AML

Atrial fibrillation (AFib) is a known and serious side effect of some cancer treatments, but it is underreported in cancer drug trials, French investigators said in a new report.

As a result, oncologists likely underestimate the risk of atrial fibrillation when new cancer drugs come to market, they said.

The team came to these conclusions after conducting a meta-analysis of 191 phase 2 or 3 clinical trials that included 26,604 patients. The trials investigated 15 anticancer drugs used as monotherapy.

The meta-analysis showed that the annualized incidence rate of AFib ranged from 0.26 cases per 100 person-years – about the same as placebo – to 4.92 cases, a nearly 20 times’ higher risk.

Rates were the highest for ibrutinib, clofarabine, and ponatinib.

The study was published in JACC: CardioOncology, a journal of the American College of Cardiology.

Actual rates of AFib are probably higher than what they found in this meta-analysis, the authors suspect, because most oncology trials only identify and report severe cases of AFib that require immediate medical attention. Less severe cases can also lead to serious complications, including strokes, but they go unreported, said the investigators, led by Joachim Alexandre, MD, PhD, a member of the cardio-oncology program at the University of Caen Normandie Hospital Center, France.

“These findings suggest a global and systemic underreporting and/or underidentification of cardiotoxicity among cancer clinical trial participants,” and AFib reporting is “particularly affected,” they said.
 

Call for routine monitoring

The root of the problem is the lack of routine rhythm monitoring in cancer trials. This in turn “leads to a significant underestimation of AFib incidence” and rates “markedly lower than those observed among real-life” patients, the authors pointed out.

To address the issue, Dr. Alexandre and his team called for routine cardiac monitoring in trials to capture the true incidence of AFib and to “clearly define which anticancer drugs are significantly associated” with the condition.

Approached for comment, Michael G. Fradley, MD, medical director of cardio-oncology at the University of Pennsylvania, Philadelphia, agreed.

“It’s incredibly important” to “identify the drugs most likely to cause arrhythmias and determine the best prevention and treatment strategies. Unfortunately, systematic evaluation of arrhythmias in cancer clinical trials has often been lacking,” Dr. Fradley told this news organization.

The investigators said the issue is particularly pressing for drugs known to be associated with AFib. For Bruton’s tyrosine kinase inhibitors such as ibrutinib, for instance, they call for standardize AFib detection in trials “not only on 12-lead ECGs” for symptomatic AFib but also with “longer-term ambulatory monitoring or insertable cardiac monitors to detect subclinical AFib.”

Dr. Fradley said there might also be a role for newer wearable technologies that can detect arrhythmias through a skin patch or by other means.
 

Details of the meta-analysis

The investigators pulled the 191 studies they used in their meta-analysis from the ClinicalTrials.gov database.

The trials covered anticancer drugs used as monotherapy up to Sept. 18, 2020. Almost half were randomized trials, but only seven had placebo arms. Trials involving hematologic cancers outnumbered those involving solid tumors.

The 15 drugs examined were dacarbazine, abiraterone, clofarabine, azacitidine, ibrutinib, nilotinib, ponatinib, midostaurin, ipilimumab, aldesleukin, lenalidomide, pomalidomide, rituximab, bortezomib, and docetaxel.

The annualized incidence AFib rates per 100 person-years were 4.92 cases for ibrutinib, 2.38 cases for clofarabine, and 2.35 cases for ponatinib.

The lowest AFib rates were for ipilimumab (0.26 cases), rituximab (0.27), and nilotinib (0.29).

For placebo, the annualized rate was 0.25 cases per 100 person-years.

The team said caution is warranted regarding their estimations for clofarabine and midostaurin (0.65 cases) because no trials were registered after September 2009, when adverse event reporting became mandatory. As a result, estimates may be artificially low.

One of the limits of the study is that it focused on monotherapy in an age when combination treatment is generally the rule for cancer, the authors noted.

No external funding was reported for the study. Dr. Alexandre has received honoraria for presentations and consulting fees from Bayer, BMS, Pfizer, Amgen, and Bioserenity.
 

A version of this article first appeared on Medscape.com.

Atrial fibrillation (AFib) is a known and serious side effect of some cancer treatments, but it is underreported in cancer drug trials, French investigators said in a new report.

As a result, oncologists likely underestimate the risk of atrial fibrillation when new cancer drugs come to market, they said.

The team came to these conclusions after conducting a meta-analysis of 191 phase 2 or 3 clinical trials that included 26,604 patients. The trials investigated 15 anticancer drugs used as monotherapy.

The meta-analysis showed that the annualized incidence rate of AFib ranged from 0.26 cases per 100 person-years – about the same as placebo – to 4.92 cases, a nearly 20 times’ higher risk.

Rates were the highest for ibrutinib, clofarabine, and ponatinib.

The study was published in JACC: CardioOncology, a journal of the American College of Cardiology.

Actual rates of AFib are probably higher than what they found in this meta-analysis, the authors suspect, because most oncology trials only identify and report severe cases of AFib that require immediate medical attention. Less severe cases can also lead to serious complications, including strokes, but they go unreported, said the investigators, led by Joachim Alexandre, MD, PhD, a member of the cardio-oncology program at the University of Caen Normandie Hospital Center, France.

“These findings suggest a global and systemic underreporting and/or underidentification of cardiotoxicity among cancer clinical trial participants,” and AFib reporting is “particularly affected,” they said.
 

Call for routine monitoring

The root of the problem is the lack of routine rhythm monitoring in cancer trials. This in turn “leads to a significant underestimation of AFib incidence” and rates “markedly lower than those observed among real-life” patients, the authors pointed out.

To address the issue, Dr. Alexandre and his team called for routine cardiac monitoring in trials to capture the true incidence of AFib and to “clearly define which anticancer drugs are significantly associated” with the condition.

Approached for comment, Michael G. Fradley, MD, medical director of cardio-oncology at the University of Pennsylvania, Philadelphia, agreed.

“It’s incredibly important” to “identify the drugs most likely to cause arrhythmias and determine the best prevention and treatment strategies. Unfortunately, systematic evaluation of arrhythmias in cancer clinical trials has often been lacking,” Dr. Fradley told this news organization.

The investigators said the issue is particularly pressing for drugs known to be associated with AFib. For Bruton’s tyrosine kinase inhibitors such as ibrutinib, for instance, they call for standardize AFib detection in trials “not only on 12-lead ECGs” for symptomatic AFib but also with “longer-term ambulatory monitoring or insertable cardiac monitors to detect subclinical AFib.”

Dr. Fradley said there might also be a role for newer wearable technologies that can detect arrhythmias through a skin patch or by other means.
 

Details of the meta-analysis

The investigators pulled the 191 studies they used in their meta-analysis from the ClinicalTrials.gov database.

The trials covered anticancer drugs used as monotherapy up to Sept. 18, 2020. Almost half were randomized trials, but only seven had placebo arms. Trials involving hematologic cancers outnumbered those involving solid tumors.

The 15 drugs examined were dacarbazine, abiraterone, clofarabine, azacitidine, ibrutinib, nilotinib, ponatinib, midostaurin, ipilimumab, aldesleukin, lenalidomide, pomalidomide, rituximab, bortezomib, and docetaxel.

The annualized incidence AFib rates per 100 person-years were 4.92 cases for ibrutinib, 2.38 cases for clofarabine, and 2.35 cases for ponatinib.

The lowest AFib rates were for ipilimumab (0.26 cases), rituximab (0.27), and nilotinib (0.29).

For placebo, the annualized rate was 0.25 cases per 100 person-years.

The team said caution is warranted regarding their estimations for clofarabine and midostaurin (0.65 cases) because no trials were registered after September 2009, when adverse event reporting became mandatory. As a result, estimates may be artificially low.

One of the limits of the study is that it focused on monotherapy in an age when combination treatment is generally the rule for cancer, the authors noted.

No external funding was reported for the study. Dr. Alexandre has received honoraria for presentations and consulting fees from Bayer, BMS, Pfizer, Amgen, and Bioserenity.
 

A version of this article first appeared on Medscape.com.

Atrial fibrillation (AFib) is a known and serious side effect of some cancer treatments, but it is underreported in cancer drug trials, French investigators said in a new report.

As a result, oncologists likely underestimate the risk of atrial fibrillation when new cancer drugs come to market, they said.

The team came to these conclusions after conducting a meta-analysis of 191 phase 2 or 3 clinical trials that included 26,604 patients. The trials investigated 15 anticancer drugs used as monotherapy.

The meta-analysis showed that the annualized incidence rate of AFib ranged from 0.26 cases per 100 person-years – about the same as placebo – to 4.92 cases, a nearly 20 times’ higher risk.

Rates were the highest for ibrutinib, clofarabine, and ponatinib.

The study was published in JACC: CardioOncology, a journal of the American College of Cardiology.

Actual rates of AFib are probably higher than what they found in this meta-analysis, the authors suspect, because most oncology trials only identify and report severe cases of AFib that require immediate medical attention. Less severe cases can also lead to serious complications, including strokes, but they go unreported, said the investigators, led by Joachim Alexandre, MD, PhD, a member of the cardio-oncology program at the University of Caen Normandie Hospital Center, France.

“These findings suggest a global and systemic underreporting and/or underidentification of cardiotoxicity among cancer clinical trial participants,” and AFib reporting is “particularly affected,” they said.
 

Call for routine monitoring

The root of the problem is the lack of routine rhythm monitoring in cancer trials. This in turn “leads to a significant underestimation of AFib incidence” and rates “markedly lower than those observed among real-life” patients, the authors pointed out.

To address the issue, Dr. Alexandre and his team called for routine cardiac monitoring in trials to capture the true incidence of AFib and to “clearly define which anticancer drugs are significantly associated” with the condition.

Approached for comment, Michael G. Fradley, MD, medical director of cardio-oncology at the University of Pennsylvania, Philadelphia, agreed.

“It’s incredibly important” to “identify the drugs most likely to cause arrhythmias and determine the best prevention and treatment strategies. Unfortunately, systematic evaluation of arrhythmias in cancer clinical trials has often been lacking,” Dr. Fradley told this news organization.

The investigators said the issue is particularly pressing for drugs known to be associated with AFib. For Bruton’s tyrosine kinase inhibitors such as ibrutinib, for instance, they call for standardize AFib detection in trials “not only on 12-lead ECGs” for symptomatic AFib but also with “longer-term ambulatory monitoring or insertable cardiac monitors to detect subclinical AFib.”

Dr. Fradley said there might also be a role for newer wearable technologies that can detect arrhythmias through a skin patch or by other means.
 

Details of the meta-analysis

The investigators pulled the 191 studies they used in their meta-analysis from the ClinicalTrials.gov database.

The trials covered anticancer drugs used as monotherapy up to Sept. 18, 2020. Almost half were randomized trials, but only seven had placebo arms. Trials involving hematologic cancers outnumbered those involving solid tumors.

