Randy Dotinga

Treat acne from near birth to adulthood with a growing level of aggressiveness as a child ages, a dermatologist urged colleagues.

No treatment may be necessary for acne in the first few months of life, but the condition can leave scars in children as young as ages 3-6 months, said Andrea L. Zaenglein, MD, professor of dermatology and pediatric dermatology, Penn State University, Hershey, Penn., said in a presentation at MedscapeLive’s virtual Women’s & Pediatric Dermatology Seminar.

Neonatal acne occurs in more than 20% of newborns aged 2 weeks to 3 months. “Typically we don’t need to treat it. But if you do, you could use a topical antifungal like clotrimazole cream twice a day,” but in most babies, “this will just improve over time and resolve without any scarring or sequelae,” she said.

Infantile acne begins about 3-6 months of age typically, or a little bit older, and lasts up to 2 years of age, Dr. Zaenglein said. “You will see comedones in infantile acne, so this is actually a true form of acne. It’s due to increased adrenal production of androgens.”

She added: “The scarring can be permanent. It’s important that you recognize infantile acne and treat it, even though it seems pretty mild.”

For infantile acne, she recommends performing a full-skin exam to rule out hyperandrogenic disorders such as Cushing syndrome, congenital adrenal hyperplasia, premature adrenarche, a gonadal/adrenal tumor and precocious puberty.

Treatments are similar to those in teenagers, she said, “but make sure you use baby-friendly formulations,” with lower concentrations of active ingredients – and avoid tetracyclines and benzoyl peroxide (BPO) washes. BPO can be used in leave-on formulations/creams at lower strengths (2.5%-5%).

One possible combination option is tretinoin 0.025% cream or adapalene 0.1% gel plus BPO 2.5% cream or clindamycin/BPO gel. Another combination is adapalene/BPO 2.5% gel.

Erythromycin can be appropriate at 30-50 mg/kg per day divided in two or three doses a day, but beware of possible gastrointestinal upset. Azithromycin at 5 mg/kg per day is another option.

“Rarely do we have to go to isotretinoin,” Dr. Zaenglein said. “I think in all my years, I’ve only treated one baby with isotretinoin for infantile acne. But severe forms can occur.”

Midchildhood and preadolescent acne conditions occur in children starting at ages 1 up to 10 years, Dr. Zaenglein said. In this population, she also recommends ruling out hyperandrogenism by looking for secondary sexual characteristics with full-body skin exams. “The workup can be broad and includes looking at adrenal androgens and total and free testosterone, as well as looking at growth charts and bone age. Typically, you’ll refer these kids to pediatric endocrinology.”

Keep in mind, she said, that early adrenarche starts at ages 6-7 years in girls and 7-8 years in boys. “That’s when we expect to start seeing that very early acne. You can see it even earlier in patients with elevated BMI, and it’s more common in Hispanic and Black children as well.”

She added that it’s important to remember that early adrenarche is a risk factor for polycystic ovarian syndrome (PCOS). “So ask patients about their family history and look for other signs of PCOS as they move further into adolescence.”

Milder cases of acne in this age group can be treated with “salicylic acid wipes and things that are kind of a rite of passage. But if they have any more severe acne, you’re going to want to treat it more or less like you do adolescent acne.”

MedscapeLive and this news organization are owned by the same parent company. Dr. Zaenglein disclosed receiving consulting fees from Cassiopea, Dermata, and Regeneron and fees for contracted research support from Incyte.

Treat acne from near birth to adulthood with a growing level of aggressiveness as a child ages, a dermatologist urged colleagues.

No treatment may be necessary for acne in the first few months of life, but the condition can leave scars in children as young as ages 3-6 months, said Andrea L. Zaenglein, MD, professor of dermatology and pediatric dermatology, Penn State University, Hershey, Penn., said in a presentation at MedscapeLive’s virtual Women’s & Pediatric Dermatology Seminar.

Neonatal acne occurs in more than 20% of newborns aged 2 weeks to 3 months. “Typically we don’t need to treat it. But if you do, you could use a topical antifungal like clotrimazole cream twice a day,” but in most babies, “this will just improve over time and resolve without any scarring or sequelae,” she said.

Infantile acne begins about 3-6 months of age typically, or a little bit older, and lasts up to 2 years of age, Dr. Zaenglein said. “You will see comedones in infantile acne, so this is actually a true form of acne. It’s due to increased adrenal production of androgens.”

She added: “The scarring can be permanent. It’s important that you recognize infantile acne and treat it, even though it seems pretty mild.”

For infantile acne, she recommends performing a full-skin exam to rule out hyperandrogenic disorders such as Cushing syndrome, congenital adrenal hyperplasia, premature adrenarche, a gonadal/adrenal tumor and precocious puberty.

Treatments are similar to those in teenagers, she said, “but make sure you use baby-friendly formulations,” with lower concentrations of active ingredients – and avoid tetracyclines and benzoyl peroxide (BPO) washes. BPO can be used in leave-on formulations/creams at lower strengths (2.5%-5%).

One possible combination option is tretinoin 0.025% cream or adapalene 0.1% gel plus BPO 2.5% cream or clindamycin/BPO gel. Another combination is adapalene/BPO 2.5% gel.

Erythromycin can be appropriate at 30-50 mg/kg per day divided in two or three doses a day, but beware of possible gastrointestinal upset. Azithromycin at 5 mg/kg per day is another option.

“Rarely do we have to go to isotretinoin,” Dr. Zaenglein said. “I think in all my years, I’ve only treated one baby with isotretinoin for infantile acne. But severe forms can occur.”

Midchildhood and preadolescent acne conditions occur in children starting at ages 1 up to 10 years, Dr. Zaenglein said. In this population, she also recommends ruling out hyperandrogenism by looking for secondary sexual characteristics with full-body skin exams. “The workup can be broad and includes looking at adrenal androgens and total and free testosterone, as well as looking at growth charts and bone age. Typically, you’ll refer these kids to pediatric endocrinology.”

Keep in mind, she said, that early adrenarche starts at ages 6-7 years in girls and 7-8 years in boys. “That’s when we expect to start seeing that very early acne. You can see it even earlier in patients with elevated BMI, and it’s more common in Hispanic and Black children as well.”

She added that it’s important to remember that early adrenarche is a risk factor for polycystic ovarian syndrome (PCOS). “So ask patients about their family history and look for other signs of PCOS as they move further into adolescence.”

Milder cases of acne in this age group can be treated with “salicylic acid wipes and things that are kind of a rite of passage. But if they have any more severe acne, you’re going to want to treat it more or less like you do adolescent acne.”

MedscapeLive and this news organization are owned by the same parent company. Dr. Zaenglein disclosed receiving consulting fees from Cassiopea, Dermata, and Regeneron and fees for contracted research support from Incyte.

Treat acne from near birth to adulthood with a growing level of aggressiveness as a child ages, a dermatologist urged colleagues.

No treatment may be necessary for acne in the first few months of life, but the condition can leave scars in children as young as ages 3-6 months, said Andrea L. Zaenglein, MD, professor of dermatology and pediatric dermatology, Penn State University, Hershey, Penn., said in a presentation at MedscapeLive’s virtual Women’s & Pediatric Dermatology Seminar.

Neonatal acne occurs in more than 20% of newborns aged 2 weeks to 3 months. “Typically we don’t need to treat it. But if you do, you could use a topical antifungal like clotrimazole cream twice a day,” but in most babies, “this will just improve over time and resolve without any scarring or sequelae,” she said.

Infantile acne begins about 3-6 months of age typically, or a little bit older, and lasts up to 2 years of age, Dr. Zaenglein said. “You will see comedones in infantile acne, so this is actually a true form of acne. It’s due to increased adrenal production of androgens.”

She added: “The scarring can be permanent. It’s important that you recognize infantile acne and treat it, even though it seems pretty mild.”

For infantile acne, she recommends performing a full-skin exam to rule out hyperandrogenic disorders such as Cushing syndrome, congenital adrenal hyperplasia, premature adrenarche, a gonadal/adrenal tumor and precocious puberty.

Treatments are similar to those in teenagers, she said, “but make sure you use baby-friendly formulations,” with lower concentrations of active ingredients – and avoid tetracyclines and benzoyl peroxide (BPO) washes. BPO can be used in leave-on formulations/creams at lower strengths (2.5%-5%).

One possible combination option is tretinoin 0.025% cream or adapalene 0.1% gel plus BPO 2.5% cream or clindamycin/BPO gel. Another combination is adapalene/BPO 2.5% gel.

Erythromycin can be appropriate at 30-50 mg/kg per day divided in two or three doses a day, but beware of possible gastrointestinal upset. Azithromycin at 5 mg/kg per day is another option.

“Rarely do we have to go to isotretinoin,” Dr. Zaenglein said. “I think in all my years, I’ve only treated one baby with isotretinoin for infantile acne. But severe forms can occur.”

Midchildhood and preadolescent acne conditions occur in children starting at ages 1 up to 10 years, Dr. Zaenglein said. In this population, she also recommends ruling out hyperandrogenism by looking for secondary sexual characteristics with full-body skin exams. “The workup can be broad and includes looking at adrenal androgens and total and free testosterone, as well as looking at growth charts and bone age. Typically, you’ll refer these kids to pediatric endocrinology.”

Keep in mind, she said, that early adrenarche starts at ages 6-7 years in girls and 7-8 years in boys. “That’s when we expect to start seeing that very early acne. You can see it even earlier in patients with elevated BMI, and it’s more common in Hispanic and Black children as well.”

She added that it’s important to remember that early adrenarche is a risk factor for polycystic ovarian syndrome (PCOS). “So ask patients about their family history and look for other signs of PCOS as they move further into adolescence.”

Milder cases of acne in this age group can be treated with “salicylic acid wipes and things that are kind of a rite of passage. But if they have any more severe acne, you’re going to want to treat it more or less like you do adolescent acne.”

MedscapeLive and this news organization are owned by the same parent company. Dr. Zaenglein disclosed receiving consulting fees from Cassiopea, Dermata, and Regeneron and fees for contracted research support from Incyte.

Eczema herpeticum and staphylococcal scalded skin syndrome can be emergencies in children and require immediate care, warned dermatologist George Hightower, MD, PhD, in a presentation at MedscapeLive’s virtual Women’s & Pediatric Dermatology Seminar.

Eczema herpeticum is a condition in which a herpes simplex virus (HSV-1 or HSV-2) is superimposed over preexisting eczema. “The infection may be primary and sustained from a close contact or result in some of our older patients from reactivation and spread through autoinoculation,” said Dr. Hightower, of Rady Children’s Hospital and the University of California, both in San Diego.

Signs, he said, include acute worsening of atopic dermatitis with new-onset vesicles, pustules, and “punched-out” hemorrhagic crusted erosions. “Presentation ranges from mild to transient to life threatening.”

Potential complications include meningitis, encephalitis, hepatitis, and chronic conjunctivitis. “That’s why immediate ophthalmological evaluation is needed when there’s involvement on the face near the eye,” he said.

As for management and care, “where I have concern for HSV patients, I get HSV [polymerase chain reaction] as well as a bacterial culture,” he said. But even before the results are available, empiric treatment with acyclovir can be appropriate. “It’s got to be systemic for these kids with severe involvement,” he said, and they should also be started on medication for staphylococci and streptococci.

During his presentation, Dr. Hightower also highlighted staphylococcal scalded skin syndrome. Patients with the disease commonly have concurrent skin pain (which can appear to be fussiness), fever, irritability, malaise, and poor feeding. Examination may reveal widespread erythema with accentuation at folds/peeling at hands and large sheets of superficial peeling scale with diffuse erythema.

Widespread skin involvement “results not from the presence of staph throughout the skin, but the exotoxin that it produces that becomes systemic,” he said. “Clinical diagnosis is supported by presence of S. aureus on bacterial culture, but the presence of staph is not necessary to make the diagnosis. When in doubt, histopathology is helpful. But again, it’s not necessary to make the diagnosis.”

Cases can be managed with a first- or second-generation cephalosporin, he said. Alternative therapies include antistaphylococcus penicillinase-resistant penicillins (oxacillin or nafcillin) or vancomycin.

While Dr. Hightower doesn’t use clindamycin in these patients, he said it’s an option that some dermatologists consider because of its antistaphylococcus activity. “Historically, people thought it may decrease exotoxin production. The big concern if you are going to use clindamycin is that there are high rates of community resistance,” he said. “So you want to be careful that you know your resistance patterns wherever you are. Follow up on culture to make sure that you have adequate coverage for the bug that the kiddo in front of you has.”

Dr. Hightower reported no relevant disclosures. MedscapeLive and this news organization are owned by the same parent company.

Eczema herpeticum and staphylococcal scalded skin syndrome can be emergencies in children and require immediate care, warned dermatologist George Hightower, MD, PhD, in a presentation at MedscapeLive’s virtual Women’s & Pediatric Dermatology Seminar.

Eczema herpeticum is a condition in which a herpes simplex virus (HSV-1 or HSV-2) is superimposed over preexisting eczema. “The infection may be primary and sustained from a close contact or result in some of our older patients from reactivation and spread through autoinoculation,” said Dr. Hightower, of Rady Children’s Hospital and the University of California, both in San Diego.

Signs, he said, include acute worsening of atopic dermatitis with new-onset vesicles, pustules, and “punched-out” hemorrhagic crusted erosions. “Presentation ranges from mild to transient to life threatening.”

Potential complications include meningitis, encephalitis, hepatitis, and chronic conjunctivitis. “That’s why immediate ophthalmological evaluation is needed when there’s involvement on the face near the eye,” he said.

As for management and care, “where I have concern for HSV patients, I get HSV [polymerase chain reaction] as well as a bacterial culture,” he said. But even before the results are available, empiric treatment with acyclovir can be appropriate. “It’s got to be systemic for these kids with severe involvement,” he said, and they should also be started on medication for staphylococci and streptococci.

During his presentation, Dr. Hightower also highlighted staphylococcal scalded skin syndrome. Patients with the disease commonly have concurrent skin pain (which can appear to be fussiness), fever, irritability, malaise, and poor feeding. Examination may reveal widespread erythema with accentuation at folds/peeling at hands and large sheets of superficial peeling scale with diffuse erythema.

Widespread skin involvement “results not from the presence of staph throughout the skin, but the exotoxin that it produces that becomes systemic,” he said. “Clinical diagnosis is supported by presence of S. aureus on bacterial culture, but the presence of staph is not necessary to make the diagnosis. When in doubt, histopathology is helpful. But again, it’s not necessary to make the diagnosis.”

