvascular endothelial network and reduce coronary flow reserve, leading to an increased risk for thrombosis and arterial ischemic events, including myocardial infarction and ischemic stroke.”

The study was funded by Chang Gung Memorial Hospital.

A new, industry-funded consensus statement from an international team of hematologists, oncologists, and cardio-oncologists urges caution regarding the cardiac risks of Bruton tyrosine kinase inhibitors (BTKis) in treating chronic lymphocytic leukemia (CLL).

The report discourages the use of the drugs in patients with heart failure, and it specifies that ibrutinib should be avoided in cases of ventricular fibrillation. The consensus statement appeared in the journal Blood Advances.

However, a physician who studies the intersection of cardiology and oncology questioned the report's methodology and said that it goes too far in its warnings about the use of BTKis. Also, the report is funded by AstraZeneca, which produces acalabrutinib, a rival BTKi product to ibrutinib.

“BTK inhibitors have revolutionized treatment outcomes and strategies in both the upfront and refractory CLL disease settings. Led by ibrutinib, the drugs are associated with dramatic improvements in long-term survival and disease outcomes for most CLL patients,” report co-author and cardiologist Daniel Addison, MD, co-director of the cardio-oncology program at the Ohio State University, said in an interview. “The main cardiac concerns are abnormal heart rhythms, high blood pressure, and heart weakness. It is not completely clear at this time why these things develop when patients are treated with these important drugs.”

For the new consensus statement, colleagues met virtually and examined peer-reviewed research. “Generally, this statement reflects available knowledge from cancer clinical trials,” Dr. Addison said. “Because of the design of these trials, cardiac analyses were secondary analyses. In terms of clinic use, this should be balanced against a large number of heart-focused retrospective examinations specifically describing the cardiac effects of these drugs. Most of the available heart-focused studies have not been prospective trials. Primary outcome heart-focused trials with BTK inhibitors are needed. This statement acknowledges this.”

The report recommends that all patients under consideration for BTKi therapy undergo electrocardiograms and blood pressure measurement, and it states that echocardiograms are appropriate for patients with heart disease or at high risk. Patients under 70 without risk factors may take ibrutinib, acalabrutinib, or zanubrutinib, while the latter two drugs are “generally preferred” in patients with established heart disease, well-controlled atrial fibrillation (AFib), hypertension, heart failure, or valvular heart disease.

The authors noted: “If the patient has difficult-to-manage AF[ib], recent acute coronary syndromes, or difficult to control heart failure, alternatives to BTKi treatment, including venetoclax, should be considered.”

As for patients with heart failure, the authors wrote that BTKis should be avoided, “but this is a relative contraindication, not an absolute one.” Ibrutinib should definitely be avoided because of the risk of AFib.

Finally, the authors stated that “the use of BTKis, especially ibrutinib, should be avoided in patients with a history of ventricular arrhythmias and cardiac arrest. Ibrutinib has been shown to increase the incidence of ventricular arrhythmias and sudden cardiac death. Although data are not yet available regarding whether second-generation BTKis [acalabrutinib or zanubrutinib] are also associated with these events, a Bcl-2 antagonist is preferred to any BTKi in these patients.”

Darryl P. Leong, MBBS, PhD, MPH, director of the cardio-oncology program at McMaster University, Hamilton, Ont., and Hamilton Health Sciences, said in an interview that the consensus statement has important limitations.

“The data extracted were not standardized. The authors of the original research were not contacted to provide data that might have been informative,” he said. “Finally and perhaps most importantly, I am uncertain that the quality of the data on which recommendations are made was well evaluated or described.”

Specifically, Dr. Leong said the report’s conclusions about heart failure and arrhythmias are not “necessarily well-supported by the evidence.”

He added: “While there is some evidence to suggest that BTKIs may increase heart failure risk, ibrutinib leads to substantial reductions in mortality. It is a large extrapolation to accept that a mostly theoretic risk of heart failure –with modest supporting empiric data – should outweigh proven reductions in death.”

As for the recommendation against the use of ibrutinib in patients with ventricular arrhythmias and cardiac arrest, he said the evidence cited by the report – an analysis of adverse event data prompted by a case report and a retrospective analysis – is limited. “The statement that ibrutinib increases the risk of ventricular arrhythmias and sudden death is more of a hypothesis at present, and the evidence to support this hypothesis is far from conclusive.”

As for the future, report co-author Dr. Addison said that “additional prospective and lab-based studies of these drugs are needed to guide how to best manage their cardiac effects in the future. This will be critical, as the use of these drugs continues to rapidly expand. Currently, we do not know a lot about why these heart issues really happen.”