The 15 drugs examined were dacarbazine, abiraterone, clofarabine, azacitidine, ibrutinib, nilotinib, ponatinib, midostaurin, ipilimumab, aldesleukin, lenalidomide, pomalidomide, rituximab, bortezomib, and docetaxel.

The annualized incidence AFib rates per 100 person-years were 4.92 cases for ibrutinib, 2.38 cases for clofarabine, and 2.35 cases for ponatinib.

The lowest AFib rates were for ipilimumab (0.26 cases), rituximab (0.27), and nilotinib (0.29).

For placebo, the annualized rate was 0.25 cases per 100 person-years.

The team said caution is warranted regarding their estimations for clofarabine and midostaurin (0.65 cases) because no trials were registered after September 2009, when adverse event reporting became mandatory. As a result, estimates may be artificially low.

One of the limits of the study is that it focused on monotherapy in an age when combination treatment is generally the rule for cancer, the authors noted.

No external funding was reported for the study. Dr. Alexandre has received honoraria for presentations and consulting fees from Bayer, BMS, Pfizer, Amgen, and Bioserenity.
 

A version of this article first appeared on Medscape.com.

Venetoclax (Venclexta) shows promise as salvage therapy for patients with relapsed or refractory hairy cell leukemia (HCL), according to a small study in which five of six patients responded to the drug when used alone or in combination with rituximab.

Venetoclax is already approved for adults with chronic lymphocytic leukemia, small lymphocytic leukemia, and as part of a treatment combination in certain patients with acute myeloid leukemia.

The new findings suggest that the drug could also be a chemotherapy-free treatment option for HCL patients after the failure of multiple prior lines of therapy, including vemurafenib plus rituximab, the investigators wrote in a letter to the editor published in the New England Journal of Medicine.

Treatment options for such patients are limited, they noted.

Enrico Tiacci, MD, of the University of Perugia (Italy), and colleagues decided to explore the use of venetoclax in this patient population after reports of in vitro findings showing a possible benefit.

The investigators administered the drug off-label to six patients who had received vemurafenib plus rituximab as their most recent prior therapy; one was resistant and five relapsed after that therapy, they reported. Venetoclax was delivered in 29-day cycles.

After 6 or 12 cycles, two patients experienced complete remission with minimal residual disease (MRD), and one had partial remission, although each had incomplete platelet recovery.

Adding rituximab at a dose of 375 mg per square meter of body-surface area for three to eight cycles improved the depth of response in a patient who had a previous minor response, further reduced MRD in one who had a complete remission to venetoclax, and led to hematologic remission in one who had no response to venetoclax, they noted.

Progression-free survival ranged from 23 to 53-plus months in all five patients who did not have early progression and was similar or better than PFS seen after vemurafenib plus rituximab.

The main toxic effect of venetoclax was worsening of baseline neutropenia, which was sometimes complicated by infections or febrile neutropenia and was managed by dose reductions and granulocyte colony-stimulating factor.

“Thus, venetoclax with or without rituximab may serve as a safe and effective salvage option after failure of vemurafenib plus rituximab treatment, especially in patients who do not require a rapid recovery of blood count,” they concluded.

The study was supported by grants from Fondazione Associazione Italiana per la Ricerca sul Cancro and the Italian Ministry of Health.

A version of this article first appeared on Medscape.com.

Venetoclax (Venclexta) shows promise as salvage therapy for patients with relapsed or refractory hairy cell leukemia (HCL), according to a small study in which five of six patients responded to the drug when used alone or in combination with rituximab.

Venetoclax is already approved for adults with chronic lymphocytic leukemia, small lymphocytic leukemia, and as part of a treatment combination in certain patients with acute myeloid leukemia.

The new findings suggest that the drug could also be a chemotherapy-free treatment option for HCL patients after the failure of multiple prior lines of therapy, including vemurafenib plus rituximab, the investigators wrote in a letter to the editor published in the New England Journal of Medicine.

Treatment options for such patients are limited, they noted.

Enrico Tiacci, MD, of the University of Perugia (Italy), and colleagues decided to explore the use of venetoclax in this patient population after reports of in vitro findings showing a possible benefit.

The investigators administered the drug off-label to six patients who had received vemurafenib plus rituximab as their most recent prior therapy; one was resistant and five relapsed after that therapy, they reported. Venetoclax was delivered in 29-day cycles.

After 6 or 12 cycles, two patients experienced complete remission with minimal residual disease (MRD), and one had partial remission, although each had incomplete platelet recovery.

Adding rituximab at a dose of 375 mg per square meter of body-surface area for three to eight cycles improved the depth of response in a patient who had a previous minor response, further reduced MRD in one who had a complete remission to venetoclax, and led to hematologic remission in one who had no response to venetoclax, they noted.

Progression-free survival ranged from 23 to 53-plus months in all five patients who did not have early progression and was similar or better than PFS seen after vemurafenib plus rituximab.

The main toxic effect of venetoclax was worsening of baseline neutropenia, which was sometimes complicated by infections or febrile neutropenia and was managed by dose reductions and granulocyte colony-stimulating factor.

“Thus, venetoclax with or without rituximab may serve as a safe and effective salvage option after failure of vemurafenib plus rituximab treatment, especially in patients who do not require a rapid recovery of blood count,” they concluded.

The study was supported by grants from Fondazione Associazione Italiana per la Ricerca sul Cancro and the Italian Ministry of Health.

A version of this article first appeared on Medscape.com.

Venetoclax (Venclexta) shows promise as salvage therapy for patients with relapsed or refractory hairy cell leukemia (HCL), according to a small study in which five of six patients responded to the drug when used alone or in combination with rituximab.

Venetoclax is already approved for adults with chronic lymphocytic leukemia, small lymphocytic leukemia, and as part of a treatment combination in certain patients with acute myeloid leukemia.

The new findings suggest that the drug could also be a chemotherapy-free treatment option for HCL patients after the failure of multiple prior lines of therapy, including vemurafenib plus rituximab, the investigators wrote in a letter to the editor published in the New England Journal of Medicine.

Treatment options for such patients are limited, they noted.

Enrico Tiacci, MD, of the University of Perugia (Italy), and colleagues decided to explore the use of venetoclax in this patient population after reports of in vitro findings showing a possible benefit.

The investigators administered the drug off-label to six patients who had received vemurafenib plus rituximab as their most recent prior therapy; one was resistant and five relapsed after that therapy, they reported. Venetoclax was delivered in 29-day cycles.

After 6 or 12 cycles, two patients experienced complete remission with minimal residual disease (MRD), and one had partial remission, although each had incomplete platelet recovery.

Adding rituximab at a dose of 375 mg per square meter of body-surface area for three to eight cycles improved the depth of response in a patient who had a previous minor response, further reduced MRD in one who had a complete remission to venetoclax, and led to hematologic remission in one who had no response to venetoclax, they noted.

Progression-free survival ranged from 23 to 53-plus months in all five patients who did not have early progression and was similar or better than PFS seen after vemurafenib plus rituximab.

The main toxic effect of venetoclax was worsening of baseline neutropenia, which was sometimes complicated by infections or febrile neutropenia and was managed by dose reductions and granulocyte colony-stimulating factor.

“Thus, venetoclax with or without rituximab may serve as a safe and effective salvage option after failure of vemurafenib plus rituximab treatment, especially in patients who do not require a rapid recovery of blood count,” they concluded.

The study was supported by grants from Fondazione Associazione Italiana per la Ricerca sul Cancro and the Italian Ministry of Health.

A version of this article first appeared on Medscape.com.

Patients with intermediate-risk acute myeloid leukemia (AML) who underwent allogeneic hematopoietic cell transplantation (HCT) after their first complete remission showed improvements in disease-free survival but had similar overall survival rates, compared with patients treated with consolidation chemotherapy alone.

Notably, all patients who relapsed after consolidation chemotherapy were able to receive allogeneic HCT, suggesting that transplantation may be safely delayed in some patients until their first relapse.

“The results of this randomized clinical trial indicate that the probability of survival after [allogeneic] HCT is not superior to that of conventional consolidation chemotherapy” among patients 60 years or younger with intermediate-risk AML, the authors concluded.

However, two experts highlighted several caveats to the study, which suggest the results may not translate to current clinical practice.

The study was published online in JAMA Oncology.

Approximately 50%-70% of patients with AML who receive intensive induction chemotherapy for AML and achieve a first complete remission are referred for post-remission therapy.

While consolidation chemotherapy with high-dose cytarabine has shown a benefit for those with a favorable risk profile, patients considered high-risk with adequate performance status may be candidates for allogeneic HCT.

However, determining the optimal post-remission treatment option for patients who fall into the intermediate-risk category can be more challenging.

To compare outcomes among intermediate-risk patients, researchers from Germany conducted a multicenter trial, enrolling 143 adults aged 60 or younger with intermediate-risk AML who had achieved first complete remission or complete remission with incomplete blood cell count recovery following conventional induction therapy.

The patients, who had a mean age of 48.2 years, were randomly assigned to consolidation treatment with allogeneic HCT (n = 76) or chemotherapy with high-dose cytarabine (n = 67), with the option for salvage HCT in the case of relapse. Overall, 12 patients in the HCT group received one consolidation course of high-dose cytarabine after achieving complete remission to bridge until allogeneic HCT, while all other patients in this group received allogeneic HCT directly after induction therapy.

Overall, disease-free survival at 2 years was significantly higher in the allogeneic HCT group (69%), compared with the consolidation therapy group (40%; P = .001). And the cumulative incidence of relapse at 2 years in the allogeneic HCT group was also lower, at 20%, compared with 58% in the consolidation therapy group (P < .001).

The overall survival data, however, painted a slightly more complex picture. In the intention-to-treat analysis, the probability of survival at 2 years was similar between the allogeneic HCT group (74%, or 56 of 76 patients), compared with consolidation chemotherapy (84%, or 56 of 67 patients; P = .22).

In addition, the rates of nonrelapse mortality at 2 years were higher in the allogeneic HCT group (9%) versus chemotherapy (2%; P = .005).

Although the rate of nonrelapse mortality was higher with allogeneic HCT, the relatively low rate with each treatment strategies was “an important and rewarding finding,” the authors noted. “This achievement is clearly due to the availability of less toxic but still effective conditioning therapies and modern antiviral and antifungal prophylaxis.”

In addition, among the 41 patients who relapsed after consolidation chemotherapy, all received allogeneic HCT, and the authors observed no significant differences between the groups in terms of health-related quality of life measures.
 

Results ‘may not translate to real-life clinical practice’

An important caveat is that the findings do not reflect some key updated strategies currently used in clinical practice, said Diego Adrianzen Herrera, MD, from the University of Vermont’s Larner College of Medicine, Burlington, who was not involved in the study.

“A charitable interpretation of the results is that a clear, large survival benefit of transplant in first complete remission is not apparent, which in turn can inform decision-making in certain circumstances for patients meeting the trial criteria, [including] younger patients with a readily available donor,” he told this news organization.