Cases can be managed with a first- or second-generation cephalosporin, he said. Alternative therapies include antistaphylococcus penicillinase-resistant penicillins (oxacillin or nafcillin) or vancomycin.

While Dr. Hightower doesn’t use clindamycin in these patients, he said it’s an option that some dermatologists consider because of its antistaphylococcus activity. “Historically, people thought it may decrease exotoxin production. The big concern if you are going to use clindamycin is that there are high rates of community resistance,” he said. “So you want to be careful that you know your resistance patterns wherever you are. Follow up on culture to make sure that you have adequate coverage for the bug that the kiddo in front of you has.”

Dr. Hightower reported no relevant disclosures. MedscapeLive and this news organization are owned by the same parent company.

Eczema herpeticum and staphylococcal scalded skin syndrome can be emergencies in children and require immediate care, warned dermatologist George Hightower, MD, PhD, in a presentation at MedscapeLive’s virtual Women’s & Pediatric Dermatology Seminar.

Eczema herpeticum is a condition in which a herpes simplex virus (HSV-1 or HSV-2) is superimposed over preexisting eczema. “The infection may be primary and sustained from a close contact or result in some of our older patients from reactivation and spread through autoinoculation,” said Dr. Hightower, of Rady Children’s Hospital and the University of California, both in San Diego.

Signs, he said, include acute worsening of atopic dermatitis with new-onset vesicles, pustules, and “punched-out” hemorrhagic crusted erosions. “Presentation ranges from mild to transient to life threatening.”

Potential complications include meningitis, encephalitis, hepatitis, and chronic conjunctivitis. “That’s why immediate ophthalmological evaluation is needed when there’s involvement on the face near the eye,” he said.

As for management and care, “where I have concern for HSV patients, I get HSV [polymerase chain reaction] as well as a bacterial culture,” he said. But even before the results are available, empiric treatment with acyclovir can be appropriate. “It’s got to be systemic for these kids with severe involvement,” he said, and they should also be started on medication for staphylococci and streptococci.

During his presentation, Dr. Hightower also highlighted staphylococcal scalded skin syndrome. Patients with the disease commonly have concurrent skin pain (which can appear to be fussiness), fever, irritability, malaise, and poor feeding. Examination may reveal widespread erythema with accentuation at folds/peeling at hands and large sheets of superficial peeling scale with diffuse erythema.

Widespread skin involvement “results not from the presence of staph throughout the skin, but the exotoxin that it produces that becomes systemic,” he said. “Clinical diagnosis is supported by presence of S. aureus on bacterial culture, but the presence of staph is not necessary to make the diagnosis. When in doubt, histopathology is helpful. But again, it’s not necessary to make the diagnosis.”

Cases can be managed with a first- or second-generation cephalosporin, he said. Alternative therapies include antistaphylococcus penicillinase-resistant penicillins (oxacillin or nafcillin) or vancomycin.

While Dr. Hightower doesn’t use clindamycin in these patients, he said it’s an option that some dermatologists consider because of its antistaphylococcus activity. “Historically, people thought it may decrease exotoxin production. The big concern if you are going to use clindamycin is that there are high rates of community resistance,” he said. “So you want to be careful that you know your resistance patterns wherever you are. Follow up on culture to make sure that you have adequate coverage for the bug that the kiddo in front of you has.”

Dr. Hightower reported no relevant disclosures. MedscapeLive and this news organization are owned by the same parent company.

Prognoses remain extremely poor after hypomethylating agents (HMAs) fail in patients with higher-risk myelodysplastic syndromes (HR-MDS). But a hematologist-oncologist told colleagues that novel therapies are in the works, and some show promise.

Still, “the clinical development for drugs in this setting has been quite challenging, and we have had a lot of drugs that have died in this space over the years,” cautioned Amer Zeidan, MBBS, MHS, an associate professor at Yale University, New Haven, Conn., in a presentation at the virtual Acute Leukemia Forum of Hemedicus. For now, “the best way to manage HMA failure in MDS patients is by preventing HMA failure.”

Dr. Zeidan highlighted a 2016 study – which he led – that found the median overall survival from diagnosis was just a median of 17.0 months (95% confidence interval, 15.8-18.4) in 632 patients with HR-MDS. Another 2016 study, which he also led, reported median overall survival of 11 months (95% CI, 10-14) and 12 months (95% CI, 11-16; P = .26) for patients aged 66 or older who had HR-MDS and took azacitidine and decitabine, respectively. Median survival is even shorter after HMA failure, he said.

The most important obstacle to effective therapy is “the biologic and molecular heterogeneity of the disease,” he said. “Only a certain number of genes are altered in a significant number of patients. And then you have a very long tail, with so many alterations, but most of them are rare. That makes targeting all patients with the same mechanism quite challenging. Also, we poorly understand how hypomethylating agents work and the mechanism of primary and secondary failure. And many MDS patients are older with multiple conditions, multiple comorbidities. By the time of failure, they are generally beaten up and very difficult to enroll in clinical trials.”

Even so, he said, “the understanding of the molecular pathogenesis of MDS is starting to open the door for new drug development opportunities. What’s been changing over the last 5 years is an increased understanding of targeting some of the alterations that are specific to the patient – individualized targeting or precision medicine.”
 

Novel therapies

Dr. Zeidan said the novel therapies for HR-MDS after HMA failure fall into these categories: molecularly targeted agents, genetically agnostic small-molecule inhibitors, immunotherapies, and chemotherapy/epigenetic agents.

Multiple trials, for example, are examining a chemotherapy treatment CPX-351 (liposomal cytarabine-daunorubicin) in HR-MDS, and a 2018 study showed improvement in median survival in older patients with newly diagnosed secondary acute myeloid leukemia. “However, this remains an investigational treatment,” Dr. Zeidan cautioned.

Venetoclax is also being studied. Animal and cell culture data suggest there may be helpful synergistic activity between venetoclax and azacitidine in both the frontline and relapse settings. Dr. Zeidan highlighted his own 2019 report on a phase 1b study of venetoclax versus venetoclax and azacitidine in the HMA failure/HR-MDS setting. The results are “quite exciting,” he said.

The report noted that, “although the study is still ongoing, the 6-month OS [overall survival] estimate of 57% in monotherapy [patients] compares favorably to historical controls.”

Glasdegib is “another drug of interest,” although it’s mostly been studied in the frontline setting, he said, and “we don’t have much data with this drug in the refractory setting for MDS patients.” APR-246 is also intriguing, he said, but again lacks data in the refractory setting.

Dr. Zeidan noted research into other treatments – rigosertib (recent findings have been disappointing), ivosidenib for IDH1-mutated MDS, AG221-001 and enasidenib (targeting IDH2 mutations), trametinib (targeting RAS pathway mutations), and others. For now, “clinical trial participation should be the best way to manage these patients.”

Dr. Zeidan disclosed multiple disclosures, including relationships with Pfizer, Novartis, Abbvie, Pfizer, Medimmune/AstraZeneca and Boehringer Ingelheim, among others.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Prognoses remain extremely poor after hypomethylating agents (HMAs) fail in patients with higher-risk myelodysplastic syndromes (HR-MDS). But a hematologist-oncologist told colleagues that novel therapies are in the works, and some show promise.

Still, “the clinical development for drugs in this setting has been quite challenging, and we have had a lot of drugs that have died in this space over the years,” cautioned Amer Zeidan, MBBS, MHS, an associate professor at Yale University, New Haven, Conn., in a presentation at the virtual Acute Leukemia Forum of Hemedicus. For now, “the best way to manage HMA failure in MDS patients is by preventing HMA failure.”

Dr. Zeidan highlighted a 2016 study – which he led – that found the median overall survival from diagnosis was just a median of 17.0 months (95% confidence interval, 15.8-18.4) in 632 patients with HR-MDS. Another 2016 study, which he also led, reported median overall survival of 11 months (95% CI, 10-14) and 12 months (95% CI, 11-16; P = .26) for patients aged 66 or older who had HR-MDS and took azacitidine and decitabine, respectively. Median survival is even shorter after HMA failure, he said.

The most important obstacle to effective therapy is “the biologic and molecular heterogeneity of the disease,” he said. “Only a certain number of genes are altered in a significant number of patients. And then you have a very long tail, with so many alterations, but most of them are rare. That makes targeting all patients with the same mechanism quite challenging. Also, we poorly understand how hypomethylating agents work and the mechanism of primary and secondary failure. And many MDS patients are older with multiple conditions, multiple comorbidities. By the time of failure, they are generally beaten up and very difficult to enroll in clinical trials.”

Even so, he said, “the understanding of the molecular pathogenesis of MDS is starting to open the door for new drug development opportunities. What’s been changing over the last 5 years is an increased understanding of targeting some of the alterations that are specific to the patient – individualized targeting or precision medicine.”
 

Novel therapies

Dr. Zeidan said the novel therapies for HR-MDS after HMA failure fall into these categories: molecularly targeted agents, genetically agnostic small-molecule inhibitors, immunotherapies, and chemotherapy/epigenetic agents.

Multiple trials, for example, are examining a chemotherapy treatment CPX-351 (liposomal cytarabine-daunorubicin) in HR-MDS, and a 2018 study showed improvement in median survival in older patients with newly diagnosed secondary acute myeloid leukemia. “However, this remains an investigational treatment,” Dr. Zeidan cautioned.

Venetoclax is also being studied. Animal and cell culture data suggest there may be helpful synergistic activity between venetoclax and azacitidine in both the frontline and relapse settings. Dr. Zeidan highlighted his own 2019 report on a phase 1b study of venetoclax versus venetoclax and azacitidine in the HMA failure/HR-MDS setting. The results are “quite exciting,” he said.

The report noted that, “although the study is still ongoing, the 6-month OS [overall survival] estimate of 57% in monotherapy [patients] compares favorably to historical controls.”

Glasdegib is “another drug of interest,” although it’s mostly been studied in the frontline setting, he said, and “we don’t have much data with this drug in the refractory setting for MDS patients.” APR-246 is also intriguing, he said, but again lacks data in the refractory setting.

Dr. Zeidan noted research into other treatments – rigosertib (recent findings have been disappointing), ivosidenib for IDH1-mutated MDS, AG221-001 and enasidenib (targeting IDH2 mutations), trametinib (targeting RAS pathway mutations), and others. For now, “clinical trial participation should be the best way to manage these patients.”

Dr. Zeidan disclosed multiple disclosures, including relationships with Pfizer, Novartis, Abbvie, Pfizer, Medimmune/AstraZeneca and Boehringer Ingelheim, among others.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Prognoses remain extremely poor after hypomethylating agents (HMAs) fail in patients with higher-risk myelodysplastic syndromes (HR-MDS). But a hematologist-oncologist told colleagues that novel therapies are in the works, and some show promise.

Still, “the clinical development for drugs in this setting has been quite challenging, and we have had a lot of drugs that have died in this space over the years,” cautioned Amer Zeidan, MBBS, MHS, an associate professor at Yale University, New Haven, Conn., in a presentation at the virtual Acute Leukemia Forum of Hemedicus. For now, “the best way to manage HMA failure in MDS patients is by preventing HMA failure.”

Dr. Zeidan highlighted a 2016 study – which he led – that found the median overall survival from diagnosis was just a median of 17.0 months (95% confidence interval, 15.8-18.4) in 632 patients with HR-MDS. Another 2016 study, which he also led, reported median overall survival of 11 months (95% CI, 10-14) and 12 months (95% CI, 11-16; P = .26) for patients aged 66 or older who had HR-MDS and took azacitidine and decitabine, respectively. Median survival is even shorter after HMA failure, he said.

The most important obstacle to effective therapy is “the biologic and molecular heterogeneity of the disease,” he said. “Only a certain number of genes are altered in a significant number of patients. And then you have a very long tail, with so many alterations, but most of them are rare. That makes targeting all patients with the same mechanism quite challenging. Also, we poorly understand how hypomethylating agents work and the mechanism of primary and secondary failure. And many MDS patients are older with multiple conditions, multiple comorbidities. By the time of failure, they are generally beaten up and very difficult to enroll in clinical trials.”

Even so, he said, “the understanding of the molecular pathogenesis of MDS is starting to open the door for new drug development opportunities. What’s been changing over the last 5 years is an increased understanding of targeting some of the alterations that are specific to the patient – individualized targeting or precision medicine.”
 

Novel therapies

Dr. Zeidan said the novel therapies for HR-MDS after HMA failure fall into these categories: molecularly targeted agents, genetically agnostic small-molecule inhibitors, immunotherapies, and chemotherapy/epigenetic agents.

Multiple trials, for example, are examining a chemotherapy treatment CPX-351 (liposomal cytarabine-daunorubicin) in HR-MDS, and a 2018 study showed improvement in median survival in older patients with newly diagnosed secondary acute myeloid leukemia. “However, this remains an investigational treatment,” Dr. Zeidan cautioned.

Venetoclax is also being studied. Animal and cell culture data suggest there may be helpful synergistic activity between venetoclax and azacitidine in both the frontline and relapse settings. Dr. Zeidan highlighted his own 2019 report on a phase 1b study of venetoclax versus venetoclax and azacitidine in the HMA failure/HR-MDS setting. The results are “quite exciting,” he said.

The report noted that, “although the study is still ongoing, the 6-month OS [overall survival] estimate of 57% in monotherapy [patients] compares favorably to historical controls.”

Glasdegib is “another drug of interest,” although it’s mostly been studied in the frontline setting, he said, and “we don’t have much data with this drug in the refractory setting for MDS patients.” APR-246 is also intriguing, he said, but again lacks data in the refractory setting.

Dr. Zeidan noted research into other treatments – rigosertib (recent findings have been disappointing), ivosidenib for IDH1-mutated MDS, AG221-001 and enasidenib (targeting IDH2 mutations), trametinib (targeting RAS pathway mutations), and others. For now, “clinical trial participation should be the best way to manage these patients.”

Dr. Zeidan disclosed multiple disclosures, including relationships with Pfizer, Novartis, Abbvie, Pfizer, Medimmune/AstraZeneca and Boehringer Ingelheim, among others.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Hematopoietic stem cell transplantation (HCT) is one of the most important treatment options for acute leukemias. However, posttransplant cancer recurrence remains a continuing issue. And while there are reasons to think that hypomethylating agents (HMAS) could be helpful as maintenance tools to prevent cancer recurrence after HCT in leukemia, a hematologist/oncologist told colleagues that the treatment isn’t yet ready for prime time.