The study was funded by AstraZeneca. Several authors reported multiple disclosures. Dr. Addison disclosed funding from AstraZeneca. Dr. Leong reported consulting and speaker fees from Janssen, maker of ibrutinib, as well as AstraZeneca.

A new, industry-funded consensus statement from an international team of hematologists, oncologists, and cardio-oncologists urges caution regarding the cardiac risks of Bruton tyrosine kinase inhibitors (BTKis) in treating chronic lymphocytic leukemia (CLL).

The report discourages the use of the drugs in patients with heart failure, and it specifies that ibrutinib should be avoided in cases of ventricular fibrillation. The consensus statement appeared in the journal Blood Advances.

However, a physician who studies the intersection of cardiology and oncology questioned the report's methodology and said that it goes too far in its warnings about the use of BTKis. Also, the report is funded by AstraZeneca, which produces acalabrutinib, a rival BTKi product to ibrutinib.

“BTK inhibitors have revolutionized treatment outcomes and strategies in both the upfront and refractory CLL disease settings. Led by ibrutinib, the drugs are associated with dramatic improvements in long-term survival and disease outcomes for most CLL patients,” report co-author and cardiologist Daniel Addison, MD, co-director of the cardio-oncology program at the Ohio State University, said in an interview. “The main cardiac concerns are abnormal heart rhythms, high blood pressure, and heart weakness. It is not completely clear at this time why these things develop when patients are treated with these important drugs.”

For the new consensus statement, colleagues met virtually and examined peer-reviewed research. “Generally, this statement reflects available knowledge from cancer clinical trials,” Dr. Addison said. “Because of the design of these trials, cardiac analyses were secondary analyses. In terms of clinic use, this should be balanced against a large number of heart-focused retrospective examinations specifically describing the cardiac effects of these drugs. Most of the available heart-focused studies have not been prospective trials. Primary outcome heart-focused trials with BTK inhibitors are needed. This statement acknowledges this.”

The report recommends that all patients under consideration for BTKi therapy undergo electrocardiograms and blood pressure measurement, and it states that echocardiograms are appropriate for patients with heart disease or at high risk. Patients under 70 without risk factors may take ibrutinib, acalabrutinib, or zanubrutinib, while the latter two drugs are “generally preferred” in patients with established heart disease, well-controlled atrial fibrillation (AFib), hypertension, heart failure, or valvular heart disease.

The authors noted: “If the patient has difficult-to-manage AF[ib], recent acute coronary syndromes, or difficult to control heart failure, alternatives to BTKi treatment, including venetoclax, should be considered.”

As for patients with heart failure, the authors wrote that BTKis should be avoided, “but this is a relative contraindication, not an absolute one.” Ibrutinib should definitely be avoided because of the risk of AFib.

Finally, the authors stated that “the use of BTKis, especially ibrutinib, should be avoided in patients with a history of ventricular arrhythmias and cardiac arrest. Ibrutinib has been shown to increase the incidence of ventricular arrhythmias and sudden cardiac death. Although data are not yet available regarding whether second-generation BTKis [acalabrutinib or zanubrutinib] are also associated with these events, a Bcl-2 antagonist is preferred to any BTKi in these patients.”

Darryl P. Leong, MBBS, PhD, MPH, director of the cardio-oncology program at McMaster University, Hamilton, Ont., and Hamilton Health Sciences, said in an interview that the consensus statement has important limitations.

“The data extracted were not standardized. The authors of the original research were not contacted to provide data that might have been informative,” he said. “Finally and perhaps most importantly, I am uncertain that the quality of the data on which recommendations are made was well evaluated or described.”

Specifically, Dr. Leong said the report’s conclusions about heart failure and arrhythmias are not “necessarily well-supported by the evidence.”

He added: “While there is some evidence to suggest that BTKIs may increase heart failure risk, ibrutinib leads to substantial reductions in mortality. It is a large extrapolation to accept that a mostly theoretic risk of heart failure –with modest supporting empiric data – should outweigh proven reductions in death.”

As for the recommendation against the use of ibrutinib in patients with ventricular arrhythmias and cardiac arrest, he said the evidence cited by the report – an analysis of adverse event data prompted by a case report and a retrospective analysis – is limited. “The statement that ibrutinib increases the risk of ventricular arrhythmias and sudden death is more of a hypothesis at present, and the evidence to support this hypothesis is far from conclusive.”

As for the future, report co-author Dr. Addison said that “additional prospective and lab-based studies of these drugs are needed to guide how to best manage their cardiac effects in the future. This will be critical, as the use of these drugs continues to rapidly expand. Currently, we do not know a lot about why these heart issues really happen.”

The study was funded by AstraZeneca. Several authors reported multiple disclosures. Dr. Addison disclosed funding from AstraZeneca. Dr. Leong reported consulting and speaker fees from Janssen, maker of ibrutinib, as well as AstraZeneca.