“However, risk stratification strategies currently used were not followed,” he said.

For instance, molecular risk stratification was not universally used, which may have led the researchers to overrepresent the number of patients considered to have favorable risk disease and “could have skewed the results in favor of the chemotherapy arm,” he explained.

In addition, minimal residual disease surveillance by flow cytometry was not used. Plus, Dr. Herrera added, in practice, not all patients can be salvaged and taken to HCT when in their second complete remission, or even achieve complete remission again.

“Unfortunately, these issues make the clinical significance of these results limited,” he concluded.

Margaret Kasner, MD, who was not associated with the research, agreed that aspects of the study design may not translate to real-life clinical practice, particularly in terms of quality-of-life outcomes.

“Although the [study] showed no difference in quality of life in the patient groups, this is likely due to the patient selection,” Dr. Kasner, of the Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, said in an interview. “Most patients do not allow themselves to be randomized between these two very different strategies, so those who are willing to be randomized may be a different population in terms how their quality of life is affected by relapse.”

The authors acknowledged some of these limitations, adding that the routine use of minimal residual disease monitoring in some patients was only established once the trial was underway, and the number of patients with complete minimal residual disease was therefore limited.

In addition, Dr. Herrera explained that because HCT involves significant disruptions to daily life and extensive follow-up and monitoring, decisions to use the strategy are not taken lightly by clinicians or patients.

“This is a major issue,” he said. “HCT remains a therapeutic option which causes significant apprehension to patients.”

Nevertheless, “in my experience most patients would prefer an upfront strategy if there is a definitive need for transplant,” he added. “I think the main question patients have is whether they absolutely need an HCT and how can we better identify up front who will be in the relapse-free group at 2 years.”

The study received grant funding from the Deutsche Forschungsgemeinschaft. The authors’ disclosures are detailed in the original article. Dr. Herrera and Dr. Kasner report no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Patients with intermediate-risk acute myeloid leukemia (AML) who underwent allogeneic hematopoietic cell transplantation (HCT) after their first complete remission showed improvements in disease-free survival but had similar overall survival rates, compared with patients treated with consolidation chemotherapy alone.

Notably, all patients who relapsed after consolidation chemotherapy were able to receive allogeneic HCT, suggesting that transplantation may be safely delayed in some patients until their first relapse.

“The results of this randomized clinical trial indicate that the probability of survival after [allogeneic] HCT is not superior to that of conventional consolidation chemotherapy” among patients 60 years or younger with intermediate-risk AML, the authors concluded.

However, two experts highlighted several caveats to the study, which suggest the results may not translate to current clinical practice.

The study was published online in JAMA Oncology.

Approximately 50%-70% of patients with AML who receive intensive induction chemotherapy for AML and achieve a first complete remission are referred for post-remission therapy.

While consolidation chemotherapy with high-dose cytarabine has shown a benefit for those with a favorable risk profile, patients considered high-risk with adequate performance status may be candidates for allogeneic HCT.

However, determining the optimal post-remission treatment option for patients who fall into the intermediate-risk category can be more challenging.

To compare outcomes among intermediate-risk patients, researchers from Germany conducted a multicenter trial, enrolling 143 adults aged 60 or younger with intermediate-risk AML who had achieved first complete remission or complete remission with incomplete blood cell count recovery following conventional induction therapy.

The patients, who had a mean age of 48.2 years, were randomly assigned to consolidation treatment with allogeneic HCT (n = 76) or chemotherapy with high-dose cytarabine (n = 67), with the option for salvage HCT in the case of relapse. Overall, 12 patients in the HCT group received one consolidation course of high-dose cytarabine after achieving complete remission to bridge until allogeneic HCT, while all other patients in this group received allogeneic HCT directly after induction therapy.

Overall, disease-free survival at 2 years was significantly higher in the allogeneic HCT group (69%), compared with the consolidation therapy group (40%; P = .001). And the cumulative incidence of relapse at 2 years in the allogeneic HCT group was also lower, at 20%, compared with 58% in the consolidation therapy group (P < .001).

The overall survival data, however, painted a slightly more complex picture. In the intention-to-treat analysis, the probability of survival at 2 years was similar between the allogeneic HCT group (74%, or 56 of 76 patients), compared with consolidation chemotherapy (84%, or 56 of 67 patients; P = .22).

In addition, the rates of nonrelapse mortality at 2 years were higher in the allogeneic HCT group (9%) versus chemotherapy (2%; P = .005).

Although the rate of nonrelapse mortality was higher with allogeneic HCT, the relatively low rate with each treatment strategies was “an important and rewarding finding,” the authors noted. “This achievement is clearly due to the availability of less toxic but still effective conditioning therapies and modern antiviral and antifungal prophylaxis.”

In addition, among the 41 patients who relapsed after consolidation chemotherapy, all received allogeneic HCT, and the authors observed no significant differences between the groups in terms of health-related quality of life measures.
 

Results ‘may not translate to real-life clinical practice’

An important caveat is that the findings do not reflect some key updated strategies currently used in clinical practice, said Diego Adrianzen Herrera, MD, from the University of Vermont’s Larner College of Medicine, Burlington, who was not involved in the study.

“A charitable interpretation of the results is that a clear, large survival benefit of transplant in first complete remission is not apparent, which in turn can inform decision-making in certain circumstances for patients meeting the trial criteria, [including] younger patients with a readily available donor,” he told this news organization.

“However, risk stratification strategies currently used were not followed,” he said.

For instance, molecular risk stratification was not universally used, which may have led the researchers to overrepresent the number of patients considered to have favorable risk disease and “could have skewed the results in favor of the chemotherapy arm,” he explained.

In addition, minimal residual disease surveillance by flow cytometry was not used. Plus, Dr. Herrera added, in practice, not all patients can be salvaged and taken to HCT when in their second complete remission, or even achieve complete remission again.

“Unfortunately, these issues make the clinical significance of these results limited,” he concluded.

Margaret Kasner, MD, who was not associated with the research, agreed that aspects of the study design may not translate to real-life clinical practice, particularly in terms of quality-of-life outcomes.

“Although the [study] showed no difference in quality of life in the patient groups, this is likely due to the patient selection,” Dr. Kasner, of the Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, said in an interview. “Most patients do not allow themselves to be randomized between these two very different strategies, so those who are willing to be randomized may be a different population in terms how their quality of life is affected by relapse.”

The authors acknowledged some of these limitations, adding that the routine use of minimal residual disease monitoring in some patients was only established once the trial was underway, and the number of patients with complete minimal residual disease was therefore limited.

In addition, Dr. Herrera explained that because HCT involves significant disruptions to daily life and extensive follow-up and monitoring, decisions to use the strategy are not taken lightly by clinicians or patients.

“This is a major issue,” he said. “HCT remains a therapeutic option which causes significant apprehension to patients.”

Nevertheless, “in my experience most patients would prefer an upfront strategy if there is a definitive need for transplant,” he added. “I think the main question patients have is whether they absolutely need an HCT and how can we better identify up front who will be in the relapse-free group at 2 years.”

The study received grant funding from the Deutsche Forschungsgemeinschaft. The authors’ disclosures are detailed in the original article. Dr. Herrera and Dr. Kasner report no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Patients with intermediate-risk acute myeloid leukemia (AML) who underwent allogeneic hematopoietic cell transplantation (HCT) after their first complete remission showed improvements in disease-free survival but had similar overall survival rates, compared with patients treated with consolidation chemotherapy alone.

Notably, all patients who relapsed after consolidation chemotherapy were able to receive allogeneic HCT, suggesting that transplantation may be safely delayed in some patients until their first relapse.

“The results of this randomized clinical trial indicate that the probability of survival after [allogeneic] HCT is not superior to that of conventional consolidation chemotherapy” among patients 60 years or younger with intermediate-risk AML, the authors concluded.

However, two experts highlighted several caveats to the study, which suggest the results may not translate to current clinical practice.

The study was published online in JAMA Oncology.

Approximately 50%-70% of patients with AML who receive intensive induction chemotherapy for AML and achieve a first complete remission are referred for post-remission therapy.

While consolidation chemotherapy with high-dose cytarabine has shown a benefit for those with a favorable risk profile, patients considered high-risk with adequate performance status may be candidates for allogeneic HCT.

However, determining the optimal post-remission treatment option for patients who fall into the intermediate-risk category can be more challenging.

To compare outcomes among intermediate-risk patients, researchers from Germany conducted a multicenter trial, enrolling 143 adults aged 60 or younger with intermediate-risk AML who had achieved first complete remission or complete remission with incomplete blood cell count recovery following conventional induction therapy.

The patients, who had a mean age of 48.2 years, were randomly assigned to consolidation treatment with allogeneic HCT (n = 76) or chemotherapy with high-dose cytarabine (n = 67), with the option for salvage HCT in the case of relapse. Overall, 12 patients in the HCT group received one consolidation course of high-dose cytarabine after achieving complete remission to bridge until allogeneic HCT, while all other patients in this group received allogeneic HCT directly after induction therapy.

Overall, disease-free survival at 2 years was significantly higher in the allogeneic HCT group (69%), compared with the consolidation therapy group (40%; P = .001). And the cumulative incidence of relapse at 2 years in the allogeneic HCT group was also lower, at 20%, compared with 58% in the consolidation therapy group (P < .001).

The overall survival data, however, painted a slightly more complex picture. In the intention-to-treat analysis, the probability of survival at 2 years was similar between the allogeneic HCT group (74%, or 56 of 76 patients), compared with consolidation chemotherapy (84%, or 56 of 67 patients; P = .22).

In addition, the rates of nonrelapse mortality at 2 years were higher in the allogeneic HCT group (9%) versus chemotherapy (2%; P = .005).

Although the rate of nonrelapse mortality was higher with allogeneic HCT, the relatively low rate with each treatment strategies was “an important and rewarding finding,” the authors noted. “This achievement is clearly due to the availability of less toxic but still effective conditioning therapies and modern antiviral and antifungal prophylaxis.”

In addition, among the 41 patients who relapsed after consolidation chemotherapy, all received allogeneic HCT, and the authors observed no significant differences between the groups in terms of health-related quality of life measures.
 

Results ‘may not translate to real-life clinical practice’

An important caveat is that the findings do not reflect some key updated strategies currently used in clinical practice, said Diego Adrianzen Herrera, MD, from the University of Vermont’s Larner College of Medicine, Burlington, who was not involved in the study.

“A charitable interpretation of the results is that a clear, large survival benefit of transplant in first complete remission is not apparent, which in turn can inform decision-making in certain circumstances for patients meeting the trial criteria, [including] younger patients with a readily available donor,” he told this news organization.

“However, risk stratification strategies currently used were not followed,” he said.

For instance, molecular risk stratification was not universally used, which may have led the researchers to overrepresent the number of patients considered to have favorable risk disease and “could have skewed the results in favor of the chemotherapy arm,” he explained.