“I don’t think you can prefer hypomethylating agents over anything right now. Unfortunately, there’s no data that we can hang our hat on that says they are of benefit in the posttransplant setting,” said Frederick Appelbaum, MD, executive vice president and deputy director of the Fred Hutchinson Cancer Research Center, Seattle, in a presentation at the virtual Acute Leukemia Forum of Hemedicus.

However, there’s still plenty of room for improvement for patients following HCT, he said, pointing to the findings of a 2020 study. The report, which he cowrote, found that 200-day mortality after HCT fell by a third from 2003-2007 to 2013-20017, but also noted that “relapse of cancer remains the largest obstacle to better survival outcomes.”

Dr. Appelbaum described the findings this way: “Without a doubt, the major limitation to transplants for hematologic malignancies today is disease recurrence,” he said. “In fact, if you look at patients after day 100, over 60% of the reason for failure is tumor regrowth. Thus, people are very anxious to look at any method that we can to prevent posttransplant relapse, including the use of hypomethylating agents.”

In regard to strategy, “we don’t have to get rid of every last leukemic cell. Just delaying recurrence might be enough,” he said. “If you can keep the patient from relapsing for the first 3 months, and then take the brakes off the immune suppression and allow immunity to regrow, that may be enough to allow increased numbers of patients to be cured of their disease.”
 

A potential role

Why might HMAS be a possible option after transplant? They do appear to play a role after chemotherapy, he said, pointing to four 2019 studies: One that examined decitabine and three that examined azacytidine: Here, here, and here.

“These four studies provide convincing evidence that hypomethylating-agent therapy after conventional chemotherapy may either prevent or delay relapse when given as maintenance,” Dr. Appelbaum said.

If HMAS work after standard chemotherapy, why might they fail to work after transplantation? “For one, by the time the disease has been able to go through chemotherapy and transplant, you’re left with highly resistant cells,” he said. “Therefore, hypomethylating agents may not be enough to get rid of the disease. Secondly, any of you who have tried to give a maintenance therapy after transplantation know how difficult it can be with CMV [cytomegalovirus] reactivation, count suppression with ganciclovir, graft-versus-host disease [GVHD] causing nausea and vomiting, diarrhea and renal dysfunction caused by calcineurin inhibitors. These are daily events during the first 3 months after transplantation, making drug administration difficult.”

In addition, he said, “even if you can give the drug, the clinical and disease variability may make it very difficult to detect an effect.”

In another study, researchers “did make a valiant attempt to study azacitidine in the posttransplant setting by randomizing 181 patients to either azacitidine or observation,” Dr. Appelbaum said. “Unfortunately, as they reported in 2018, they could not detect a difference in either disease-free or overall survival.”

The researchers reported that nearly 75% of patients in the azacitidine arm failed to complete the planned 12 cycles of treatment, he said. “The reasons for stopping the drug were pretty profound. Half of the patients stopped because they relapsed. Others had stopped because of grades three or four toxicity, death, or severe GVHD or significant infections. It is very difficult to give the drug.”

In the future, “if we truly want to optimize the benefit of using hypomethylating agents after transplantation, it’s going to be very important for us to understand how they work,” he said. “Understanding that would then help us to select which drug we should use, what the dosing and schedule might be, and also to select patients that might benefit from it. Unfortunately, right now, it’s pretty much of a black box. We don’t really understand the effects of hypomethylating agents in the posttransplant period.”

Still, he added, “without question, the results that we have seen with the use of hypomethylating agents after conventional chemotherapy – prolonging disease-free and, probably, overall survival – are going to provide a very, very strong stimulus to study hypomethylating agents after transplantation as well.”

Dr. Appelbaum reports no disclosures.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Hematopoietic stem cell transplantation (HCT) is one of the most important treatment options for acute leukemias. However, posttransplant cancer recurrence remains a continuing issue. And while there are reasons to think that hypomethylating agents (HMAS) could be helpful as maintenance tools to prevent cancer recurrence after HCT in leukemia, a hematologist/oncologist told colleagues that the treatment isn’t yet ready for prime time.

“I don’t think you can prefer hypomethylating agents over anything right now. Unfortunately, there’s no data that we can hang our hat on that says they are of benefit in the posttransplant setting,” said Frederick Appelbaum, MD, executive vice president and deputy director of the Fred Hutchinson Cancer Research Center, Seattle, in a presentation at the virtual Acute Leukemia Forum of Hemedicus.

However, there’s still plenty of room for improvement for patients following HCT, he said, pointing to the findings of a 2020 study. The report, which he cowrote, found that 200-day mortality after HCT fell by a third from 2003-2007 to 2013-20017, but also noted that “relapse of cancer remains the largest obstacle to better survival outcomes.”

Dr. Appelbaum described the findings this way: “Without a doubt, the major limitation to transplants for hematologic malignancies today is disease recurrence,” he said. “In fact, if you look at patients after day 100, over 60% of the reason for failure is tumor regrowth. Thus, people are very anxious to look at any method that we can to prevent posttransplant relapse, including the use of hypomethylating agents.”

In regard to strategy, “we don’t have to get rid of every last leukemic cell. Just delaying recurrence might be enough,” he said. “If you can keep the patient from relapsing for the first 3 months, and then take the brakes off the immune suppression and allow immunity to regrow, that may be enough to allow increased numbers of patients to be cured of their disease.”
 

A potential role

Why might HMAS be a possible option after transplant? They do appear to play a role after chemotherapy, he said, pointing to four 2019 studies: One that examined decitabine and three that examined azacytidine: Here, here, and here.

“These four studies provide convincing evidence that hypomethylating-agent therapy after conventional chemotherapy may either prevent or delay relapse when given as maintenance,” Dr. Appelbaum said.

If HMAS work after standard chemotherapy, why might they fail to work after transplantation? “For one, by the time the disease has been able to go through chemotherapy and transplant, you’re left with highly resistant cells,” he said. “Therefore, hypomethylating agents may not be enough to get rid of the disease. Secondly, any of you who have tried to give a maintenance therapy after transplantation know how difficult it can be with CMV [cytomegalovirus] reactivation, count suppression with ganciclovir, graft-versus-host disease [GVHD] causing nausea and vomiting, diarrhea and renal dysfunction caused by calcineurin inhibitors. These are daily events during the first 3 months after transplantation, making drug administration difficult.”

In addition, he said, “even if you can give the drug, the clinical and disease variability may make it very difficult to detect an effect.”

In another study, researchers “did make a valiant attempt to study azacitidine in the posttransplant setting by randomizing 181 patients to either azacitidine or observation,” Dr. Appelbaum said. “Unfortunately, as they reported in 2018, they could not detect a difference in either disease-free or overall survival.”

The researchers reported that nearly 75% of patients in the azacitidine arm failed to complete the planned 12 cycles of treatment, he said. “The reasons for stopping the drug were pretty profound. Half of the patients stopped because they relapsed. Others had stopped because of grades three or four toxicity, death, or severe GVHD or significant infections. It is very difficult to give the drug.”

In the future, “if we truly want to optimize the benefit of using hypomethylating agents after transplantation, it’s going to be very important for us to understand how they work,” he said. “Understanding that would then help us to select which drug we should use, what the dosing and schedule might be, and also to select patients that might benefit from it. Unfortunately, right now, it’s pretty much of a black box. We don’t really understand the effects of hypomethylating agents in the posttransplant period.”

Still, he added, “without question, the results that we have seen with the use of hypomethylating agents after conventional chemotherapy – prolonging disease-free and, probably, overall survival – are going to provide a very, very strong stimulus to study hypomethylating agents after transplantation as well.”

Dr. Appelbaum reports no disclosures.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Hematopoietic stem cell transplantation (HCT) is one of the most important treatment options for acute leukemias. However, posttransplant cancer recurrence remains a continuing issue. And while there are reasons to think that hypomethylating agents (HMAS) could be helpful as maintenance tools to prevent cancer recurrence after HCT in leukemia, a hematologist/oncologist told colleagues that the treatment isn’t yet ready for prime time.

“I don’t think you can prefer hypomethylating agents over anything right now. Unfortunately, there’s no data that we can hang our hat on that says they are of benefit in the posttransplant setting,” said Frederick Appelbaum, MD, executive vice president and deputy director of the Fred Hutchinson Cancer Research Center, Seattle, in a presentation at the virtual Acute Leukemia Forum of Hemedicus.

However, there’s still plenty of room for improvement for patients following HCT, he said, pointing to the findings of a 2020 study. The report, which he cowrote, found that 200-day mortality after HCT fell by a third from 2003-2007 to 2013-20017, but also noted that “relapse of cancer remains the largest obstacle to better survival outcomes.”

Dr. Appelbaum described the findings this way: “Without a doubt, the major limitation to transplants for hematologic malignancies today is disease recurrence,” he said. “In fact, if you look at patients after day 100, over 60% of the reason for failure is tumor regrowth. Thus, people are very anxious to look at any method that we can to prevent posttransplant relapse, including the use of hypomethylating agents.”

In regard to strategy, “we don’t have to get rid of every last leukemic cell. Just delaying recurrence might be enough,” he said. “If you can keep the patient from relapsing for the first 3 months, and then take the brakes off the immune suppression and allow immunity to regrow, that may be enough to allow increased numbers of patients to be cured of their disease.”
 

A potential role

Why might HMAS be a possible option after transplant? They do appear to play a role after chemotherapy, he said, pointing to four 2019 studies: One that examined decitabine and three that examined azacytidine: Here, here, and here.

“These four studies provide convincing evidence that hypomethylating-agent therapy after conventional chemotherapy may either prevent or delay relapse when given as maintenance,” Dr. Appelbaum said.

If HMAS work after standard chemotherapy, why might they fail to work after transplantation? “For one, by the time the disease has been able to go through chemotherapy and transplant, you’re left with highly resistant cells,” he said. “Therefore, hypomethylating agents may not be enough to get rid of the disease. Secondly, any of you who have tried to give a maintenance therapy after transplantation know how difficult it can be with CMV [cytomegalovirus] reactivation, count suppression with ganciclovir, graft-versus-host disease [GVHD] causing nausea and vomiting, diarrhea and renal dysfunction caused by calcineurin inhibitors. These are daily events during the first 3 months after transplantation, making drug administration difficult.”

In addition, he said, “even if you can give the drug, the clinical and disease variability may make it very difficult to detect an effect.”

In another study, researchers “did make a valiant attempt to study azacitidine in the posttransplant setting by randomizing 181 patients to either azacitidine or observation,” Dr. Appelbaum said. “Unfortunately, as they reported in 2018, they could not detect a difference in either disease-free or overall survival.”

The researchers reported that nearly 75% of patients in the azacitidine arm failed to complete the planned 12 cycles of treatment, he said. “The reasons for stopping the drug were pretty profound. Half of the patients stopped because they relapsed. Others had stopped because of grades three or four toxicity, death, or severe GVHD or significant infections. It is very difficult to give the drug.”

In the future, “if we truly want to optimize the benefit of using hypomethylating agents after transplantation, it’s going to be very important for us to understand how they work,” he said. “Understanding that would then help us to select which drug we should use, what the dosing and schedule might be, and also to select patients that might benefit from it. Unfortunately, right now, it’s pretty much of a black box. We don’t really understand the effects of hypomethylating agents in the posttransplant period.”

Still, he added, “without question, the results that we have seen with the use of hypomethylating agents after conventional chemotherapy – prolonging disease-free and, probably, overall survival – are going to provide a very, very strong stimulus to study hypomethylating agents after transplantation as well.”

Dr. Appelbaum reports no disclosures.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Novel therapies are poised to dramatically change frontline therapy for acute myeloid leukemia (AML), and they have the potential to replace chemotherapy, a hematologist/oncologist told colleagues at the virtual Acute Leukemia Forum of Hemedicus.

But more work needs to be done, noted Alexander Perl, MD, MS, associate professor at the University of Pennsylvania, Philadelphia. While advances have transformed AML treatment in the relapsed/refractory setting, “we’re just not seeing that substantive improvement” for newly diagnosed patients, he said. “We need to find the disease-modifying drugs that work in the relapsed/refractory setting and move those frontline. That’s where we’re going to see the transformations.”

Research suggests that low-intensity therapy holds tremendous promise, he said, “with the idea that we could make therapy much more tolerable for the vast majority of patients affected by AML, who, as we know, are older patients.”

Dr. Perl highlighted the 2020 VIALE-A study – venetoclax/azacitidine versus azacitidine/placebo – which reported that “in previously untreated patients who were ineligible for intensive chemotherapy, overall survival was longer and the incidence of remission was higher among patients who received azacitidine plus venetoclax than among those who received azacitidine alone.”

Venetoclax promotes apoptosis in leukemia cells, Dr. Perl said. “To a certain extent, you can think of it as putting the rubber to the road in terms of what actually chemotherapy is designed to do, which is to make leukemic blasts apoptose. It does so without DNA damage and with much less toxicity to the patient. Therefore it can be added to any number of regimens – granted, with mild suppression, but with relatively little extramedullary toxicity.”

Dr. Perl noted that the venetoclax arm “showed a higher response rate than azacitidine in pretty much every subgroup that was looked at, whether patients had de novo leukemia, secondary leukemia, multiple mutational complements, various different karyotypes. The response rates on this study are as high as what we often will see with intensive chemotherapy.” He added that “the winning arm on this trial seems to hold up against any low-intensity therapy, and I would argue against many high-intensity therapies in older patients.”

As for other targeted agents, isocitrate dehydrogenase (IDH) inhibitors “are very promising drugs in the relapsed/refractory setting, which is primarily where these drugs are given. In regard to frontline treatment, “data are coming from a very small study, but they’re very encouraging. It’s hard to entirely say that we’re ready to change practice based on this. But it’s very encouraging – the idea that earlier use of a drug-targeting IDH mutation might lead to substantially better outcomes.”

Moving forward, he said, “we could put all of our eggs in one basket and use many active drugs [at] front line. Or we can perhaps be smart about sequencing these drugs one after another, or using more intensive approaches followed by maintenance approaches followed by more intensive approaches.”