A new, industry-funded consensus statement from an international team of hematologists, oncologists, and cardio-oncologists urges caution regarding the cardiac risks of Bruton tyrosine kinase inhibitors (BTKis) in treating chronic lymphocytic leukemia (CLL).

The report discourages the use of the drugs in patients with heart failure, and it specifies that ibrutinib should be avoided in cases of ventricular fibrillation. The consensus statement appeared in the journal Blood Advances.

However, a physician who studies the intersection of cardiology and oncology questioned the report's methodology and said that it goes too far in its warnings about the use of BTKis. Also, the report is funded by AstraZeneca, which produces acalabrutinib, a rival BTKi product to ibrutinib.

“BTK inhibitors have revolutionized treatment outcomes and strategies in both the upfront and refractory CLL disease settings. Led by ibrutinib, the drugs are associated with dramatic improvements in long-term survival and disease outcomes for most CLL patients,” report co-author and cardiologist Daniel Addison, MD, co-director of the cardio-oncology program at the Ohio State University, said in an interview. “The main cardiac concerns are abnormal heart rhythms, high blood pressure, and heart weakness. It is not completely clear at this time why these things develop when patients are treated with these important drugs.”

For the new consensus statement, colleagues met virtually and examined peer-reviewed research. “Generally, this statement reflects available knowledge from cancer clinical trials,” Dr. Addison said. “Because of the design of these trials, cardiac analyses were secondary analyses. In terms of clinic use, this should be balanced against a large number of heart-focused retrospective examinations specifically describing the cardiac effects of these drugs. Most of the available heart-focused studies have not been prospective trials. Primary outcome heart-focused trials with BTK inhibitors are needed. This statement acknowledges this.”

The report recommends that all patients under consideration for BTKi therapy undergo electrocardiograms and blood pressure measurement, and it states that echocardiograms are appropriate for patients with heart disease or at high risk. Patients under 70 without risk factors may take ibrutinib, acalabrutinib, or zanubrutinib, while the latter two drugs are “generally preferred” in patients with established heart disease, well-controlled atrial fibrillation (AFib), hypertension, heart failure, or valvular heart disease.

The authors noted: “If the patient has difficult-to-manage AF[ib], recent acute coronary syndromes, or difficult to control heart failure, alternatives to BTKi treatment, including venetoclax, should be considered.”

As for patients with heart failure, the authors wrote that BTKis should be avoided, “but this is a relative contraindication, not an absolute one.” Ibrutinib should definitely be avoided because of the risk of AFib.

Finally, the authors stated that “the use of BTKis, especially ibrutinib, should be avoided in patients with a history of ventricular arrhythmias and cardiac arrest. Ibrutinib has been shown to increase the incidence of ventricular arrhythmias and sudden cardiac death. Although data are not yet available regarding whether second-generation BTKis [acalabrutinib or zanubrutinib] are also associated with these events, a Bcl-2 antagonist is preferred to any BTKi in these patients.”

Darryl P. Leong, MBBS, PhD, MPH, director of the cardio-oncology program at McMaster University, Hamilton, Ont., and Hamilton Health Sciences, said in an interview that the consensus statement has important limitations.

“The data extracted were not standardized. The authors of the original research were not contacted to provide data that might have been informative,” he said. “Finally and perhaps most importantly, I am uncertain that the quality of the data on which recommendations are made was well evaluated or described.”

Specifically, Dr. Leong said the report’s conclusions about heart failure and arrhythmias are not “necessarily well-supported by the evidence.”

He added: “While there is some evidence to suggest that BTKIs may increase heart failure risk, ibrutinib leads to substantial reductions in mortality. It is a large extrapolation to accept that a mostly theoretic risk of heart failure –with modest supporting empiric data – should outweigh proven reductions in death.”

As for the recommendation against the use of ibrutinib in patients with ventricular arrhythmias and cardiac arrest, he said the evidence cited by the report – an analysis of adverse event data prompted by a case report and a retrospective analysis – is limited. “The statement that ibrutinib increases the risk of ventricular arrhythmias and sudden death is more of a hypothesis at present, and the evidence to support this hypothesis is far from conclusive.”

As for the future, report co-author Dr. Addison said that “additional prospective and lab-based studies of these drugs are needed to guide how to best manage their cardiac effects in the future. This will be critical, as the use of these drugs continues to rapidly expand. Currently, we do not know a lot about why these heart issues really happen.”

The study was funded by AstraZeneca. Several authors reported multiple disclosures. Dr. Addison disclosed funding from AstraZeneca. Dr. Leong reported consulting and speaker fees from Janssen, maker of ibrutinib, as well as AstraZeneca.