In addition, minimal residual disease surveillance by flow cytometry was not used. Plus, Dr. Herrera added, in practice, not all patients can be salvaged and taken to HCT when in their second complete remission, or even achieve complete remission again.

“Unfortunately, these issues make the clinical significance of these results limited,” he concluded.

Margaret Kasner, MD, who was not associated with the research, agreed that aspects of the study design may not translate to real-life clinical practice, particularly in terms of quality-of-life outcomes.

“Although the [study] showed no difference in quality of life in the patient groups, this is likely due to the patient selection,” Dr. Kasner, of the Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, said in an interview. “Most patients do not allow themselves to be randomized between these two very different strategies, so those who are willing to be randomized may be a different population in terms how their quality of life is affected by relapse.”

The authors acknowledged some of these limitations, adding that the routine use of minimal residual disease monitoring in some patients was only established once the trial was underway, and the number of patients with complete minimal residual disease was therefore limited.

In addition, Dr. Herrera explained that because HCT involves significant disruptions to daily life and extensive follow-up and monitoring, decisions to use the strategy are not taken lightly by clinicians or patients.

“This is a major issue,” he said. “HCT remains a therapeutic option which causes significant apprehension to patients.”

Nevertheless, “in my experience most patients would prefer an upfront strategy if there is a definitive need for transplant,” he added. “I think the main question patients have is whether they absolutely need an HCT and how can we better identify up front who will be in the relapse-free group at 2 years.”

The study received grant funding from the Deutsche Forschungsgemeinschaft. The authors’ disclosures are detailed in the original article. Dr. Herrera and Dr. Kasner report no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

NEW ORLEANS – Investigators confessed to being “astonished” by results of a randomized trial showing that patients with acute myeloid leukemia (AML) who have a poor response after induction therapy do just as well proceeding straight to immediate allogeneic transplant as they would if they had received an intensive salvage induction regimen to get them into remission before transplant.

The results come from the phase 3 ASAP Trial and were presented at the annual meeting of the American Society of Hematology.

“We selected this to be in the plenary because it completely changes how we’ve traditionally thought about acute myeloid leukemia,” commented press briefing moderator Mikkael A. Sekeres, MD, from the University of Miami, who also serves as chair of the ASH Committee on Communications.

“When we have a patient who has relapsed or refractory AML, that person is in a very, very difficult situation, and the mortality among those sort of patients is incredibly high,” Dr. Sekeres commented. “So traditionally we’ve given them very high doses of chemotherapy to try to reduce the tumor burden – at least that’s been the theory – to then get them successfully to a transplant.”

This new finding “completely upends that, if these results hold,” he said. The clinical implication is that “we no longer have to hospitalize these patients and give them very aggressive chemotherapy ... [and] we don’t introduce all the morbidity from giving them very high dose chemotherapy, which can actually prevent a transplant from happening if they get sick enough, and we can get them to a transplant quicker.”

The ASAP trial was conducted in patients with an unfavorable risk AML who either had a poor response to first induction therapy or a relapse after first induction therapy.

They were randomly assigned to either a remission-induction strategy aiming for a better response prior to an allogeneic hematopoietic stem cell transplant (alloHCT), or a disease-control strategy consisting primarily of watchful waiting with low-dose cytarabine and single doses of mitoxantrone as needed, followed by sequential conditioning and alloHCT.

The results after 4 years of follow-up showed no differences in either leukemia-free survival or overall survival between patients who underwent additional chemotherapy with the remission-induction strategy and those who went straight to transplant, reported Johannes Schetelig, MD, MSc, from the Clinical Trials Unit at DKMS, Dresden, Germany.

“We expected non-inferiority – this was what we tested, and of course this was based on an assumption that we could get close or even somewhat better with respect to the primary endpoint, disease-free survival, after transplantation,” he said.

“What we did not expect is that the early success, [complete response] on day 56 after transplantation, also translates into equal long-term benefit, so this is what I was really astonished about,” Dr. Schetelig said at a press briefing prior to his presentation.
 

Less intensive approach

Dr. Schetelig explained that the rationale for the study was previous work by his group and others showing that alloHCT in patients with residual aplasia after first induction is feasible, with favorable outcomes, compared with standard of care. Additionally, the impetus for the research was evidence that sequential conditioning based on high-dose cytarabine or melphalan plus reduced-intensity conditioning and alloHCT resulted in long-term control for relapsed or refractory AML.

Dr. Schetelig also gave details of the two treatment arms of the ASAP trial. The remission-inducing arm consisted of cytarabine (3 g/m² for younger patients or 1 g/m² for patients over age 60) twice daily on days 1-3 plus 10 mitoxantrone mg/m² on days 3-5 and subsequent alloHCT. In the other group – disease control prior to sequential conditioning and alloHCT – watchful waiting was recommended, but low-dose cytarabine (LDAC) and single doses of mitoxantrone were permitted for disease control.

Although, as Dr. Schetelig noted, the statistical goal of the study was to show non-inferiority of the disease control arm, this less intensive strategy exceeded expectations for meeting the primary endpoint of disease-free survival (DFS; a maintained complete response) by day 56 after alloHCT.

In an intention-to-treat and per-protocol analysis, the respective rates of DFS at 56 days in the disease control group were 83.5% and 84.1%. In comparison, the respective rates in the remission-induction group were 81% and 81.3%.

Further, after a median follow-up from randomization of 37 months, there were no differences in either leukemia-free survival or overall survival out to 4 years after DFS at day 56.

The disease-control strategy was also associated with significantly fewer adverse events grade 3 or greater (23% vs. 64%, P < .001), and fewer days in hospital prior to transplant (mean 19 vs. 42, P < .001). There were no significant differences between the trial arms in either deaths within 28 days of randomization or time to discharge from hospital (28 days in each arm).

“These data support sequential conditioning and alloHCT without prior remission-induction chemotherapy whenever a stem cell donor is readily available,” the researchers concluded.

“These results underline the importance of facilitating alloHCT as [the] most effective anti-leukemic therapy in patients with [relapsed or refractory] AML and stress the need for starting donor search at diagnosis,” they added.

The study was sponsored by DKMS gemeinnützige GmbH. Dr. Schetelig disclosed honoraria from BeiGene, BMS, Janssen, AstraZeneca, AbbVie, and DKMS. Dr. Sekkeres reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – Investigators confessed to being “astonished” by results of a randomized trial showing that patients with acute myeloid leukemia (AML) who have a poor response after induction therapy do just as well proceeding straight to immediate allogeneic transplant as they would if they had received an intensive salvage induction regimen to get them into remission before transplant.

The results come from the phase 3 ASAP Trial and were presented at the annual meeting of the American Society of Hematology.

“We selected this to be in the plenary because it completely changes how we’ve traditionally thought about acute myeloid leukemia,” commented press briefing moderator Mikkael A. Sekeres, MD, from the University of Miami, who also serves as chair of the ASH Committee on Communications.

“When we have a patient who has relapsed or refractory AML, that person is in a very, very difficult situation, and the mortality among those sort of patients is incredibly high,” Dr. Sekeres commented. “So traditionally we’ve given them very high doses of chemotherapy to try to reduce the tumor burden – at least that’s been the theory – to then get them successfully to a transplant.”

This new finding “completely upends that, if these results hold,” he said. The clinical implication is that “we no longer have to hospitalize these patients and give them very aggressive chemotherapy ... [and] we don’t introduce all the morbidity from giving them very high dose chemotherapy, which can actually prevent a transplant from happening if they get sick enough, and we can get them to a transplant quicker.”

The ASAP trial was conducted in patients with an unfavorable risk AML who either had a poor response to first induction therapy or a relapse after first induction therapy.

They were randomly assigned to either a remission-induction strategy aiming for a better response prior to an allogeneic hematopoietic stem cell transplant (alloHCT), or a disease-control strategy consisting primarily of watchful waiting with low-dose cytarabine and single doses of mitoxantrone as needed, followed by sequential conditioning and alloHCT.

The results after 4 years of follow-up showed no differences in either leukemia-free survival or overall survival between patients who underwent additional chemotherapy with the remission-induction strategy and those who went straight to transplant, reported Johannes Schetelig, MD, MSc, from the Clinical Trials Unit at DKMS, Dresden, Germany.

“We expected non-inferiority – this was what we tested, and of course this was based on an assumption that we could get close or even somewhat better with respect to the primary endpoint, disease-free survival, after transplantation,” he said.

“What we did not expect is that the early success, [complete response] on day 56 after transplantation, also translates into equal long-term benefit, so this is what I was really astonished about,” Dr. Schetelig said at a press briefing prior to his presentation.
 

Less intensive approach

Dr. Schetelig explained that the rationale for the study was previous work by his group and others showing that alloHCT in patients with residual aplasia after first induction is feasible, with favorable outcomes, compared with standard of care. Additionally, the impetus for the research was evidence that sequential conditioning based on high-dose cytarabine or melphalan plus reduced-intensity conditioning and alloHCT resulted in long-term control for relapsed or refractory AML.

Dr. Schetelig also gave details of the two treatment arms of the ASAP trial. The remission-inducing arm consisted of cytarabine (3 g/m² for younger patients or 1 g/m² for patients over age 60) twice daily on days 1-3 plus 10 mitoxantrone mg/m² on days 3-5 and subsequent alloHCT. In the other group – disease control prior to sequential conditioning and alloHCT – watchful waiting was recommended, but low-dose cytarabine (LDAC) and single doses of mitoxantrone were permitted for disease control.

Although, as Dr. Schetelig noted, the statistical goal of the study was to show non-inferiority of the disease control arm, this less intensive strategy exceeded expectations for meeting the primary endpoint of disease-free survival (DFS; a maintained complete response) by day 56 after alloHCT.

In an intention-to-treat and per-protocol analysis, the respective rates of DFS at 56 days in the disease control group were 83.5% and 84.1%. In comparison, the respective rates in the remission-induction group were 81% and 81.3%.

Further, after a median follow-up from randomization of 37 months, there were no differences in either leukemia-free survival or overall survival out to 4 years after DFS at day 56.

The disease-control strategy was also associated with significantly fewer adverse events grade 3 or greater (23% vs. 64%, P < .001), and fewer days in hospital prior to transplant (mean 19 vs. 42, P < .001). There were no significant differences between the trial arms in either deaths within 28 days of randomization or time to discharge from hospital (28 days in each arm).

“These data support sequential conditioning and alloHCT without prior remission-induction chemotherapy whenever a stem cell donor is readily available,” the researchers concluded.

“These results underline the importance of facilitating alloHCT as [the] most effective anti-leukemic therapy in patients with [relapsed or refractory] AML and stress the need for starting donor search at diagnosis,” they added.

The study was sponsored by DKMS gemeinnützige GmbH. Dr. Schetelig disclosed honoraria from BeiGene, BMS, Janssen, AstraZeneca, AbbVie, and DKMS. Dr. Sekkeres reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – Investigators confessed to being “astonished” by results of a randomized trial showing that patients with acute myeloid leukemia (AML) who have a poor response after induction therapy do just as well proceeding straight to immediate allogeneic transplant as they would if they had received an intensive salvage induction regimen to get them into remission before transplant.