This approach is similar to strategies in myeloma patients “who less and less are relying on an autologous transplant for durable control of their disease, and more and more are using low-intensity biologically targeted drugs,” he said.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Dr. Perl reported numerous disclosures, including relationships with Daiichi Sankyo, Abbvie, and Astellas.

Novel therapies are poised to dramatically change frontline therapy for acute myeloid leukemia (AML), and they have the potential to replace chemotherapy, a hematologist/oncologist told colleagues at the virtual Acute Leukemia Forum of Hemedicus.

But more work needs to be done, noted Alexander Perl, MD, MS, associate professor at the University of Pennsylvania, Philadelphia. While advances have transformed AML treatment in the relapsed/refractory setting, “we’re just not seeing that substantive improvement” for newly diagnosed patients, he said. “We need to find the disease-modifying drugs that work in the relapsed/refractory setting and move those frontline. That’s where we’re going to see the transformations.”

Research suggests that low-intensity therapy holds tremendous promise, he said, “with the idea that we could make therapy much more tolerable for the vast majority of patients affected by AML, who, as we know, are older patients.”

Dr. Perl highlighted the 2020 VIALE-A study – venetoclax/azacitidine versus azacitidine/placebo – which reported that “in previously untreated patients who were ineligible for intensive chemotherapy, overall survival was longer and the incidence of remission was higher among patients who received azacitidine plus venetoclax than among those who received azacitidine alone.”

Venetoclax promotes apoptosis in leukemia cells, Dr. Perl said. “To a certain extent, you can think of it as putting the rubber to the road in terms of what actually chemotherapy is designed to do, which is to make leukemic blasts apoptose. It does so without DNA damage and with much less toxicity to the patient. Therefore it can be added to any number of regimens – granted, with mild suppression, but with relatively little extramedullary toxicity.”

Dr. Perl noted that the venetoclax arm “showed a higher response rate than azacitidine in pretty much every subgroup that was looked at, whether patients had de novo leukemia, secondary leukemia, multiple mutational complements, various different karyotypes. The response rates on this study are as high as what we often will see with intensive chemotherapy.” He added that “the winning arm on this trial seems to hold up against any low-intensity therapy, and I would argue against many high-intensity therapies in older patients.”

As for other targeted agents, isocitrate dehydrogenase (IDH) inhibitors “are very promising drugs in the relapsed/refractory setting, which is primarily where these drugs are given. In regard to frontline treatment, “data are coming from a very small study, but they’re very encouraging. It’s hard to entirely say that we’re ready to change practice based on this. But it’s very encouraging – the idea that earlier use of a drug-targeting IDH mutation might lead to substantially better outcomes.”

Moving forward, he said, “we could put all of our eggs in one basket and use many active drugs [at] front line. Or we can perhaps be smart about sequencing these drugs one after another, or using more intensive approaches followed by maintenance approaches followed by more intensive approaches.”

This approach is similar to strategies in myeloma patients “who less and less are relying on an autologous transplant for durable control of their disease, and more and more are using low-intensity biologically targeted drugs,” he said.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Dr. Perl reported numerous disclosures, including relationships with Daiichi Sankyo, Abbvie, and Astellas.

Novel therapies are poised to dramatically change frontline therapy for acute myeloid leukemia (AML), and they have the potential to replace chemotherapy, a hematologist/oncologist told colleagues at the virtual Acute Leukemia Forum of Hemedicus.

But more work needs to be done, noted Alexander Perl, MD, MS, associate professor at the University of Pennsylvania, Philadelphia. While advances have transformed AML treatment in the relapsed/refractory setting, “we’re just not seeing that substantive improvement” for newly diagnosed patients, he said. “We need to find the disease-modifying drugs that work in the relapsed/refractory setting and move those frontline. That’s where we’re going to see the transformations.”

Research suggests that low-intensity therapy holds tremendous promise, he said, “with the idea that we could make therapy much more tolerable for the vast majority of patients affected by AML, who, as we know, are older patients.”

Dr. Perl highlighted the 2020 VIALE-A study – venetoclax/azacitidine versus azacitidine/placebo – which reported that “in previously untreated patients who were ineligible for intensive chemotherapy, overall survival was longer and the incidence of remission was higher among patients who received azacitidine plus venetoclax than among those who received azacitidine alone.”

Venetoclax promotes apoptosis in leukemia cells, Dr. Perl said. “To a certain extent, you can think of it as putting the rubber to the road in terms of what actually chemotherapy is designed to do, which is to make leukemic blasts apoptose. It does so without DNA damage and with much less toxicity to the patient. Therefore it can be added to any number of regimens – granted, with mild suppression, but with relatively little extramedullary toxicity.”

Dr. Perl noted that the venetoclax arm “showed a higher response rate than azacitidine in pretty much every subgroup that was looked at, whether patients had de novo leukemia, secondary leukemia, multiple mutational complements, various different karyotypes. The response rates on this study are as high as what we often will see with intensive chemotherapy.” He added that “the winning arm on this trial seems to hold up against any low-intensity therapy, and I would argue against many high-intensity therapies in older patients.”

As for other targeted agents, isocitrate dehydrogenase (IDH) inhibitors “are very promising drugs in the relapsed/refractory setting, which is primarily where these drugs are given. In regard to frontline treatment, “data are coming from a very small study, but they’re very encouraging. It’s hard to entirely say that we’re ready to change practice based on this. But it’s very encouraging – the idea that earlier use of a drug-targeting IDH mutation might lead to substantially better outcomes.”

Moving forward, he said, “we could put all of our eggs in one basket and use many active drugs [at] front line. Or we can perhaps be smart about sequencing these drugs one after another, or using more intensive approaches followed by maintenance approaches followed by more intensive approaches.”

This approach is similar to strategies in myeloma patients “who less and less are relying on an autologous transplant for durable control of their disease, and more and more are using low-intensity biologically targeted drugs,” he said.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Dr. Perl reported numerous disclosures, including relationships with Daiichi Sankyo, Abbvie, and Astellas.

Physicians are gaining a greater understanding of the pathophysiology of chronic graft-versus-host disease (cGVHD) in allo-hematopoietic cell transplantation (allo-HCT), a hematologist/oncologist told colleagues, and novel treatments are being tested.

However, options remain limited. There’s only one Food and Drug Administration–approved therapy for cGVHD that’s failed one or more treatments, and clinical trials remain a crucial option in some cases, said Mary E.D. Flowers, MD, professor of medicine at the University of Washington’s Fred Hutchinson Cancer Research Center, Seattle, in a presentation at the virtual Acute Leukemia Forum of Hemedicus.

According to Dr. Flowers, cGVHD – a product of a graft’s “immunological assault” against the person receiving a transplant – occurs in 40% of patients within a year after allo-HCT. The disorder “is associated with a poor quality of life, disability, and increased mortality after allo-transplantation,” she said. “It’s a syndrome that can be inflammatory and fibrotic. It involves several organs – the skin, the mouth, the eyes, the lungs, the GI tract.”

The median length of treatment after peripheral blood stem cell transplant is 3.5 years, Dr. Flowers said. Seven years after treatment, 10% of those who are alive – and have avoided relapse – will still need treatment. “Corticosteroids remain the first-line [treatment], at 0.5-1.0 [mg/kg], but they do not control at least 40% of the patients with cGVHD.”

In regard to pathophysiology, she highlighted a 2017 report that presented findings about the pathophysiology of cGVHD. The findings, the report authors wrote, “have yielded a raft of potential new therapeutics, centered on naive T-cell depletion, interleukin-17/21 inhibition, kinase inhibition, regulatory T-cell restoration, and CSF-1 inhibition.”

For now, no agents other than corticosteroids have shown benefit in cGVHD as initial therapy, Dr. Flowers said. In fact, several trials closed early from lack of benefit. But trials continue, she said: Results are pending for a completed phase 3 trial of ibrutinib, a Bruton tyrosine kinase inhibitor, plus steroids for initial treatment of cGVHD. Nearly 500 patients were enrolled, she said. And there’s an ongoing phase 2/3 trial of itacitinib, a Janus kinase 1 inhibitor plus steroids as initial treatment.

Dr. Flowers highlighted the case of a patient with moderate cGVHD. The patient was treated with infection prophylaxis, supportive care for oral and eyes manifestations, and prednisone 0.5 mg/kg (at a lower dose because of diabetes) plus a substitution of tacrolimus with sirolimus, a calcineurin inhibitor.

Why sirolimus? At this early point in progression, she said, the patient didn’t necessarily need systemwide chemo-suppression, and calcineurin inhibitors can be “quite effective” in management of inflammation in the liver. “It would be a completely different story once the patient develops severe cGVHR.” In that case, she said, calcineurin inhibitors wouldn’t be appropriate.

The patient’s status deteriorated to severe cGVHD, and sirolimus was replaced with ibrutinib. Other drugs were added to prevent infection and treat bronchiolitis obliterans syndrome.

In general, “the goal of the treatment is get adequate control of clinical manifestations and prevent more severe disease from developing,” Dr. Flowers said.

In response to a question about polypharmacy in patient with advanced disease – “we tend not to peel those drugs off” – Dr. Flowers said she does see new patients who appear to be taking too many medications. “They are on five drugs, and I say, ‘What are we doing?’ ”

Quite often, Dr. Flowers said, she doesn’t add therapies to existing ones but instead looks for substitutes. “A clinical lesson that I feel that I learned over time is: Ask your questions first. What would you like to see in 3 months? Or 6 months? Before you just add another therapy, do you really know what the trajectory of a disease might be?”

Dr. Flowers discloses research support (Pharmacyclics, Incyte), speaker honorarium (Janssen, Johnson & Johnson, Astellas, Mallinckrodt), and consulting relationships (Pharmacyclics, CSL Behring, Fresenius Kabi).

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Physicians are gaining a greater understanding of the pathophysiology of chronic graft-versus-host disease (cGVHD) in allo-hematopoietic cell transplantation (allo-HCT), a hematologist/oncologist told colleagues, and novel treatments are being tested.

However, options remain limited. There’s only one Food and Drug Administration–approved therapy for cGVHD that’s failed one or more treatments, and clinical trials remain a crucial option in some cases, said Mary E.D. Flowers, MD, professor of medicine at the University of Washington’s Fred Hutchinson Cancer Research Center, Seattle, in a presentation at the virtual Acute Leukemia Forum of Hemedicus.

According to Dr. Flowers, cGVHD – a product of a graft’s “immunological assault” against the person receiving a transplant – occurs in 40% of patients within a year after allo-HCT. The disorder “is associated with a poor quality of life, disability, and increased mortality after allo-transplantation,” she said. “It’s a syndrome that can be inflammatory and fibrotic. It involves several organs – the skin, the mouth, the eyes, the lungs, the GI tract.”

The median length of treatment after peripheral blood stem cell transplant is 3.5 years, Dr. Flowers said. Seven years after treatment, 10% of those who are alive – and have avoided relapse – will still need treatment. “Corticosteroids remain the first-line [treatment], at 0.5-1.0 [mg/kg], but they do not control at least 40% of the patients with cGVHD.”

In regard to pathophysiology, she highlighted a 2017 report that presented findings about the pathophysiology of cGVHD. The findings, the report authors wrote, “have yielded a raft of potential new therapeutics, centered on naive T-cell depletion, interleukin-17/21 inhibition, kinase inhibition, regulatory T-cell restoration, and CSF-1 inhibition.”

For now, no agents other than corticosteroids have shown benefit in cGVHD as initial therapy, Dr. Flowers said. In fact, several trials closed early from lack of benefit. But trials continue, she said: Results are pending for a completed phase 3 trial of ibrutinib, a Bruton tyrosine kinase inhibitor, plus steroids for initial treatment of cGVHD. Nearly 500 patients were enrolled, she said. And there’s an ongoing phase 2/3 trial of itacitinib, a Janus kinase 1 inhibitor plus steroids as initial treatment.

Dr. Flowers highlighted the case of a patient with moderate cGVHD. The patient was treated with infection prophylaxis, supportive care for oral and eyes manifestations, and prednisone 0.5 mg/kg (at a lower dose because of diabetes) plus a substitution of tacrolimus with sirolimus, a calcineurin inhibitor.

Why sirolimus? At this early point in progression, she said, the patient didn’t necessarily need systemwide chemo-suppression, and calcineurin inhibitors can be “quite effective” in management of inflammation in the liver. “It would be a completely different story once the patient develops severe cGVHR.” In that case, she said, calcineurin inhibitors wouldn’t be appropriate.

The patient’s status deteriorated to severe cGVHD, and sirolimus was replaced with ibrutinib. Other drugs were added to prevent infection and treat bronchiolitis obliterans syndrome.

In general, “the goal of the treatment is get adequate control of clinical manifestations and prevent more severe disease from developing,” Dr. Flowers said.

In response to a question about polypharmacy in patient with advanced disease – “we tend not to peel those drugs off” – Dr. Flowers said she does see new patients who appear to be taking too many medications. “They are on five drugs, and I say, ‘What are we doing?’ ”

Quite often, Dr. Flowers said, she doesn’t add therapies to existing ones but instead looks for substitutes. “A clinical lesson that I feel that I learned over time is: Ask your questions first. What would you like to see in 3 months? Or 6 months? Before you just add another therapy, do you really know what the trajectory of a disease might be?”

Dr. Flowers discloses research support (Pharmacyclics, Incyte), speaker honorarium (Janssen, Johnson & Johnson, Astellas, Mallinckrodt), and consulting relationships (Pharmacyclics, CSL Behring, Fresenius Kabi).

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Physicians are gaining a greater understanding of the pathophysiology of chronic graft-versus-host disease (cGVHD) in allo-hematopoietic cell transplantation (allo-HCT), a hematologist/oncologist told colleagues, and novel treatments are being tested.

However, options remain limited. There’s only one Food and Drug Administration–approved therapy for cGVHD that’s failed one or more treatments, and clinical trials remain a crucial option in some cases, said Mary E.D. Flowers, MD, professor of medicine at the University of Washington’s Fred Hutchinson Cancer Research Center, Seattle, in a presentation at the virtual Acute Leukemia Forum of Hemedicus.

According to Dr. Flowers, cGVHD – a product of a graft’s “immunological assault” against the person receiving a transplant – occurs in 40% of patients within a year after allo-HCT. The disorder “is associated with a poor quality of life, disability, and increased mortality after allo-transplantation,” she said. “It’s a syndrome that can be inflammatory and fibrotic. It involves several organs – the skin, the mouth, the eyes, the lungs, the GI tract.”

The median length of treatment after peripheral blood stem cell transplant is 3.5 years, Dr. Flowers said. Seven years after treatment, 10% of those who are alive – and have avoided relapse – will still need treatment. “Corticosteroids remain the first-line [treatment], at 0.5-1.0 [mg/kg], but they do not control at least 40% of the patients with cGVHD.”

In regard to pathophysiology, she highlighted a 2017 report that presented findings about the pathophysiology of cGVHD. The findings, the report authors wrote, “have yielded a raft of potential new therapeutics, centered on naive T-cell depletion, interleukin-17/21 inhibition, kinase inhibition, regulatory T-cell restoration, and CSF-1 inhibition.”

For now, no agents other than corticosteroids have shown benefit in cGVHD as initial therapy, Dr. Flowers said. In fact, several trials closed early from lack of benefit. But trials continue, she said: Results are pending for a completed phase 3 trial of ibrutinib, a Bruton tyrosine kinase inhibitor, plus steroids for initial treatment of cGVHD. Nearly 500 patients were enrolled, she said. And there’s an ongoing phase 2/3 trial of itacitinib, a Janus kinase 1 inhibitor plus steroids as initial treatment.

Dr. Flowers highlighted the case of a patient with moderate cGVHD. The patient was treated with infection prophylaxis, supportive care for oral and eyes manifestations, and prednisone 0.5 mg/kg (at a lower dose because of diabetes) plus a substitution of tacrolimus with sirolimus, a calcineurin inhibitor.

Why sirolimus? At this early point in progression, she said, the patient didn’t necessarily need systemwide chemo-suppression, and calcineurin inhibitors can be “quite effective” in management of inflammation in the liver. “It would be a completely different story once the patient develops severe cGVHR.” In that case, she said, calcineurin inhibitors wouldn’t be appropriate.

The patient’s status deteriorated to severe cGVHD, and sirolimus was replaced with ibrutinib. Other drugs were added to prevent infection and treat bronchiolitis obliterans syndrome.

In general, “the goal of the treatment is get adequate control of clinical manifestations and prevent more severe disease from developing,” Dr. Flowers said.

In response to a question about polypharmacy in patient with advanced disease – “we tend not to peel those drugs off” – Dr. Flowers said she does see new patients who appear to be taking too many medications. “They are on five drugs, and I say, ‘What are we doing?’ ”

Quite often, Dr. Flowers said, she doesn’t add therapies to existing ones but instead looks for substitutes. “A clinical lesson that I feel that I learned over time is: Ask your questions first. What would you like to see in 3 months? Or 6 months? Before you just add another therapy, do you really know what the trajectory of a disease might be?”

Dr. Flowers discloses research support (Pharmacyclics, Incyte), speaker honorarium (Janssen, Johnson & Johnson, Astellas, Mallinckrodt), and consulting relationships (Pharmacyclics, CSL Behring, Fresenius Kabi).

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Despite a variety of options, patients with relapsed/refractory acute myeloid leukemia (AML) continue to face poor prognoses, and a standard of care remains elusive, a hematologist/oncologist told colleagues.

“Clearly we have a problem with this group of patients,” Ehab Atallah, MD, professor of medicine at Medical College of Wisconsin, Milwaukee, said in a presentation at the virtual Acute Leukemia Forum of Hemedicus. In regard to treatments, he added, “we still have multiple unanswered questions.”

As Dr. Atallah noted, a 2018 study of 3,012 patients – in 9 successive ECOG‐ACRIN trials for newly diagnosed AML from 1984-2008 – showed poor outcomes for relapsed/refractory patients. At a median follow-up of 9.7 years, 59.1% reached first complete remission (CR1), and 58.9% of those relapsed. In the relapsed patients, the median overall survival from relapse was 0.5 years, and the overall survival (OS) over 5 years was 10%.

“Even among patients who relapsed with better prognostic factors – age < 40 and CR1 > 12 months – there was no significant OS difference between the studies,” the study noted. “In conclusion, this large cohort appears to confirm that the survival of AML patients post relapse continues to be dismal and has not improved during the past quarter of a century.”

There isn’t a clear standard of care, said Dr. Atallah, as shown by a 2014 phase 3 study of elacytarabine vs. investigator choice in relapsed/refractory AML patients. The investigators chose seven treatment options for the control arm.

So how can physicians make the best decisions about treatment? A 2018 report finds that some factors do offer guidance about how well relapsed patients will do, Dr. Atallah said, including worse prognoses for higher age (>50 years), time to relapse (< 1 year), number of cycles of treatment needed to achieve remission (more than 1), and unfavorable cytogenetics. And, he said, “practically no one is cured when their leukemia relapses without stem cell transplantation.”

Also keep comorbidities in mind, he said, and consider previous therapies – not just the ones implemented prior to their induction but from all treatments they received: “How much anthracycline did they get? Do they still have room to receive any more anthracycline? Do they have any pulmonary complications from GVHD [graft versus host disease]?”

Another tool may be helpful. A 2013 study found that geriatric assessment predicted survival for older adults with AML who took induction chemotherapy, he said. “I’m pretty sure that this geriatric assessment would also have significant prognostic information for patients with relapsed refractory AML.”

Molecular changes add to the complexity of treatment for relapsed/refractory AML, Dr. Atallah said, in light of new molecularly targeted drugs. He pointed to a 2019 study that showed a slight increase in median overall survival (9.3 months vs. 5.6 months) for gilteritinib vs. salvage chemotherapy in relapsed/refractory patients with FLT3-mutated AML. Other studies have shown limited effects of ID1 inhibitors, he said.

In the big picture, “there are many patient-, disease-, and prior-therapy-related variables that are involved in our decisions plus donor availability, social support, whether they have a transplant before, what kind of treatment they got before the functional assessment, and comorbidities. Even with the current choices for relapsed/refractory AML, the overall survival remains poor. Enrollment in clinical trials would be the best option for these patients.”

Dr. Atallah disclosed ties with Jazz, Abbvie, Takeda, Celgene, and Novartis.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

SOURCE: “Why Is There No Standard of Care for Relapsed AML?” Acute Leukemia Forum of Hemedicus, Oct. 15, 2020.

Despite a variety of options, patients with relapsed/refractory acute myeloid leukemia (AML) continue to face poor prognoses, and a standard of care remains elusive, a hematologist/oncologist told colleagues.

“Clearly we have a problem with this group of patients,” Ehab Atallah, MD, professor of medicine at Medical College of Wisconsin, Milwaukee, said in a presentation at the virtual Acute Leukemia Forum of Hemedicus. In regard to treatments, he added, “we still have multiple unanswered questions.”

As Dr. Atallah noted, a 2018 study of 3,012 patients – in 9 successive ECOG‐ACRIN trials for newly diagnosed AML from 1984-2008 – showed poor outcomes for relapsed/refractory patients. At a median follow-up of 9.7 years, 59.1% reached first complete remission (CR1), and 58.9% of those relapsed. In the relapsed patients, the median overall survival from relapse was 0.5 years, and the overall survival (OS) over 5 years was 10%.

“Even among patients who relapsed with better prognostic factors – age < 40 and CR1 > 12 months – there was no significant OS difference between the studies,” the study noted. “In conclusion, this large cohort appears to confirm that the survival of AML patients post relapse continues to be dismal and has not improved during the past quarter of a century.”

There isn’t a clear standard of care, said Dr. Atallah, as shown by a 2014 phase 3 study of elacytarabine vs. investigator choice in relapsed/refractory AML patients. The investigators chose seven treatment options for the control arm.

So how can physicians make the best decisions about treatment? A 2018 report finds that some factors do offer guidance about how well relapsed patients will do, Dr. Atallah said, including worse prognoses for higher age (>50 years), time to relapse (< 1 year), number of cycles of treatment needed to achieve remission (more than 1), and unfavorable cytogenetics. And, he said, “practically no one is cured when their leukemia relapses without stem cell transplantation.”

Also keep comorbidities in mind, he said, and consider previous therapies – not just the ones implemented prior to their induction but from all treatments they received: “How much anthracycline did they get? Do they still have room to receive any more anthracycline? Do they have any pulmonary complications from GVHD [graft versus host disease]?”

Another tool may be helpful. A 2013 study found that geriatric assessment predicted survival for older adults with AML who took induction chemotherapy, he said. “I’m pretty sure that this geriatric assessment would also have significant prognostic information for patients with relapsed refractory AML.”

Molecular changes add to the complexity of treatment for relapsed/refractory AML, Dr. Atallah said, in light of new molecularly targeted drugs. He pointed to a 2019 study that showed a slight increase in median overall survival (9.3 months vs. 5.6 months) for gilteritinib vs. salvage chemotherapy in relapsed/refractory patients with FLT3-mutated AML. Other studies have shown limited effects of ID1 inhibitors, he said.

In the big picture, “there are many patient-, disease-, and prior-therapy-related variables that are involved in our decisions plus donor availability, social support, whether they have a transplant before, what kind of treatment they got before the functional assessment, and comorbidities. Even with the current choices for relapsed/refractory AML, the overall survival remains poor. Enrollment in clinical trials would be the best option for these patients.”

Dr. Atallah disclosed ties with Jazz, Abbvie, Takeda, Celgene, and Novartis.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

SOURCE: “Why Is There No Standard of Care for Relapsed AML?” Acute Leukemia Forum of Hemedicus, Oct. 15, 2020.

Despite a variety of options, patients with relapsed/refractory acute myeloid leukemia (AML) continue to face poor prognoses, and a standard of care remains elusive, a hematologist/oncologist told colleagues.

“Clearly we have a problem with this group of patients,” Ehab Atallah, MD, professor of medicine at Medical College of Wisconsin, Milwaukee, said in a presentation at the virtual Acute Leukemia Forum of Hemedicus. In regard to treatments, he added, “we still have multiple unanswered questions.”

As Dr. Atallah noted, a 2018 study of 3,012 patients – in 9 successive ECOG‐ACRIN trials for newly diagnosed AML from 1984-2008 – showed poor outcomes for relapsed/refractory patients. At a median follow-up of 9.7 years, 59.1% reached first complete remission (CR1), and 58.9% of those relapsed. In the relapsed patients, the median overall survival from relapse was 0.5 years, and the overall survival (OS) over 5 years was 10%.

“Even among patients who relapsed with better prognostic factors – age < 40 and CR1 > 12 months – there was no significant OS difference between the studies,” the study noted. “In conclusion, this large cohort appears to confirm that the survival of AML patients post relapse continues to be dismal and has not improved during the past quarter of a century.”

There isn’t a clear standard of care, said Dr. Atallah, as shown by a 2014 phase 3 study of elacytarabine vs. investigator choice in relapsed/refractory AML patients. The investigators chose seven treatment options for the control arm.

So how can physicians make the best decisions about treatment? A 2018 report finds that some factors do offer guidance about how well relapsed patients will do, Dr. Atallah said, including worse prognoses for higher age (>50 years), time to relapse (< 1 year), number of cycles of treatment needed to achieve remission (more than 1), and unfavorable cytogenetics. And, he said, “practically no one is cured when their leukemia relapses without stem cell transplantation.”

Also keep comorbidities in mind, he said, and consider previous therapies – not just the ones implemented prior to their induction but from all treatments they received: “How much anthracycline did they get? Do they still have room to receive any more anthracycline? Do they have any pulmonary complications from GVHD [graft versus host disease]?”

Another tool may be helpful. A 2013 study found that geriatric assessment predicted survival for older adults with AML who took induction chemotherapy, he said. “I’m pretty sure that this geriatric assessment would also have significant prognostic information for patients with relapsed refractory AML.”

Molecular changes add to the complexity of treatment for relapsed/refractory AML, Dr. Atallah said, in light of new molecularly targeted drugs. He pointed to a 2019 study that showed a slight increase in median overall survival (9.3 months vs. 5.6 months) for gilteritinib vs. salvage chemotherapy in relapsed/refractory patients with FLT3-mutated AML. Other studies have shown limited effects of ID1 inhibitors, he said.

In the big picture, “there are many patient-, disease-, and prior-therapy-related variables that are involved in our decisions plus donor availability, social support, whether they have a transplant before, what kind of treatment they got before the functional assessment, and comorbidities. Even with the current choices for relapsed/refractory AML, the overall survival remains poor. Enrollment in clinical trials would be the best option for these patients.”

Dr. Atallah disclosed ties with Jazz, Abbvie, Takeda, Celgene, and Novartis.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

SOURCE: “Why Is There No Standard of Care for Relapsed AML?” Acute Leukemia Forum of Hemedicus, Oct. 15, 2020.

How old is too old for a patient to undergo hematopoietic cell transplantation (HCT)? That’s the wrong question to ask, a hematologist/oncologist told colleagues at the virtual Acute Leukemia Forum of Hemedicus. Instead, he said, look at other factors such as disease status and genetics.

“Transplantation for older patients, even beyond the age of 70, is acceptable, as long as it’s done with caution, care, and wisdom. So we’re all not too old for transplantation, at least not today,” said Daniel Weisdorf, MD, professor of medicine and deputy director of the University of Minnesota Clinical and Translational Science Institute.

As he noted, acute myeloid leukemia (AML) is often fatal. Among the general population, “the expected survival life expectancy at age 75 is 98% at 1 year, and most people living at 75 go on to live more than 10 years,” he said. “But if you have AML, at age 75, you have 20% survival at 1 year, 4% at 3 years. And since the median age of AML diagnosis is 68, and 75% of patients are diagnosed beyond the age of 55, this becomes relevant.”

Risk factors that affect survival after transplantation “certainly include age, but that interacts directly with the comorbidities people accumulate with age, their assessments of frailty, and their Karnofsky performance status, as well as the disease phenotype and molecular genetic markers,” Dr. Weisdorf said. “Perhaps most importantly, though not addressed very much, is patients’ willingness to undertake intensive therapy and their life outlook related to patient-reported outcomes when they get older.”

Despite the lack of indications that higher age by itself is an influential factor in survival after transplant, “we are generally reluctant to push the age of eligibility,” Dr. Weisdorf said. He noted that recently published American Society of Hematology guidelines for treatment of AML over the age of 55 “don’t discuss anything about transplantation fitness because they didn’t want to tackle that.”

Overall survival (OS) at 1 year after allogenic transplants only dipped slightly from ages 51-60 to 71 and above, according to Dr. Weisdorf’s analysis of U.S. data collected by the Center for International Blood and Marrow Transplant Research for the time period 2005-2019.