The results come from the phase 3 ASAP Trial and were presented at the annual meeting of the American Society of Hematology.

“We selected this to be in the plenary because it completely changes how we’ve traditionally thought about acute myeloid leukemia,” commented press briefing moderator Mikkael A. Sekeres, MD, from the University of Miami, who also serves as chair of the ASH Committee on Communications.

“When we have a patient who has relapsed or refractory AML, that person is in a very, very difficult situation, and the mortality among those sort of patients is incredibly high,” Dr. Sekeres commented. “So traditionally we’ve given them very high doses of chemotherapy to try to reduce the tumor burden – at least that’s been the theory – to then get them successfully to a transplant.”

This new finding “completely upends that, if these results hold,” he said. The clinical implication is that “we no longer have to hospitalize these patients and give them very aggressive chemotherapy ... [and] we don’t introduce all the morbidity from giving them very high dose chemotherapy, which can actually prevent a transplant from happening if they get sick enough, and we can get them to a transplant quicker.”

The ASAP trial was conducted in patients with an unfavorable risk AML who either had a poor response to first induction therapy or a relapse after first induction therapy.

They were randomly assigned to either a remission-induction strategy aiming for a better response prior to an allogeneic hematopoietic stem cell transplant (alloHCT), or a disease-control strategy consisting primarily of watchful waiting with low-dose cytarabine and single doses of mitoxantrone as needed, followed by sequential conditioning and alloHCT.

The results after 4 years of follow-up showed no differences in either leukemia-free survival or overall survival between patients who underwent additional chemotherapy with the remission-induction strategy and those who went straight to transplant, reported Johannes Schetelig, MD, MSc, from the Clinical Trials Unit at DKMS, Dresden, Germany.

“We expected non-inferiority – this was what we tested, and of course this was based on an assumption that we could get close or even somewhat better with respect to the primary endpoint, disease-free survival, after transplantation,” he said.

“What we did not expect is that the early success, [complete response] on day 56 after transplantation, also translates into equal long-term benefit, so this is what I was really astonished about,” Dr. Schetelig said at a press briefing prior to his presentation.
 

Less intensive approach

Dr. Schetelig explained that the rationale for the study was previous work by his group and others showing that alloHCT in patients with residual aplasia after first induction is feasible, with favorable outcomes, compared with standard of care. Additionally, the impetus for the research was evidence that sequential conditioning based on high-dose cytarabine or melphalan plus reduced-intensity conditioning and alloHCT resulted in long-term control for relapsed or refractory AML.

Dr. Schetelig also gave details of the two treatment arms of the ASAP trial. The remission-inducing arm consisted of cytarabine (3 g/m² for younger patients or 1 g/m² for patients over age 60) twice daily on days 1-3 plus 10 mitoxantrone mg/m² on days 3-5 and subsequent alloHCT. In the other group – disease control prior to sequential conditioning and alloHCT – watchful waiting was recommended, but low-dose cytarabine (LDAC) and single doses of mitoxantrone were permitted for disease control.

Although, as Dr. Schetelig noted, the statistical goal of the study was to show non-inferiority of the disease control arm, this less intensive strategy exceeded expectations for meeting the primary endpoint of disease-free survival (DFS; a maintained complete response) by day 56 after alloHCT.

In an intention-to-treat and per-protocol analysis, the respective rates of DFS at 56 days in the disease control group were 83.5% and 84.1%. In comparison, the respective rates in the remission-induction group were 81% and 81.3%.

Further, after a median follow-up from randomization of 37 months, there were no differences in either leukemia-free survival or overall survival out to 4 years after DFS at day 56.

The disease-control strategy was also associated with significantly fewer adverse events grade 3 or greater (23% vs. 64%, P < .001), and fewer days in hospital prior to transplant (mean 19 vs. 42, P < .001). There were no significant differences between the trial arms in either deaths within 28 days of randomization or time to discharge from hospital (28 days in each arm).

“These data support sequential conditioning and alloHCT without prior remission-induction chemotherapy whenever a stem cell donor is readily available,” the researchers concluded.

“These results underline the importance of facilitating alloHCT as [the] most effective anti-leukemic therapy in patients with [relapsed or refractory] AML and stress the need for starting donor search at diagnosis,” they added.

The study was sponsored by DKMS gemeinnützige GmbH. Dr. Schetelig disclosed honoraria from BeiGene, BMS, Janssen, AstraZeneca, AbbVie, and DKMS. Dr. Sekkeres reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Although acute myeloid leukemia (AML) is on the rise worldwide, and the use of hematopoietic stem cell transplants (HSCT) as a treatment has increased overall, in some countries fewer than 5% of patients are offered this option.

The use of HSCT, the main curative option for AML, “remains unacceptably low,” commented Molly Tokaz, MD, a hematology/oncology fellow at the Fred Hutchinson Cancer Center, Seattle.

She was presenting the findings from a study of worldwide HSCT utilization at the annual meeting of the American Society of Hematology.

Globally, the incidence of AML has increased 16.2% – from 101,867 cases in 2009 to 118,404 in 2016, she noted. This in turn has led to a 54.9% increase in the worldwide use of HSCT for AML, from 9,659 to 14,965 transplants per year over the same period.

North America and Europe have the highest utilization rates of allogeneic HSCT for AML, but even so, fewer than 40% of patients have the procedure, raising a “question of how [well] we are prioritizing the use of HSCT, even in these resource-abundant health systems,” Dr. Tokaz said.

Meanwhile, in Africa, South America, and the Eastern Mediterranean, fewer than 5% of AML patients undergo transplant. Although “resource-constrained regions have the largest growth in HSCT use” in recent years, utilization rates remain abysmally low, “which has profound effects on the expected outcomes for patients in these regions,” she said.

Overall, “patients from lower- and middle-income countries face substantial barriers to accessing stem cell transplantation for AML,” commented Chancellor Donald, MD, a hematologist/oncologist at Tulane University, New Orleans, who moderated the session.

The “stark regional differences” illustrate “inequities in the delivery of stem cell transplants” but also opportunities “to improve access to this potentially curative treatment,” he said.

The goal of the study was to establish a global baseline of HSCT utilization to help focus future expansion efforts aimed at closing regional access gaps. It shows there is much work to be done, Dr. Tokaz said.

An international effort is needed to address the issue, including better data collection, implementation of regional HSCT programs, increased representation of ethnic and racial minorities in international donor registries, and other measures. In many cases, telemedicine can help with sharing cross-border expertise.

In short, what’s needed is a “comprehensive global effort to improve outcomes for patients with AML” worldwide, Dr. Tokaz said.

Timing of transplant is similar across regions, generally coming during the first complete remission, and there’s also been a global shift toward collecting stem cells from peripheral blood.

There has also been a marked shift away from autologous procedures and toward allogeneic transplants, she said.

A key difference between regions, however, is that while more than half of transplants are from unrelated donors in Europe and North America, almost all are from related donors in Africa and the Eastern Mediterranean, with an increasing proportion of haploidentical donors. In addition, the majority of transplants in Asia, the western Pacific, and South America are from related donors.

The use of related donors has implications for HSCT treatment algorithms and outcomes, Dr. Tokaz said.

The estimates of AML incidence were obtained from the 2019 Global Burden of Disease study. Data on HSCT utilization came from the Worldwide Network for Blood and Marrow Transplantation. No funding source was reported. Dr. Tokaz reports no relevant financial relationships, but some co-authors had numerous industry ties. Dr. Donald reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Although acute myeloid leukemia (AML) is on the rise worldwide, and the use of hematopoietic stem cell transplants (HSCT) as a treatment has increased overall, in some countries fewer than 5% of patients are offered this option.

The use of HSCT, the main curative option for AML, “remains unacceptably low,” commented Molly Tokaz, MD, a hematology/oncology fellow at the Fred Hutchinson Cancer Center, Seattle.

She was presenting the findings from a study of worldwide HSCT utilization at the annual meeting of the American Society of Hematology.

Globally, the incidence of AML has increased 16.2% – from 101,867 cases in 2009 to 118,404 in 2016, she noted. This in turn has led to a 54.9% increase in the worldwide use of HSCT for AML, from 9,659 to 14,965 transplants per year over the same period.

North America and Europe have the highest utilization rates of allogeneic HSCT for AML, but even so, fewer than 40% of patients have the procedure, raising a “question of how [well] we are prioritizing the use of HSCT, even in these resource-abundant health systems,” Dr. Tokaz said.

Meanwhile, in Africa, South America, and the Eastern Mediterranean, fewer than 5% of AML patients undergo transplant. Although “resource-constrained regions have the largest growth in HSCT use” in recent years, utilization rates remain abysmally low, “which has profound effects on the expected outcomes for patients in these regions,” she said.

Overall, “patients from lower- and middle-income countries face substantial barriers to accessing stem cell transplantation for AML,” commented Chancellor Donald, MD, a hematologist/oncologist at Tulane University, New Orleans, who moderated the session.

The “stark regional differences” illustrate “inequities in the delivery of stem cell transplants” but also opportunities “to improve access to this potentially curative treatment,” he said.

The goal of the study was to establish a global baseline of HSCT utilization to help focus future expansion efforts aimed at closing regional access gaps. It shows there is much work to be done, Dr. Tokaz said.

An international effort is needed to address the issue, including better data collection, implementation of regional HSCT programs, increased representation of ethnic and racial minorities in international donor registries, and other measures. In many cases, telemedicine can help with sharing cross-border expertise.

In short, what’s needed is a “comprehensive global effort to improve outcomes for patients with AML” worldwide, Dr. Tokaz said.

Timing of transplant is similar across regions, generally coming during the first complete remission, and there’s also been a global shift toward collecting stem cells from peripheral blood.

There has also been a marked shift away from autologous procedures and toward allogeneic transplants, she said.

A key difference between regions, however, is that while more than half of transplants are from unrelated donors in Europe and North America, almost all are from related donors in Africa and the Eastern Mediterranean, with an increasing proportion of haploidentical donors. In addition, the majority of transplants in Asia, the western Pacific, and South America are from related donors.

The use of related donors has implications for HSCT treatment algorithms and outcomes, Dr. Tokaz said.

The estimates of AML incidence were obtained from the 2019 Global Burden of Disease study. Data on HSCT utilization came from the Worldwide Network for Blood and Marrow Transplantation. No funding source was reported. Dr. Tokaz reports no relevant financial relationships, but some co-authors had numerous industry ties. Dr. Donald reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Although acute myeloid leukemia (AML) is on the rise worldwide, and the use of hematopoietic stem cell transplants (HSCT) as a treatment has increased overall, in some countries fewer than 5% of patients are offered this option.

The use of HSCT, the main curative option for AML, “remains unacceptably low,” commented Molly Tokaz, MD, a hematology/oncology fellow at the Fred Hutchinson Cancer Center, Seattle.