OS was 67.6% (66.8%-68.3%) for the 41-50 age group (n = 9,287) and 57.9% (56.1%-59.8%) for the 71 and older group, Dr. Weisdorf found. Overall, OS dropped by about 4 percentage points per decade of age, he said, revealing a “modest influence” of advancing years.

His analysis of autologous transplant data from the same source, also for 2005-2019, revealed “essentially no age influence.” OS was 90.8% (90.3%-91.2%) for the 41-50 age group (n = 15,075) and 86.6% (85.9%-87.3%) for the 71 and older group (n = 7,247).

Dr. Weisdorf also highlighted unpublished research that suggests that cord-blood transplant recipients older than 70 face a significantly higher risk of death than that of younger patients in the same category. Cord blood “may be option of last resort” because of a lack of other options, he explained. “And it may be part of the learning curve of cord blood transplantation, which grew a little bit in the early 2000s, and maybe past 2010, and then fell off as everybody got enamored with the haploidentical transplant option.”

How can physicians make decisions about transplants in older patients? “The transplant comorbidity index, the specific comorbidities themselves, performance score, and frailty are all measures of somebody’s fitness to be a good candidate for transplant, really at any age,” Dr. Weisdorf said. “But we also have to recognize that disease status, genetics, and the risk phenotype remain critical and should influence decision making.”

However, even as transplant survival improves overall, “very few people are incorporating any very specific biological markers” in decision-making, he said. “We’ve gotten to measures of frailty, but we haven’t gotten to any biologic measures of cytokines or other things that would predict poor chances for doing well. So I’m afraid we’re still standing at the foot of the bed saying: ‘You look okay.’ Or we’re measuring their comorbidity index. But it is disappointing that we’re using mostly very simple clinical measures to decide if somebody is sturdy enough to proceed, and we perhaps need something better. But I don’t have a great suggestion what it should be.”

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Dr. Weisdorf disclosed consulting fees from Fate Therapeutics and Incyte Corp.

SOURCE: “The Ever-Increasing Upper Age for Transplant: Is This Evidence-Based?” Acute Leukemia Forum of Hemedicus, Oct. 15, 2020.

How old is too old for a patient to undergo hematopoietic cell transplantation (HCT)? That’s the wrong question to ask, a hematologist/oncologist told colleagues at the virtual Acute Leukemia Forum of Hemedicus. Instead, he said, look at other factors such as disease status and genetics.

“Transplantation for older patients, even beyond the age of 70, is acceptable, as long as it’s done with caution, care, and wisdom. So we’re all not too old for transplantation, at least not today,” said Daniel Weisdorf, MD, professor of medicine and deputy director of the University of Minnesota Clinical and Translational Science Institute.

As he noted, acute myeloid leukemia (AML) is often fatal. Among the general population, “the expected survival life expectancy at age 75 is 98% at 1 year, and most people living at 75 go on to live more than 10 years,” he said. “But if you have AML, at age 75, you have 20% survival at 1 year, 4% at 3 years. And since the median age of AML diagnosis is 68, and 75% of patients are diagnosed beyond the age of 55, this becomes relevant.”

Risk factors that affect survival after transplantation “certainly include age, but that interacts directly with the comorbidities people accumulate with age, their assessments of frailty, and their Karnofsky performance status, as well as the disease phenotype and molecular genetic markers,” Dr. Weisdorf said. “Perhaps most importantly, though not addressed very much, is patients’ willingness to undertake intensive therapy and their life outlook related to patient-reported outcomes when they get older.”

Despite the lack of indications that higher age by itself is an influential factor in survival after transplant, “we are generally reluctant to push the age of eligibility,” Dr. Weisdorf said. He noted that recently published American Society of Hematology guidelines for treatment of AML over the age of 55 “don’t discuss anything about transplantation fitness because they didn’t want to tackle that.”

Overall survival (OS) at 1 year after allogenic transplants only dipped slightly from ages 51-60 to 71 and above, according to Dr. Weisdorf’s analysis of U.S. data collected by the Center for International Blood and Marrow Transplant Research for the time period 2005-2019.

OS was 67.6% (66.8%-68.3%) for the 41-50 age group (n = 9,287) and 57.9% (56.1%-59.8%) for the 71 and older group, Dr. Weisdorf found. Overall, OS dropped by about 4 percentage points per decade of age, he said, revealing a “modest influence” of advancing years.

His analysis of autologous transplant data from the same source, also for 2005-2019, revealed “essentially no age influence.” OS was 90.8% (90.3%-91.2%) for the 41-50 age group (n = 15,075) and 86.6% (85.9%-87.3%) for the 71 and older group (n = 7,247).

Dr. Weisdorf also highlighted unpublished research that suggests that cord-blood transplant recipients older than 70 face a significantly higher risk of death than that of younger patients in the same category. Cord blood “may be option of last resort” because of a lack of other options, he explained. “And it may be part of the learning curve of cord blood transplantation, which grew a little bit in the early 2000s, and maybe past 2010, and then fell off as everybody got enamored with the haploidentical transplant option.”

How can physicians make decisions about transplants in older patients? “The transplant comorbidity index, the specific comorbidities themselves, performance score, and frailty are all measures of somebody’s fitness to be a good candidate for transplant, really at any age,” Dr. Weisdorf said. “But we also have to recognize that disease status, genetics, and the risk phenotype remain critical and should influence decision making.”

However, even as transplant survival improves overall, “very few people are incorporating any very specific biological markers” in decision-making, he said. “We’ve gotten to measures of frailty, but we haven’t gotten to any biologic measures of cytokines or other things that would predict poor chances for doing well. So I’m afraid we’re still standing at the foot of the bed saying: ‘You look okay.’ Or we’re measuring their comorbidity index. But it is disappointing that we’re using mostly very simple clinical measures to decide if somebody is sturdy enough to proceed, and we perhaps need something better. But I don’t have a great suggestion what it should be.”

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Dr. Weisdorf disclosed consulting fees from Fate Therapeutics and Incyte Corp.

SOURCE: “The Ever-Increasing Upper Age for Transplant: Is This Evidence-Based?” Acute Leukemia Forum of Hemedicus, Oct. 15, 2020.

How old is too old for a patient to undergo hematopoietic cell transplantation (HCT)? That’s the wrong question to ask, a hematologist/oncologist told colleagues at the virtual Acute Leukemia Forum of Hemedicus. Instead, he said, look at other factors such as disease status and genetics.

“Transplantation for older patients, even beyond the age of 70, is acceptable, as long as it’s done with caution, care, and wisdom. So we’re all not too old for transplantation, at least not today,” said Daniel Weisdorf, MD, professor of medicine and deputy director of the University of Minnesota Clinical and Translational Science Institute.

As he noted, acute myeloid leukemia (AML) is often fatal. Among the general population, “the expected survival life expectancy at age 75 is 98% at 1 year, and most people living at 75 go on to live more than 10 years,” he said. “But if you have AML, at age 75, you have 20% survival at 1 year, 4% at 3 years. And since the median age of AML diagnosis is 68, and 75% of patients are diagnosed beyond the age of 55, this becomes relevant.”

Risk factors that affect survival after transplantation “certainly include age, but that interacts directly with the comorbidities people accumulate with age, their assessments of frailty, and their Karnofsky performance status, as well as the disease phenotype and molecular genetic markers,” Dr. Weisdorf said. “Perhaps most importantly, though not addressed very much, is patients’ willingness to undertake intensive therapy and their life outlook related to patient-reported outcomes when they get older.”

Despite the lack of indications that higher age by itself is an influential factor in survival after transplant, “we are generally reluctant to push the age of eligibility,” Dr. Weisdorf said. He noted that recently published American Society of Hematology guidelines for treatment of AML over the age of 55 “don’t discuss anything about transplantation fitness because they didn’t want to tackle that.”

Overall survival (OS) at 1 year after allogenic transplants only dipped slightly from ages 51-60 to 71 and above, according to Dr. Weisdorf’s analysis of U.S. data collected by the Center for International Blood and Marrow Transplant Research for the time period 2005-2019.

OS was 67.6% (66.8%-68.3%) for the 41-50 age group (n = 9,287) and 57.9% (56.1%-59.8%) for the 71 and older group, Dr. Weisdorf found. Overall, OS dropped by about 4 percentage points per decade of age, he said, revealing a “modest influence” of advancing years.

His analysis of autologous transplant data from the same source, also for 2005-2019, revealed “essentially no age influence.” OS was 90.8% (90.3%-91.2%) for the 41-50 age group (n = 15,075) and 86.6% (85.9%-87.3%) for the 71 and older group (n = 7,247).

Dr. Weisdorf also highlighted unpublished research that suggests that cord-blood transplant recipients older than 70 face a significantly higher risk of death than that of younger patients in the same category. Cord blood “may be option of last resort” because of a lack of other options, he explained. “And it may be part of the learning curve of cord blood transplantation, which grew a little bit in the early 2000s, and maybe past 2010, and then fell off as everybody got enamored with the haploidentical transplant option.”

How can physicians make decisions about transplants in older patients? “The transplant comorbidity index, the specific comorbidities themselves, performance score, and frailty are all measures of somebody’s fitness to be a good candidate for transplant, really at any age,” Dr. Weisdorf said. “But we also have to recognize that disease status, genetics, and the risk phenotype remain critical and should influence decision making.”

However, even as transplant survival improves overall, “very few people are incorporating any very specific biological markers” in decision-making, he said. “We’ve gotten to measures of frailty, but we haven’t gotten to any biologic measures of cytokines or other things that would predict poor chances for doing well. So I’m afraid we’re still standing at the foot of the bed saying: ‘You look okay.’ Or we’re measuring their comorbidity index. But it is disappointing that we’re using mostly very simple clinical measures to decide if somebody is sturdy enough to proceed, and we perhaps need something better. But I don’t have a great suggestion what it should be.”

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Dr. Weisdorf disclosed consulting fees from Fate Therapeutics and Incyte Corp.

SOURCE: “The Ever-Increasing Upper Age for Transplant: Is This Evidence-Based?” Acute Leukemia Forum of Hemedicus, Oct. 15, 2020.

The National Academies of Science, Engineering, and Medicine have just released a 522-page report, but it’s not the usual compilation of guidelines for treatment of a disease. Instead, the authors of “Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action” argue in stark terms that the American society has colossally failed individuals living with sickle cell disease (SCD), who are mostly Black or Brown. A dramatic overhaul of the country’s medical and societal priorities is needed to turn things around to improve health and longevity among this rare disease population.

Courtesy Wikimedia Commons/Osaro Erhabor/Creative Commons License

The findings from the NASEM report are explicit: “There has been substantial success in increasing the survival of children with SCD, but this success had not been translated to similar success as they become adults.” One factor posited to contribute to the slow progress in the improvement of quality and quantity of life for adults living with this disease is the fact that “SCD is largely a disease of African Americans, and as such exists in a context of racial discrimination, health and other societal disparities, mistrust of the health care system, and the effects of poverty.” The report also cites the substantial evidence that those with SCD may receive poorer quality of care.

The report’s 14 authors were made up of an ad hoc committee formed at the request of the Department of Health & Human Services’ Office of Minority Health. The office asked NASEM to convene the committee to develop a strategic plan and blueprint for the United States and others regarding SCD.

The NASEM SCD committee members “realized that we can’t address the medical components of SCD if we don’t explore societal issues and why it’s been so hard to get good care for people with sickle cell disease,” hematologist and report coauthor Ifeyinwa (Ify) Osunkwo, MD, professor of medicine and pediatrics at Atrium Health and director of the Sickle Cell Disease Enterprise, Levine Cancer Institute, Charlotte, N.C., said in an interview. Dr. Osunkwo is also the medical editor of Hematology News.

“After almost a year of meetings and digging into the background and history of SCD care, we came out with very comprehensive summary of where we were and where we want to be,” she said. “The report provides short-, intermediate- and long-term recommendations and identifies which entity and organization should be responsible for implementing them.”

The report authors, led by pediatrician and committee chair Marie Clare McCormick, MD, of the Harvard School of Public Health, Boston, stated that about 100,000 people in the United States and millions worldwide live with SCD. The disease kills more than 700 people per year in the United States, and treatment costs an estimated $2 billion a year.

When judged by disability-adjusted life-years lost – a measurement of expected healthy years of life without an illness – the impact of SCD on individuals is estimated to be greater than a long list of other diseases such as Alzheimer’s disease, breast cancer, type 1 diabetes, and AIDS/HIV, the report noted.

“The health care needs of individuals living with SCD have been neglected by the U.S. and global health care systems, causing them and their families to suffer,” the report said. “Many of the complications that afflict individuals with SCD, particularly pain, are invisible. Pain is only diagnosed by self-reports, and in SCD there are few to no external indicators of the pain experience. Nevertheless, the pain can be excruciatingly severe and requires treatment with strong analgesics.”

There’s even more misery to the story of SCD, the report said, and Dr. Osunkwo agreed. “It’s not just about pain. These individuals suffer from multiple organ-system complications that are physical but also psychological and societal. They experience a lot of disparities in every aspect of their lives. You’re sick, so then you can’t get a job or health insurance, you can’t get Social Security benefits. You can’t get the type of health care you need nor can you access the other forms of support you need and often you are judged as a drug seeker for complaining of pain or repeatedly seeking acute care for unresolved pain.”

Multiple factors exacerbate the experience of people living with SCD in America, the report said. “Because of systemic racism, unconscious bias, and the stigma associated with the diagnosis, the disease brings with it a much broader burden.”

Dr. Osunkwo put it this way: “SCD is a disease that mostly affects Brown and Black people, and that gets layered into the whole discrimination issues that Black and Brown people face compounding the health burden from their disease.”

The report added that “the SCD community has developed a significant lack of trust in the health care system due to the nearly universal stigma and lack of belief in their reports of pain, a lack of trust that has been further reinforced by historical events, such as the Tuskegee experiment.”

The report highlighted research that finds that Blacks “are more likely to receive a lower quality of pain management than white patients and may be perceived as having drug-seeking behavior.”

The report also identified gaps in treatment, noting that “many SCD complications are not restricted to any one organ system, and the impact of the disease on [quality of life] can be profound but hard to define and compartmentalize.”

Dr. Osunkwo said medical professionals often fail to understand the full breadth of the disease. “There’s no particular look to SCD. When you have cancer, you come in, and you look like you’re sick because you’re bald. Everyone clues into that cancer look and knows it’s lethal, that you’re may likely die early. We don’t have that “look that generates empathy” for SCD, and people don’t understand the burden on those affected. They don’t understand or appreciate that SCD shortens your lifespan as well ... that people living with SCD die 3 decades earlier than their ethnically matched peers. Also, SCD is associated with a lot of pain, and pain and the treatment of pain with opioids makes people [health care providers] uncomfortable unless it’s cancer pain.”

She added: “People also assume that, if it’s not pain, it’s not SCD even though SCD can cause leg ulcers and blood clots and even affect the tonsils, or lead to a stroke. When a disease complexity is too difficult for providers to understand, they either avoid it or don’t do anything for the patient.”

Screening and surveillance for SCD and sickle cell trait is insufficient, the report said, and the potential cost of missed childhood cases is large. Detecting the condition at birth allows the implementation of appropriate comprehensive care and treatment to prevent early death from infections and strokes. As the authors noted, “tremendous strides have been made in the past few decades in the care of children with SCD, which have led to almost all children in high-income settings surviving to adulthood.” However, there remains gaps in care coordination and follow-up of babies screened at birth and even bigger gaps in translating these life span gains to adults particularly around the period of transition from pediatrics to adult care when there appears to be a spike in morbidity and mortality.

Dr_Microbe/Thinkstock

The report summarized current treatments for SCD and noted “an influx of pipeline products” after years of little progress and identifies “a need for targeted SCD therapies that address the underlying cause of the disease.”

While treatment recommendations exist, Dr. Osunkwo said, “the evidence for them is very poor and many SCD complications have no evidence-based guidelines for providers to follow. We need more research to provide high quality evidence to make guidelines for SCD treatment stronger and more robust.”

In its final section, the report offers a “strategic plan and blueprint for sickle cell disease action.” It offers several strategies to achieve the vision of “long healthy productive lives for those living with sickle cell disease and sickle cell trait”:

• Establish and fund a research agenda to inform effective programs and policies across the life span.
• Implement efforts to advance understanding of the full impact of sickle cell trait on individuals and society.
• Address barriers to accessing current and pipeline therapies for SCD.
• Improve SCD awareness and strengthen advocacy efforts.
• Increase the number of qualified health professionals providing SCD care.
• Strengthen the evidence base for interventions and disease management and implement widespread efforts to monitor the quality of SCD care.
• Establish organized systems of care assuring both clinical and nonclinical supportive services to all persons living with SCD.
• Establish a national system to collect and link data to characterize the burden of disease, outcomes, and the needs of those with SCD across the life span.

“Right now, the average lifespan for SCD is in the mid-40s to mid-50s,” Dr. Osunkwo said. “That’s a horrible statistic. Even if we just take up half of these recommendations, people will live longer with SCD, and they’ll be more productive and contribute more to society. If we value a cancer life the same as a sickle cell life, we’ll be halfway across the finish line. But the stigma of SCD being a Black and Brown problem is going to be the hardest to confront as it requires a systemic change in our culture as a country and a health care system.”

Still, she said, the commissioning of the report “shows that there is a desire to understand the issue in better detail and try to mitigate it.”

Dr. Osunkwo and Dr. McCormick had no relevant disclosures.

SOURCE: National Academies of Sciences, Engineering, and Medicine. Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action. Washington, D.C.: National Academies Press, 2020.

The National Academies of Science, Engineering, and Medicine have just released a 522-page report, but it’s not the usual compilation of guidelines for treatment of a disease. Instead, the authors of “Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action” argue in stark terms that the American society has colossally failed individuals living with sickle cell disease (SCD), who are mostly Black or Brown. A dramatic overhaul of the country’s medical and societal priorities is needed to turn things around to improve health and longevity among this rare disease population.

Courtesy Wikimedia Commons/Osaro Erhabor/Creative Commons License

The findings from the NASEM report are explicit: “There has been substantial success in increasing the survival of children with SCD, but this success had not been translated to similar success as they become adults.” One factor posited to contribute to the slow progress in the improvement of quality and quantity of life for adults living with this disease is the fact that “SCD is largely a disease of African Americans, and as such exists in a context of racial discrimination, health and other societal disparities, mistrust of the health care system, and the effects of poverty.” The report also cites the substantial evidence that those with SCD may receive poorer quality of care.

The report’s 14 authors were made up of an ad hoc committee formed at the request of the Department of Health & Human Services’ Office of Minority Health. The office asked NASEM to convene the committee to develop a strategic plan and blueprint for the United States and others regarding SCD.

The NASEM SCD committee members “realized that we can’t address the medical components of SCD if we don’t explore societal issues and why it’s been so hard to get good care for people with sickle cell disease,” hematologist and report coauthor Ifeyinwa (Ify) Osunkwo, MD, professor of medicine and pediatrics at Atrium Health and director of the Sickle Cell Disease Enterprise, Levine Cancer Institute, Charlotte, N.C., said in an interview. Dr. Osunkwo is also the medical editor of Hematology News.

“After almost a year of meetings and digging into the background and history of SCD care, we came out with very comprehensive summary of where we were and where we want to be,” she said. “The report provides short-, intermediate- and long-term recommendations and identifies which entity and organization should be responsible for implementing them.”

The report authors, led by pediatrician and committee chair Marie Clare McCormick, MD, of the Harvard School of Public Health, Boston, stated that about 100,000 people in the United States and millions worldwide live with SCD. The disease kills more than 700 people per year in the United States, and treatment costs an estimated $2 billion a year.

When judged by disability-adjusted life-years lost – a measurement of expected healthy years of life without an illness – the impact of SCD on individuals is estimated to be greater than a long list of other diseases such as Alzheimer’s disease, breast cancer, type 1 diabetes, and AIDS/HIV, the report noted.

“The health care needs of individuals living with SCD have been neglected by the U.S. and global health care systems, causing them and their families to suffer,” the report said. “Many of the complications that afflict individuals with SCD, particularly pain, are invisible. Pain is only diagnosed by self-reports, and in SCD there are few to no external indicators of the pain experience. Nevertheless, the pain can be excruciatingly severe and requires treatment with strong analgesics.”

There’s even more misery to the story of SCD, the report said, and Dr. Osunkwo agreed. “It’s not just about pain. These individuals suffer from multiple organ-system complications that are physical but also psychological and societal. They experience a lot of disparities in every aspect of their lives. You’re sick, so then you can’t get a job or health insurance, you can’t get Social Security benefits. You can’t get the type of health care you need nor can you access the other forms of support you need and often you are judged as a drug seeker for complaining of pain or repeatedly seeking acute care for unresolved pain.”

Multiple factors exacerbate the experience of people living with SCD in America, the report said. “Because of systemic racism, unconscious bias, and the stigma associated with the diagnosis, the disease brings with it a much broader burden.”

Dr. Osunkwo put it this way: “SCD is a disease that mostly affects Brown and Black people, and that gets layered into the whole discrimination issues that Black and Brown people face compounding the health burden from their disease.”

The report added that “the SCD community has developed a significant lack of trust in the health care system due to the nearly universal stigma and lack of belief in their reports of pain, a lack of trust that has been further reinforced by historical events, such as the Tuskegee experiment.”

The report highlighted research that finds that Blacks “are more likely to receive a lower quality of pain management than white patients and may be perceived as having drug-seeking behavior.”

The report also identified gaps in treatment, noting that “many SCD complications are not restricted to any one organ system, and the impact of the disease on [quality of life] can be profound but hard to define and compartmentalize.”

Dr. Osunkwo said medical professionals often fail to understand the full breadth of the disease. “There’s no particular look to SCD. When you have cancer, you come in, and you look like you’re sick because you’re bald. Everyone clues into that cancer look and knows it’s lethal, that you’re may likely die early. We don’t have that “look that generates empathy” for SCD, and people don’t understand the burden on those affected. They don’t understand or appreciate that SCD shortens your lifespan as well ... that people living with SCD die 3 decades earlier than their ethnically matched peers. Also, SCD is associated with a lot of pain, and pain and the treatment of pain with opioids makes people [health care providers] uncomfortable unless it’s cancer pain.”

She added: “People also assume that, if it’s not pain, it’s not SCD even though SCD can cause leg ulcers and blood clots and even affect the tonsils, or lead to a stroke. When a disease complexity is too difficult for providers to understand, they either avoid it or don’t do anything for the patient.”

Screening and surveillance for SCD and sickle cell trait is insufficient, the report said, and the potential cost of missed childhood cases is large. Detecting the condition at birth allows the implementation of appropriate comprehensive care and treatment to prevent early death from infections and strokes. As the authors noted, “tremendous strides have been made in the past few decades in the care of children with SCD, which have led to almost all children in high-income settings surviving to adulthood.” However, there remains gaps in care coordination and follow-up of babies screened at birth and even bigger gaps in translating these life span gains to adults particularly around the period of transition from pediatrics to adult care when there appears to be a spike in morbidity and mortality.

Dr_Microbe/Thinkstock

The report summarized current treatments for SCD and noted “an influx of pipeline products” after years of little progress and identifies “a need for targeted SCD therapies that address the underlying cause of the disease.”

While treatment recommendations exist, Dr. Osunkwo said, “the evidence for them is very poor and many SCD complications have no evidence-based guidelines for providers to follow. We need more research to provide high quality evidence to make guidelines for SCD treatment stronger and more robust.”

In its final section, the report offers a “strategic plan and blueprint for sickle cell disease action.” It offers several strategies to achieve the vision of “long healthy productive lives for those living with sickle cell disease and sickle cell trait”:

• Establish and fund a research agenda to inform effective programs and policies across the life span.
• Implement efforts to advance understanding of the full impact of sickle cell trait on individuals and society.
• Address barriers to accessing current and pipeline therapies for SCD.
• Improve SCD awareness and strengthen advocacy efforts.
• Increase the number of qualified health professionals providing SCD care.
• Strengthen the evidence base for interventions and disease management and implement widespread efforts to monitor the quality of SCD care.
• Establish organized systems of care assuring both clinical and nonclinical supportive services to all persons living with SCD.
• Establish a national system to collect and link data to characterize the burden of disease, outcomes, and the needs of those with SCD across the life span.

“Right now, the average lifespan for SCD is in the mid-40s to mid-50s,” Dr. Osunkwo said. “That’s a horrible statistic. Even if we just take up half of these recommendations, people will live longer with SCD, and they’ll be more productive and contribute more to society. If we value a cancer life the same as a sickle cell life, we’ll be halfway across the finish line. But the stigma of SCD being a Black and Brown problem is going to be the hardest to confront as it requires a systemic change in our culture as a country and a health care system.”

Still, she said, the commissioning of the report “shows that there is a desire to understand the issue in better detail and try to mitigate it.”

Dr. Osunkwo and Dr. McCormick had no relevant disclosures.

SOURCE: National Academies of Sciences, Engineering, and Medicine. Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action. Washington, D.C.: National Academies Press, 2020.

The National Academies of Science, Engineering, and Medicine have just released a 522-page report, but it’s not the usual compilation of guidelines for treatment of a disease. Instead, the authors of “Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action” argue in stark terms that the American society has colossally failed individuals living with sickle cell disease (SCD), who are mostly Black or Brown. A dramatic overhaul of the country’s medical and societal priorities is needed to turn things around to improve health and longevity among this rare disease population.

Courtesy Wikimedia Commons/Osaro Erhabor/Creative Commons License

The findings from the NASEM report are explicit: “There has been substantial success in increasing the survival of children with SCD, but this success had not been translated to similar success as they become adults.” One factor posited to contribute to the slow progress in the improvement of quality and quantity of life for adults living with this disease is the fact that “SCD is largely a disease of African Americans, and as such exists in a context of racial discrimination, health and other societal disparities, mistrust of the health care system, and the effects of poverty.” The report also cites the substantial evidence that those with SCD may receive poorer quality of care.

The report’s 14 authors were made up of an ad hoc committee formed at the request of the Department of Health & Human Services’ Office of Minority Health. The office asked NASEM to convene the committee to develop a strategic plan and blueprint for the United States and others regarding SCD.

The NASEM SCD committee members “realized that we can’t address the medical components of SCD if we don’t explore societal issues and why it’s been so hard to get good care for people with sickle cell disease,” hematologist and report coauthor Ifeyinwa (Ify) Osunkwo, MD, professor of medicine and pediatrics at Atrium Health and director of the Sickle Cell Disease Enterprise, Levine Cancer Institute, Charlotte, N.C., said in an interview. Dr. Osunkwo is also the medical editor of Hematology News.

“After almost a year of meetings and digging into the background and history of SCD care, we came out with very comprehensive summary of where we were and where we want to be,” she said. “The report provides short-, intermediate- and long-term recommendations and identifies which entity and organization should be responsible for implementing them.”

The report authors, led by pediatrician and committee chair Marie Clare McCormick, MD, of the Harvard School of Public Health, Boston, stated that about 100,000 people in the United States and millions worldwide live with SCD. The disease kills more than 700 people per year in the United States, and treatment costs an estimated $2 billion a year.

When judged by disability-adjusted life-years lost – a measurement of expected healthy years of life without an illness – the impact of SCD on individuals is estimated to be greater than a long list of other diseases such as Alzheimer’s disease, breast cancer, type 1 diabetes, and AIDS/HIV, the report noted.

“The health care needs of individuals living with SCD have been neglected by the U.S. and global health care systems, causing them and their families to suffer,” the report said. “Many of the complications that afflict individuals with SCD, particularly pain, are invisible. Pain is only diagnosed by self-reports, and in SCD there are few to no external indicators of the pain experience. Nevertheless, the pain can be excruciatingly severe and requires treatment with strong analgesics.”

There’s even more misery to the story of SCD, the report said, and Dr. Osunkwo agreed. “It’s not just about pain. These individuals suffer from multiple organ-system complications that are physical but also psychological and societal. They experience a lot of disparities in every aspect of their lives. You’re sick, so then you can’t get a job or health insurance, you can’t get Social Security benefits. You can’t get the type of health care you need nor can you access the other forms of support you need and often you are judged as a drug seeker for complaining of pain or repeatedly seeking acute care for unresolved pain.”

Multiple factors exacerbate the experience of people living with SCD in America, the report said. “Because of systemic racism, unconscious bias, and the stigma associated with the diagnosis, the disease brings with it a much broader burden.”

Dr. Osunkwo put it this way: “SCD is a disease that mostly affects Brown and Black people, and that gets layered into the whole discrimination issues that Black and Brown people face compounding the health burden from their disease.”