She was presenting the findings from a study of worldwide HSCT utilization at the annual meeting of the American Society of Hematology.

Globally, the incidence of AML has increased 16.2% – from 101,867 cases in 2009 to 118,404 in 2016, she noted. This in turn has led to a 54.9% increase in the worldwide use of HSCT for AML, from 9,659 to 14,965 transplants per year over the same period.

North America and Europe have the highest utilization rates of allogeneic HSCT for AML, but even so, fewer than 40% of patients have the procedure, raising a “question of how [well] we are prioritizing the use of HSCT, even in these resource-abundant health systems,” Dr. Tokaz said.

Meanwhile, in Africa, South America, and the Eastern Mediterranean, fewer than 5% of AML patients undergo transplant. Although “resource-constrained regions have the largest growth in HSCT use” in recent years, utilization rates remain abysmally low, “which has profound effects on the expected outcomes for patients in these regions,” she said.

Overall, “patients from lower- and middle-income countries face substantial barriers to accessing stem cell transplantation for AML,” commented Chancellor Donald, MD, a hematologist/oncologist at Tulane University, New Orleans, who moderated the session.

The “stark regional differences” illustrate “inequities in the delivery of stem cell transplants” but also opportunities “to improve access to this potentially curative treatment,” he said.

The goal of the study was to establish a global baseline of HSCT utilization to help focus future expansion efforts aimed at closing regional access gaps. It shows there is much work to be done, Dr. Tokaz said.

An international effort is needed to address the issue, including better data collection, implementation of regional HSCT programs, increased representation of ethnic and racial minorities in international donor registries, and other measures. In many cases, telemedicine can help with sharing cross-border expertise.

In short, what’s needed is a “comprehensive global effort to improve outcomes for patients with AML” worldwide, Dr. Tokaz said.

Timing of transplant is similar across regions, generally coming during the first complete remission, and there’s also been a global shift toward collecting stem cells from peripheral blood.

There has also been a marked shift away from autologous procedures and toward allogeneic transplants, she said.

A key difference between regions, however, is that while more than half of transplants are from unrelated donors in Europe and North America, almost all are from related donors in Africa and the Eastern Mediterranean, with an increasing proportion of haploidentical donors. In addition, the majority of transplants in Asia, the western Pacific, and South America are from related donors.

The use of related donors has implications for HSCT treatment algorithms and outcomes, Dr. Tokaz said.

The estimates of AML incidence were obtained from the 2019 Global Burden of Disease study. Data on HSCT utilization came from the Worldwide Network for Blood and Marrow Transplantation. No funding source was reported. Dr. Tokaz reports no relevant financial relationships, but some co-authors had numerous industry ties. Dr. Donald reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In addition to the latest news in clinical care and drug development, some eyebrow-raising findings that challenge long-held, untested assumptions are promised from the annual meeting of the American Society of Hematology.

The conference starts in New Orleans on Saturday, Dec. 10, , but a sample of what is to come was given last week in a preview media briefing, moderated by Mikkael A. Sekeres, MD, from the University of Miami. Dr. Sekeres, who recently authored a book on the FDA and how it regulates drug approvals, also serves as chair of the ASH Committee on Communications.
 

“Feeding Our Patients Gruel”

Dr. Sekeres expressed particular excitement about a multicenter randomized trial done in Italy. It showed that patients who have neutropenia after a stem cell transplant need not be required to eat a bland diet (Abstract 169).

“We for years have been essentially feeding our patients gruel in the hospital, and these are folks who have to be hospitalized for a stem cell transplant or in my case – I’m a leukemia specialist – for acute leukemia, for 4-6 weeks. The neutropenic diet consists of the blandest food you can imagine, with nothing to really spice it up.”

He noted that a neutropenic diet is so unpalatable that family members often sneak food into patient rooms, and “for years we’ve never seen adverse outcomes in any of those folks who instead of having mashed potatoes and oatmeal ate a corned beef sandwich for dinner.”

Now, the results from this trial “actually give us license to finally allow patients to eat whatever they want,” Dr. Sekeres said.
 

Practice-changing data

ASH experts pointed to two more presentations that are expected to change clinical practice. These include the finding that high-dose methotrexate does not reduce the risk for central nervous system relapse in children with acute lymphoblastic leukemia and lymphoblastic lymphoma (Abstract 214).

Another new study that seems to defy conventional wisdom showed that in adults with relapsed or refractory acute myeloid leukemia, intensive chemotherapy in an effort to achieve remission before a stem cell transplant did not result in better outcomes, compared with sequential conditioning and immediate transplant (Abstract 4).
 

Premature aging in HL survivors

ASH President Jane N. Winter, MD, from Northwestern University, Chicago, who also spoke at the briefing, highlighted a study that followed adult survivors of pediatric Hodgkin lymphoma. This study, from St. Jude Children’s Research Hospital in Memphis and the Wilmot Cancer Institute at the University of Rochester (N.Y), found that these adult survivors are at significantly elevated risk for epigenetic age acceleration accompanied by neurocognitive deficits when compared with controls (Abstract 902).

“This is an area that is very near and dear to my heart,” she said. “Much of my career has focused on reducing the therapy to reduce the long-term consequences of treatments. Pediatricians have been very much wedded to very intensive therapies and tend to incorporate radiation more commonly in their treatment strategies for children than we do in adults.”

Dr. Winter noted that, although clinicians focus primarily on the link between mediastinal radiation and long-term adverse events such as breast cancer, “now we’re shedding a light on the neurocognitive deficits, which I think are underappreciated. Being able to screen for this impact of our treatment, and perhaps then develop strategies to deal with it or prevent it, will have very wide-ranging impact.”
 

Inherited thrombophilia and miscarriage

Cynthia E. Dunbar, MD, chief of the translational stem cell biology branch at the National Heart, Lung, and Blood Institute in Bethesda, Md., who also spoke at the briefing, said that one of the abstracts most important to her practice is a study concerning pregnancy. It showed that low-molecular-weight heparin did not prevent miscarriage in pregnant women with confirmed inherited thrombophilia who had two or more prior pregnancy losses, compared with standard surveillance (Abstract LBA-5).

“This is not my field at all; on the other hand, as a hematologist and a woman, that’s what my emails in the middle of the night and my panicked phone calls are often about. Once somebody has one miscarriage, especially if they feel like they’re already over 30 and the clock is ticking, there’s a huge emphasis and a huge amount of pressure on obstetricians to basically work up for everything, kind of a shotgun [approach],” she said.

Those workups may reveal genetic mutations that are associated with mild elevations in risk for clotting. As a result, some pregnant women are put on anticoagulation therapy, which can cause complications for both pregnancy and delivery. These study findings don’t solve the problem of spontaneous pregnancy loss, but they at least rule out inherited thrombophilia as a preventable cause of miscarriages, Dr. Dunbar said.

Another potentially practice-changing abstract is a study showing that, in younger adults with mantle cell lymphoma, the addition of the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica) to induction therapy and as maintenance with or without autologous stem cell transplant had strong efficacy and acceptable toxicity (Abstract 1).

“The results show that the ibrutinib-containing regimen without transplant is at least as good as the current standard of care with transplant.” Dr. Winter said. “Additional follow-up will be required to show definitively that an autotransplant is unnecessary if ibrutinib is included in this treatment regimen.”

A version of this article first appeared on Medscape.com.

In addition to the latest news in clinical care and drug development, some eyebrow-raising findings that challenge long-held, untested assumptions are promised from the annual meeting of the American Society of Hematology.

The conference starts in New Orleans on Saturday, Dec. 10, , but a sample of what is to come was given last week in a preview media briefing, moderated by Mikkael A. Sekeres, MD, from the University of Miami. Dr. Sekeres, who recently authored a book on the FDA and how it regulates drug approvals, also serves as chair of the ASH Committee on Communications.
 

“Feeding Our Patients Gruel”

Dr. Sekeres expressed particular excitement about a multicenter randomized trial done in Italy. It showed that patients who have neutropenia after a stem cell transplant need not be required to eat a bland diet (Abstract 169).

“We for years have been essentially feeding our patients gruel in the hospital, and these are folks who have to be hospitalized for a stem cell transplant or in my case – I’m a leukemia specialist – for acute leukemia, for 4-6 weeks. The neutropenic diet consists of the blandest food you can imagine, with nothing to really spice it up.”

He noted that a neutropenic diet is so unpalatable that family members often sneak food into patient rooms, and “for years we’ve never seen adverse outcomes in any of those folks who instead of having mashed potatoes and oatmeal ate a corned beef sandwich for dinner.”

Now, the results from this trial “actually give us license to finally allow patients to eat whatever they want,” Dr. Sekeres said.
 

Practice-changing data

ASH experts pointed to two more presentations that are expected to change clinical practice. These include the finding that high-dose methotrexate does not reduce the risk for central nervous system relapse in children with acute lymphoblastic leukemia and lymphoblastic lymphoma (Abstract 214).

Another new study that seems to defy conventional wisdom showed that in adults with relapsed or refractory acute myeloid leukemia, intensive chemotherapy in an effort to achieve remission before a stem cell transplant did not result in better outcomes, compared with sequential conditioning and immediate transplant (Abstract 4).
 

Premature aging in HL survivors

ASH President Jane N. Winter, MD, from Northwestern University, Chicago, who also spoke at the briefing, highlighted a study that followed adult survivors of pediatric Hodgkin lymphoma. This study, from St. Jude Children’s Research Hospital in Memphis and the Wilmot Cancer Institute at the University of Rochester (N.Y), found that these adult survivors are at significantly elevated risk for epigenetic age acceleration accompanied by neurocognitive deficits when compared with controls (Abstract 902).

“This is an area that is very near and dear to my heart,” she said. “Much of my career has focused on reducing the therapy to reduce the long-term consequences of treatments. Pediatricians have been very much wedded to very intensive therapies and tend to incorporate radiation more commonly in their treatment strategies for children than we do in adults.”

Dr. Winter noted that, although clinicians focus primarily on the link between mediastinal radiation and long-term adverse events such as breast cancer, “now we’re shedding a light on the neurocognitive deficits, which I think are underappreciated. Being able to screen for this impact of our treatment, and perhaps then develop strategies to deal with it or prevent it, will have very wide-ranging impact.”
 

Inherited thrombophilia and miscarriage

Cynthia E. Dunbar, MD, chief of the translational stem cell biology branch at the National Heart, Lung, and Blood Institute in Bethesda, Md., who also spoke at the briefing, said that one of the abstracts most important to her practice is a study concerning pregnancy. It showed that low-molecular-weight heparin did not prevent miscarriage in pregnant women with confirmed inherited thrombophilia who had two or more prior pregnancy losses, compared with standard surveillance (Abstract LBA-5).

“This is not my field at all; on the other hand, as a hematologist and a woman, that’s what my emails in the middle of the night and my panicked phone calls are often about. Once somebody has one miscarriage, especially if they feel like they’re already over 30 and the clock is ticking, there’s a huge emphasis and a huge amount of pressure on obstetricians to basically work up for everything, kind of a shotgun [approach],” she said.

Those workups may reveal genetic mutations that are associated with mild elevations in risk for clotting. As a result, some pregnant women are put on anticoagulation therapy, which can cause complications for both pregnancy and delivery. These study findings don’t solve the problem of spontaneous pregnancy loss, but they at least rule out inherited thrombophilia as a preventable cause of miscarriages, Dr. Dunbar said.

Another potentially practice-changing abstract is a study showing that, in younger adults with mantle cell lymphoma, the addition of the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica) to induction therapy and as maintenance with or without autologous stem cell transplant had strong efficacy and acceptable toxicity (Abstract 1).

“The results show that the ibrutinib-containing regimen without transplant is at least as good as the current standard of care with transplant.” Dr. Winter said. “Additional follow-up will be required to show definitively that an autotransplant is unnecessary if ibrutinib is included in this treatment regimen.”

A version of this article first appeared on Medscape.com.

In addition to the latest news in clinical care and drug development, some eyebrow-raising findings that challenge long-held, untested assumptions are promised from the annual meeting of the American Society of Hematology.

The conference starts in New Orleans on Saturday, Dec. 10, , but a sample of what is to come was given last week in a preview media briefing, moderated by Mikkael A. Sekeres, MD, from the University of Miami. Dr. Sekeres, who recently authored a book on the FDA and how it regulates drug approvals, also serves as chair of the ASH Committee on Communications.
 

“Feeding Our Patients Gruel”

Dr. Sekeres expressed particular excitement about a multicenter randomized trial done in Italy. It showed that patients who have neutropenia after a stem cell transplant need not be required to eat a bland diet (Abstract 169).

“We for years have been essentially feeding our patients gruel in the hospital, and these are folks who have to be hospitalized for a stem cell transplant or in my case – I’m a leukemia specialist – for acute leukemia, for 4-6 weeks. The neutropenic diet consists of the blandest food you can imagine, with nothing to really spice it up.”

He noted that a neutropenic diet is so unpalatable that family members often sneak food into patient rooms, and “for years we’ve never seen adverse outcomes in any of those folks who instead of having mashed potatoes and oatmeal ate a corned beef sandwich for dinner.”

Now, the results from this trial “actually give us license to finally allow patients to eat whatever they want,” Dr. Sekeres said.
 

Practice-changing data

ASH experts pointed to two more presentations that are expected to change clinical practice. These include the finding that high-dose methotrexate does not reduce the risk for central nervous system relapse in children with acute lymphoblastic leukemia and lymphoblastic lymphoma (Abstract 214).

Another new study that seems to defy conventional wisdom showed that in adults with relapsed or refractory acute myeloid leukemia, intensive chemotherapy in an effort to achieve remission before a stem cell transplant did not result in better outcomes, compared with sequential conditioning and immediate transplant (Abstract 4).
 

Premature aging in HL survivors

ASH President Jane N. Winter, MD, from Northwestern University, Chicago, who also spoke at the briefing, highlighted a study that followed adult survivors of pediatric Hodgkin lymphoma. This study, from St. Jude Children’s Research Hospital in Memphis and the Wilmot Cancer Institute at the University of Rochester (N.Y), found that these adult survivors are at significantly elevated risk for epigenetic age acceleration accompanied by neurocognitive deficits when compared with controls (Abstract 902).

“This is an area that is very near and dear to my heart,” she said. “Much of my career has focused on reducing the therapy to reduce the long-term consequences of treatments. Pediatricians have been very much wedded to very intensive therapies and tend to incorporate radiation more commonly in their treatment strategies for children than we do in adults.”

Dr. Winter noted that, although clinicians focus primarily on the link between mediastinal radiation and long-term adverse events such as breast cancer, “now we’re shedding a light on the neurocognitive deficits, which I think are underappreciated. Being able to screen for this impact of our treatment, and perhaps then develop strategies to deal with it or prevent it, will have very wide-ranging impact.”
 

Inherited thrombophilia and miscarriage

Cynthia E. Dunbar, MD, chief of the translational stem cell biology branch at the National Heart, Lung, and Blood Institute in Bethesda, Md., who also spoke at the briefing, said that one of the abstracts most important to her practice is a study concerning pregnancy. It showed that low-molecular-weight heparin did not prevent miscarriage in pregnant women with confirmed inherited thrombophilia who had two or more prior pregnancy losses, compared with standard surveillance (Abstract LBA-5).

“This is not my field at all; on the other hand, as a hematologist and a woman, that’s what my emails in the middle of the night and my panicked phone calls are often about. Once somebody has one miscarriage, especially if they feel like they’re already over 30 and the clock is ticking, there’s a huge emphasis and a huge amount of pressure on obstetricians to basically work up for everything, kind of a shotgun [approach],” she said.

Those workups may reveal genetic mutations that are associated with mild elevations in risk for clotting. As a result, some pregnant women are put on anticoagulation therapy, which can cause complications for both pregnancy and delivery. These study findings don’t solve the problem of spontaneous pregnancy loss, but they at least rule out inherited thrombophilia as a preventable cause of miscarriages, Dr. Dunbar said.

Another potentially practice-changing abstract is a study showing that, in younger adults with mantle cell lymphoma, the addition of the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica) to induction therapy and as maintenance with or without autologous stem cell transplant had strong efficacy and acceptable toxicity (Abstract 1).

“The results show that the ibrutinib-containing regimen without transplant is at least as good as the current standard of care with transplant.” Dr. Winter said. “Additional follow-up will be required to show definitively that an autotransplant is unnecessary if ibrutinib is included in this treatment regimen.”

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved olutasidenib (Rezlidhia) for use in certain patients with relapsed or refractory (R/R) acute myeloid leukemia (AML).

Specifically, the drug is approved for use in patients who have R/R AML with a susceptible isocitrate dehydrogenase 1 (IDH1) mutation as detected by an FDA-approved test.

The FDA also approved the Abbott RealTime IDH1 Assay to select patients for treatment.

Olutasidenib is an oral inhibitor of mutated IDH1 that has been designed to bind and inhibit mutated IDH1 to reduce hydroxyglutarate levels and restore cellular differentiation of myeloid cells, says the manufacturer, Rigel.

About half of all patients with AML have relapse after treatment and remission, and about 10%-40% have refractory cases and do not achieve remission even after intensive treatment, the company noted.

“Given the limited treatment options for adult patients with mIDH1 R/R AML, who typically have a poor prognosis, olutasidenib may provide an effective new treatment option with a well-characterized safety profile,” Jorges Cortes, MD, director of the Georgia Cancer Center, Augusta, commented in the company press release. He was an investigator on the phase 2 trial that led to the drug’s approval.

This was Study 2102-HEM-101 (NCT02719574), an open-label, single-arm, multicenter clinical trial that included 147 adult patients with relapsed or refractory AML with an IDH1 mutation confirmed using the Abbott assay.

Olutasidenib was given orally at 150 mg twice daily until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation (performed in 16 patients [11%]). The median treatment duration was 4.7 months (range, 0.1-26 months).

The FDA noted that efficacy was established on the rate of complete remission (CR) plus complete remission with partial hematologic recovery (CRh), the duration of CR+CRh, and the rate of conversion from transfusion dependence to independence.

The CR+CRh rate was 35% (95% confidence interval, 27%-43%), including 32% CR and 2.7% CRh. The median time to CR+CRh was 1.9 months (range, 0.9-5.6 months), and the median duration of CR+CRh was 25.9 months (95% CI, 13.5 months to not reached).

Commenting on these results in the company statement, Dr. Cortes noted that among the patients who responded, more than 90% were experiencing incomplete remission. He added that the “25.9 months median duration of CR+CRh is a clinically meaningful improvement for AML patients and appears to be longer than currently available treatment options.”

The FDA also noted that among the 86 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 29 (34%) became independent of RBC and platelet transfusions during any 56-day postbaseline period.

Of the 61 patients who were independent of both RBC and platelet transfusions at baseline, 39 (64%) remained transfusion-independent during any 56-day post-baseline period.

The most common adverse reactions (≥ 20%) were nausea, fatigue/malaise, arthralgia, constipation, leukocytosis, dyspnea, fever, rash, mucositis, diarrhea, and transaminitis.

The prescribing information contains a boxed warning about the risk for differentiation syndrome, which can be fatal.

Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal, the company explained. Symptoms may include leukocytosis, dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, hypotension, fever, and weight gain.

In the trial, differentiation syndrome was observed in 16% of patients, with grade 3 or 4 occurring in 8% of patients treated and death in 1% of patients. It occurred as early as 1 day and up to 18 months after starting treatment.

In most cases, differentiation syndrome was manageable with dose interruption and corticosteroids, the company said. Of the 25 patients who experienced differentiation syndrome, 19 (76%) recovered after treatment or after dose interruption.

Further details are available in the full prescribing information.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved olutasidenib (Rezlidhia) for use in certain patients with relapsed or refractory (R/R) acute myeloid leukemia (AML).

Specifically, the drug is approved for use in patients who have R/R AML with a susceptible isocitrate dehydrogenase 1 (IDH1) mutation as detected by an FDA-approved test.

The FDA also approved the Abbott RealTime IDH1 Assay to select patients for treatment.

Olutasidenib is an oral inhibitor of mutated IDH1 that has been designed to bind and inhibit mutated IDH1 to reduce hydroxyglutarate levels and restore cellular differentiation of myeloid cells, says the manufacturer, Rigel.

About half of all patients with AML have relapse after treatment and remission, and about 10%-40% have refractory cases and do not achieve remission even after intensive treatment, the company noted.

“Given the limited treatment options for adult patients with mIDH1 R/R AML, who typically have a poor prognosis, olutasidenib may provide an effective new treatment option with a well-characterized safety profile,” Jorges Cortes, MD, director of the Georgia Cancer Center, Augusta, commented in the company press release. He was an investigator on the phase 2 trial that led to the drug’s approval.

This was Study 2102-HEM-101 (NCT02719574), an open-label, single-arm, multicenter clinical trial that included 147 adult patients with relapsed or refractory AML with an IDH1 mutation confirmed using the Abbott assay.

Olutasidenib was given orally at 150 mg twice daily until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation (performed in 16 patients [11%]). The median treatment duration was 4.7 months (range, 0.1-26 months).

The FDA noted that efficacy was established on the rate of complete remission (CR) plus complete remission with partial hematologic recovery (CRh), the duration of CR+CRh, and the rate of conversion from transfusion dependence to independence.

The CR+CRh rate was 35% (95% confidence interval, 27%-43%), including 32% CR and 2.7% CRh. The median time to CR+CRh was 1.9 months (range, 0.9-5.6 months), and the median duration of CR+CRh was 25.9 months (95% CI, 13.5 months to not reached).