The report added that “the SCD community has developed a significant lack of trust in the health care system due to the nearly universal stigma and lack of belief in their reports of pain, a lack of trust that has been further reinforced by historical events, such as the Tuskegee experiment.”

The report highlighted research that finds that Blacks “are more likely to receive a lower quality of pain management than white patients and may be perceived as having drug-seeking behavior.”

The report also identified gaps in treatment, noting that “many SCD complications are not restricted to any one organ system, and the impact of the disease on [quality of life] can be profound but hard to define and compartmentalize.”

Dr. Osunkwo said medical professionals often fail to understand the full breadth of the disease. “There’s no particular look to SCD. When you have cancer, you come in, and you look like you’re sick because you’re bald. Everyone clues into that cancer look and knows it’s lethal, that you’re may likely die early. We don’t have that “look that generates empathy” for SCD, and people don’t understand the burden on those affected. They don’t understand or appreciate that SCD shortens your lifespan as well ... that people living with SCD die 3 decades earlier than their ethnically matched peers. Also, SCD is associated with a lot of pain, and pain and the treatment of pain with opioids makes people [health care providers] uncomfortable unless it’s cancer pain.”

She added: “People also assume that, if it’s not pain, it’s not SCD even though SCD can cause leg ulcers and blood clots and even affect the tonsils, or lead to a stroke. When a disease complexity is too difficult for providers to understand, they either avoid it or don’t do anything for the patient.”

Screening and surveillance for SCD and sickle cell trait is insufficient, the report said, and the potential cost of missed childhood cases is large. Detecting the condition at birth allows the implementation of appropriate comprehensive care and treatment to prevent early death from infections and strokes. As the authors noted, “tremendous strides have been made in the past few decades in the care of children with SCD, which have led to almost all children in high-income settings surviving to adulthood.” However, there remains gaps in care coordination and follow-up of babies screened at birth and even bigger gaps in translating these life span gains to adults particularly around the period of transition from pediatrics to adult care when there appears to be a spike in morbidity and mortality.

Dr_Microbe/Thinkstock

The report summarized current treatments for SCD and noted “an influx of pipeline products” after years of little progress and identifies “a need for targeted SCD therapies that address the underlying cause of the disease.”

While treatment recommendations exist, Dr. Osunkwo said, “the evidence for them is very poor and many SCD complications have no evidence-based guidelines for providers to follow. We need more research to provide high quality evidence to make guidelines for SCD treatment stronger and more robust.”

In its final section, the report offers a “strategic plan and blueprint for sickle cell disease action.” It offers several strategies to achieve the vision of “long healthy productive lives for those living with sickle cell disease and sickle cell trait”:

• Establish and fund a research agenda to inform effective programs and policies across the life span.
• Implement efforts to advance understanding of the full impact of sickle cell trait on individuals and society.
• Address barriers to accessing current and pipeline therapies for SCD.
• Improve SCD awareness and strengthen advocacy efforts.
• Increase the number of qualified health professionals providing SCD care.
• Strengthen the evidence base for interventions and disease management and implement widespread efforts to monitor the quality of SCD care.
• Establish organized systems of care assuring both clinical and nonclinical supportive services to all persons living with SCD.
• Establish a national system to collect and link data to characterize the burden of disease, outcomes, and the needs of those with SCD across the life span.

“Right now, the average lifespan for SCD is in the mid-40s to mid-50s,” Dr. Osunkwo said. “That’s a horrible statistic. Even if we just take up half of these recommendations, people will live longer with SCD, and they’ll be more productive and contribute more to society. If we value a cancer life the same as a sickle cell life, we’ll be halfway across the finish line. But the stigma of SCD being a Black and Brown problem is going to be the hardest to confront as it requires a systemic change in our culture as a country and a health care system.”

Still, she said, the commissioning of the report “shows that there is a desire to understand the issue in better detail and try to mitigate it.”

Dr. Osunkwo and Dr. McCormick had no relevant disclosures.

SOURCE: National Academies of Sciences, Engineering, and Medicine. Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action. Washington, D.C.: National Academies Press, 2020.

Prognoses for patients with AIDS-associated, non-Hodgkin lymphomas (AIDS-NHLs) have improved dramatically as HIV/AIDS has become easier to treat, and “we’re actually seeing patients with long-term remissions that are translating to cure,” a hematologist told colleagues at the virtual 2020 annual meeting of the Association of VA Hematology/Oncology (AVAHO).

“Even those with low CD4 counts initially have more chance of survival compared to the historic patients in the pre-HAART [highly active antiretroviral therapy] era,” explained Erin Reid, MD, MS, of the University of California at San Diego Moores Cancer Center. “They’re seeing complete-response rates and overall-survival rates that are nearly matching what we’re seeing in the non-HIV lymphoma cases. And aggressive infection prophylaxis has seemed to mitigate some of the infectious complications.”

Still, Reid said, a severe form of AIDS-NHL continues to have very poor outcomes, although specific regimens appear to be brightening the picture somewhat.

According to Dr. Reid, AIDS-NHLs are the most common malignancy in the HIV-positive population, and patients with these cancers are more likely to have aggressive lymphomas. These patients are also more likely to have lymphomas associated with Epstein-Barr virus—40 to 80%, depending on the subtype of lymphoma—and Kaposi sarcoma-associated herpesvirus (also known as human herpesvirus-8, or HHV8).

“These viruses are driving these cancers, and it begs the question of whether there’s something we can do to target these viruses within these cancer cells in a way that’s therapeutic,” she said.

Compared with the non-HIV population, patients with AIDS-NHL “are much more likely to present with advanced stage, extranodal disease and central nervous system involvement,” she said.

HAART Benefits

It’s become clear that HIV control via HAART has benefits in terms of higher tolerance of chemotherapy doses—“we’re able to use more full or traditional dose regimens”—and perhaps cancer suppression too, she said. A 2013 meta-analysis “favored concurrent therapy with chemotherapy [and HAART]. This has become our recommended standard of care for virtually all cases, except the very rare ones where you cannot find a regimen that is compatible from a PK [pharmacokinetics] standpoint.”

Reid also noted that the HAART era has changed the role of CD4 counts in AIDS-NHLs. “While CD4 count still has some predictive value, its impact on mortality appears attenuated,” she said.

EPOCH Treatment

With regard to treatment, she emphasized the importance of HAART: “We would recommend concurrent HAART whenever possible with chemotherapy, or start it immediately afterward.”

Aggressive infection prophylaxis also is recommended through granulocyte colony-stimulating factor and agents to target threats from pneumocystis jiroveci pneumonia, gram negative rods, and varicella-zoster virus. “I’ve moved away from fungal prophylaxis over the years, only dealing with it if there’s a known fungal infection,” she said.

As for treatment of AIDS-NHL, Reid Suggested that research supports the EPOCH regimen --etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin. However, “we still need strategies for refractory and relapsed disease,” she said.

Reid noted that she has started to see more plasmablastic cases, although her experience is anecdotal. Plasmablastic lymphoma is much more common in the HIV-positive setting, she said.

Lifespans are poor for these patients, with many failing to live for a year. But research hints that the prognosis in AIDS-NHL patients on HAART may actually be better than in the non-HIV population, she said.

A trial published in September 2020, in fact, reports that 87% of 15 patients with AIDS-associated plasmablastic lymphoma survived for at least one year on the EPOCH regimen. Overall, the study found that “people with a collection of HIV-associated lymphomas were doing well overall with the EPOCH backbone,” Reid explained.

Reid reported no relevant disclosures.

Prognoses for patients with AIDS-associated, non-Hodgkin lymphomas (AIDS-NHLs) have improved dramatically as HIV/AIDS has become easier to treat, and “we’re actually seeing patients with long-term remissions that are translating to cure,” a hematologist told colleagues at the virtual 2020 annual meeting of the Association of VA Hematology/Oncology (AVAHO).

“Even those with low CD4 counts initially have more chance of survival compared to the historic patients in the pre-HAART [highly active antiretroviral therapy] era,” explained Erin Reid, MD, MS, of the University of California at San Diego Moores Cancer Center. “They’re seeing complete-response rates and overall-survival rates that are nearly matching what we’re seeing in the non-HIV lymphoma cases. And aggressive infection prophylaxis has seemed to mitigate some of the infectious complications.”

Still, Reid said, a severe form of AIDS-NHL continues to have very poor outcomes, although specific regimens appear to be brightening the picture somewhat.

According to Dr. Reid, AIDS-NHLs are the most common malignancy in the HIV-positive population, and patients with these cancers are more likely to have aggressive lymphomas. These patients are also more likely to have lymphomas associated with Epstein-Barr virus—40 to 80%, depending on the subtype of lymphoma—and Kaposi sarcoma-associated herpesvirus (also known as human herpesvirus-8, or HHV8).

“These viruses are driving these cancers, and it begs the question of whether there’s something we can do to target these viruses within these cancer cells in a way that’s therapeutic,” she said.

Compared with the non-HIV population, patients with AIDS-NHL “are much more likely to present with advanced stage, extranodal disease and central nervous system involvement,” she said.

HAART Benefits

It’s become clear that HIV control via HAART has benefits in terms of higher tolerance of chemotherapy doses—“we’re able to use more full or traditional dose regimens”—and perhaps cancer suppression too, she said. A 2013 meta-analysis “favored concurrent therapy with chemotherapy [and HAART]. This has become our recommended standard of care for virtually all cases, except the very rare ones where you cannot find a regimen that is compatible from a PK [pharmacokinetics] standpoint.”

Reid also noted that the HAART era has changed the role of CD4 counts in AIDS-NHLs. “While CD4 count still has some predictive value, its impact on mortality appears attenuated,” she said.

EPOCH Treatment

With regard to treatment, she emphasized the importance of HAART: “We would recommend concurrent HAART whenever possible with chemotherapy, or start it immediately afterward.”

Aggressive infection prophylaxis also is recommended through granulocyte colony-stimulating factor and agents to target threats from pneumocystis jiroveci pneumonia, gram negative rods, and varicella-zoster virus. “I’ve moved away from fungal prophylaxis over the years, only dealing with it if there’s a known fungal infection,” she said.

As for treatment of AIDS-NHL, Reid Suggested that research supports the EPOCH regimen --etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin. However, “we still need strategies for refractory and relapsed disease,” she said.

Reid noted that she has started to see more plasmablastic cases, although her experience is anecdotal. Plasmablastic lymphoma is much more common in the HIV-positive setting, she said.

Lifespans are poor for these patients, with many failing to live for a year. But research hints that the prognosis in AIDS-NHL patients on HAART may actually be better than in the non-HIV population, she said.

A trial published in September 2020, in fact, reports that 87% of 15 patients with AIDS-associated plasmablastic lymphoma survived for at least one year on the EPOCH regimen. Overall, the study found that “people with a collection of HIV-associated lymphomas were doing well overall with the EPOCH backbone,” Reid explained.

Reid reported no relevant disclosures.

Prognoses for patients with AIDS-associated, non-Hodgkin lymphomas (AIDS-NHLs) have improved dramatically as HIV/AIDS has become easier to treat, and “we’re actually seeing patients with long-term remissions that are translating to cure,” a hematologist told colleagues at the virtual 2020 annual meeting of the Association of VA Hematology/Oncology (AVAHO).

“Even those with low CD4 counts initially have more chance of survival compared to the historic patients in the pre-HAART [highly active antiretroviral therapy] era,” explained Erin Reid, MD, MS, of the University of California at San Diego Moores Cancer Center. “They’re seeing complete-response rates and overall-survival rates that are nearly matching what we’re seeing in the non-HIV lymphoma cases. And aggressive infection prophylaxis has seemed to mitigate some of the infectious complications.”

Still, Reid said, a severe form of AIDS-NHL continues to have very poor outcomes, although specific regimens appear to be brightening the picture somewhat.

According to Dr. Reid, AIDS-NHLs are the most common malignancy in the HIV-positive population, and patients with these cancers are more likely to have aggressive lymphomas. These patients are also more likely to have lymphomas associated with Epstein-Barr virus—40 to 80%, depending on the subtype of lymphoma—and Kaposi sarcoma-associated herpesvirus (also known as human herpesvirus-8, or HHV8).

“These viruses are driving these cancers, and it begs the question of whether there’s something we can do to target these viruses within these cancer cells in a way that’s therapeutic,” she said.

Compared with the non-HIV population, patients with AIDS-NHL “are much more likely to present with advanced stage, extranodal disease and central nervous system involvement,” she said.

HAART Benefits

It’s become clear that HIV control via HAART has benefits in terms of higher tolerance of chemotherapy doses—“we’re able to use more full or traditional dose regimens”—and perhaps cancer suppression too, she said. A 2013 meta-analysis “favored concurrent therapy with chemotherapy [and HAART]. This has become our recommended standard of care for virtually all cases, except the very rare ones where you cannot find a regimen that is compatible from a PK [pharmacokinetics] standpoint.”

Reid also noted that the HAART era has changed the role of CD4 counts in AIDS-NHLs. “While CD4 count still has some predictive value, its impact on mortality appears attenuated,” she said.

EPOCH Treatment

With regard to treatment, she emphasized the importance of HAART: “We would recommend concurrent HAART whenever possible with chemotherapy, or start it immediately afterward.”

Aggressive infection prophylaxis also is recommended through granulocyte colony-stimulating factor and agents to target threats from pneumocystis jiroveci pneumonia, gram negative rods, and varicella-zoster virus. “I’ve moved away from fungal prophylaxis over the years, only dealing with it if there’s a known fungal infection,” she said.

As for treatment of AIDS-NHL, Reid Suggested that research supports the EPOCH regimen --etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin. However, “we still need strategies for refractory and relapsed disease,” she said.

Reid noted that she has started to see more plasmablastic cases, although her experience is anecdotal. Plasmablastic lymphoma is much more common in the HIV-positive setting, she said.

Lifespans are poor for these patients, with many failing to live for a year. But research hints that the prognosis in AIDS-NHL patients on HAART may actually be better than in the non-HIV population, she said.

A trial published in September 2020, in fact, reports that 87% of 15 patients with AIDS-associated plasmablastic lymphoma survived for at least one year on the EPOCH regimen. Overall, the study found that “people with a collection of HIV-associated lymphomas were doing well overall with the EPOCH backbone,” Reid explained.

Reid reported no relevant disclosures.