Commenting on these results in the company statement, Dr. Cortes noted that among the patients who responded, more than 90% were experiencing incomplete remission. He added that the “25.9 months median duration of CR+CRh is a clinically meaningful improvement for AML patients and appears to be longer than currently available treatment options.”

The FDA also noted that among the 86 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 29 (34%) became independent of RBC and platelet transfusions during any 56-day postbaseline period.

Of the 61 patients who were independent of both RBC and platelet transfusions at baseline, 39 (64%) remained transfusion-independent during any 56-day post-baseline period.

The most common adverse reactions (≥ 20%) were nausea, fatigue/malaise, arthralgia, constipation, leukocytosis, dyspnea, fever, rash, mucositis, diarrhea, and transaminitis.

The prescribing information contains a boxed warning about the risk for differentiation syndrome, which can be fatal.

Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal, the company explained. Symptoms may include leukocytosis, dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, hypotension, fever, and weight gain.

In the trial, differentiation syndrome was observed in 16% of patients, with grade 3 or 4 occurring in 8% of patients treated and death in 1% of patients. It occurred as early as 1 day and up to 18 months after starting treatment.

In most cases, differentiation syndrome was manageable with dose interruption and corticosteroids, the company said. Of the 25 patients who experienced differentiation syndrome, 19 (76%) recovered after treatment or after dose interruption.

Further details are available in the full prescribing information.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved olutasidenib (Rezlidhia) for use in certain patients with relapsed or refractory (R/R) acute myeloid leukemia (AML).

Specifically, the drug is approved for use in patients who have R/R AML with a susceptible isocitrate dehydrogenase 1 (IDH1) mutation as detected by an FDA-approved test.

The FDA also approved the Abbott RealTime IDH1 Assay to select patients for treatment.

Olutasidenib is an oral inhibitor of mutated IDH1 that has been designed to bind and inhibit mutated IDH1 to reduce hydroxyglutarate levels and restore cellular differentiation of myeloid cells, says the manufacturer, Rigel.

About half of all patients with AML have relapse after treatment and remission, and about 10%-40% have refractory cases and do not achieve remission even after intensive treatment, the company noted.

“Given the limited treatment options for adult patients with mIDH1 R/R AML, who typically have a poor prognosis, olutasidenib may provide an effective new treatment option with a well-characterized safety profile,” Jorges Cortes, MD, director of the Georgia Cancer Center, Augusta, commented in the company press release. He was an investigator on the phase 2 trial that led to the drug’s approval.

This was Study 2102-HEM-101 (NCT02719574), an open-label, single-arm, multicenter clinical trial that included 147 adult patients with relapsed or refractory AML with an IDH1 mutation confirmed using the Abbott assay.

Olutasidenib was given orally at 150 mg twice daily until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation (performed in 16 patients [11%]). The median treatment duration was 4.7 months (range, 0.1-26 months).

The FDA noted that efficacy was established on the rate of complete remission (CR) plus complete remission with partial hematologic recovery (CRh), the duration of CR+CRh, and the rate of conversion from transfusion dependence to independence.

The CR+CRh rate was 35% (95% confidence interval, 27%-43%), including 32% CR and 2.7% CRh. The median time to CR+CRh was 1.9 months (range, 0.9-5.6 months), and the median duration of CR+CRh was 25.9 months (95% CI, 13.5 months to not reached).

Commenting on these results in the company statement, Dr. Cortes noted that among the patients who responded, more than 90% were experiencing incomplete remission. He added that the “25.9 months median duration of CR+CRh is a clinically meaningful improvement for AML patients and appears to be longer than currently available treatment options.”

The FDA also noted that among the 86 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 29 (34%) became independent of RBC and platelet transfusions during any 56-day postbaseline period.

Of the 61 patients who were independent of both RBC and platelet transfusions at baseline, 39 (64%) remained transfusion-independent during any 56-day post-baseline period.

The most common adverse reactions (≥ 20%) were nausea, fatigue/malaise, arthralgia, constipation, leukocytosis, dyspnea, fever, rash, mucositis, diarrhea, and transaminitis.

The prescribing information contains a boxed warning about the risk for differentiation syndrome, which can be fatal.

Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal, the company explained. Symptoms may include leukocytosis, dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, hypotension, fever, and weight gain.

In the trial, differentiation syndrome was observed in 16% of patients, with grade 3 or 4 occurring in 8% of patients treated and death in 1% of patients. It occurred as early as 1 day and up to 18 months after starting treatment.

In most cases, differentiation syndrome was manageable with dose interruption and corticosteroids, the company said. Of the 25 patients who experienced differentiation syndrome, 19 (76%) recovered after treatment or after dose interruption.

Further details are available in the full prescribing information.

A version of this article first appeared on Medscape.com.

While great strides have been made in children’s leukemia care during the past 50 years, statistics have remained grim. For acute myeloid leukemia (AML), the most common type, 5-year survival rates were just 69% for children younger than 15 between 2009 and 2015. Patients who do survive past adolescence face high risks of future complications.

Specialists say the challenges hindering more progress include a lack of clinical research, an emphasis on competition over cooperation, and sparse insight into how best to adjust adult leukemia treatments to children. Now, a large clinical trial launched by the Leukemia & Lymphoma Society (LLS) seeks to revolutionize pediatric AML care by testing multiple experimental treatments across the globe. Its goal goes beyond simply boosting survival.

“Our project aims to find better treatments, more targeted treatments, that will leave children with fewer long-term health problems as adults. We want them to not just survive but thrive,” Gwen Nichols, MD, chief medical officer of LLS, said in an interview. “What we’ve had was not working for anybody. So we have to try a different approach.”

The LLS Pediatric Acute Leukemia (PedAL) Master Trial launched in spring of 2022. Seventy-five study locations from Nova Scotia to Hawaii are now recruiting patients up to age 22 with known or suspected relapsed/refractory AML, mixed phenotype acute leukemia, or relapsed acute lymphoblastic leukemia (ALL).

The 5-year trial expects to recruit 960 participants in the United States and Canada. Clinics in Europe, Australia, and New Zealand also are taking part.

“Pediatric oncologists should know that PedAL, for the first time, is providing a cooperative, seamless way to interrogate [the genomics of] a child’s leukemia,” hematologist/oncologist Todd Cooper, DO, section chief of pediatric oncology at Seattle Children’s Cancer and Blood Disorders Center, said in an interview. “It is also providing a seamless and efficient way for children to be assigned to clinical trials that are going to be tailored towards a particular child’s leukemia. This is something that’s never been done.”

In North America, all trial participants with relapsed AML will undergo genetic sequencing for free as part of the screening process. Clinics “can’t always access genomic screening for their patients,” Dr. Nichols said. “We’re providing that even if they don’t participate in any other part of the trial, even if they go and get another available therapy or go on a different trial. We want them to know that this is available, and they will get the results. And if they’re looking for a trial when they get those results, we have trained oncology nurses who will help them navigate and find clinical trials.”

In PedAL itself, one subtrial is now in progress: An open-label phase 3 randomized multicenter analysis of whether the oral leukemia drug venetoclax combined with the intensive infused chemotherapy treatment FLA+GO (fludarabine, high-dose cytarabine, and gemtuzumab ozogamicin) will improve overall survival compared to FLA+GO alone. Ninety-eight subjects are expected to join the 5-year subtrial.

“We expect within the next year to open three or four different subtrials of targeted therapies for specific groups of patients,” E. Anders Kolb, MD, chief of oncology and hematology at Nemours Children’s Health in Delaware and cochair of the PedAL trial, said in an interview. “Over the course of the next few years, we’re going to learn a lot about the natural history of relapsed leukemia – we don’t have a ton of data on that – and then how targeted therapies may alter some of those outcomes.”

Discussions with multiple drugmakers are in progress regarding the potential subtrials, he said.

The PedAL strategy addresses the lack of new drugs for children with AML, Seattle Children’s Dr. Cooper said. One main reason for the gap is that childhood leukemia is much less common than the adult form, he said, so a lot of drug development is geared toward adults. As a result, he said, new drugs “are geared towards adults whose leukemia is not as aggressive. Whereas in children, the acute leukemias, especially AML, are quite aggressive and need therapies that are often more intense.”

In addition, he said, “we have only recently become aware of how AML is biologically much different than in adults.”

In AML, Delaware’s Dr. Kolb explained, “there are many different phenotypes – ways that these cells can look and behave. But we treat them with a single regimen. What I like to tell families is that we’ve got a few tools in our toolbox, but they all happen to be sledgehammers. The key to the challenge in AML is that it is a molecular disease, but we’re treating it with therapies that were developed 40-50 years ago.”

In PedAL, the goal is to figure out the best ways to target therapy for the specific types that patients have. On this front, the genomic screening in the trial is crucial because it will identify which patients express certain targets and allow them to be assigned to appropriate sub-trials, Dr. Coooper said.

What’s next? “LLS has planned for this to be ongoing for the next 5 to 7 years, so that we can get a number of studies up and running,” Dr. Nichols said. “After that, those studies will continue. We will hope that most of them can be self-funded by then.”

As for cost, she noted that the PedAL trial is part of the society’s Dare to Dream Project, formerly known as the Children’s Initiative, which focuses on pediatric blood cancers. The project, with a fundraising goal of $175 million, focuses on research, patient services and survivorship.

”We have a whole range of services, travel assistance, copay programs and educational resources that doctors may want to use as a valid source of information,” she said. ‘When I was in practice, patients were always asking me, ‘Do you have anything I can read or take home to give my son something about his disease?’ LLS has good-quality, patient-level information for patients. We welcome people contacting us or going to our website and taking advantage of that for free.”

Dr. Nichols and Dr. Kolb report no disclosures. Dr. Cooper reports academic funding from LLS.

While great strides have been made in children’s leukemia care during the past 50 years, statistics have remained grim. For acute myeloid leukemia (AML), the most common type, 5-year survival rates were just 69% for children younger than 15 between 2009 and 2015. Patients who do survive past adolescence face high risks of future complications.

Specialists say the challenges hindering more progress include a lack of clinical research, an emphasis on competition over cooperation, and sparse insight into how best to adjust adult leukemia treatments to children. Now, a large clinical trial launched by the Leukemia & Lymphoma Society (LLS) seeks to revolutionize pediatric AML care by testing multiple experimental treatments across the globe. Its goal goes beyond simply boosting survival.

“Our project aims to find better treatments, more targeted treatments, that will leave children with fewer long-term health problems as adults. We want them to not just survive but thrive,” Gwen Nichols, MD, chief medical officer of LLS, said in an interview. “What we’ve had was not working for anybody. So we have to try a different approach.”

The LLS Pediatric Acute Leukemia (PedAL) Master Trial launched in spring of 2022. Seventy-five study locations from Nova Scotia to Hawaii are now recruiting patients up to age 22 with known or suspected relapsed/refractory AML, mixed phenotype acute leukemia, or relapsed acute lymphoblastic leukemia (ALL).

The 5-year trial expects to recruit 960 participants in the United States and Canada. Clinics in Europe, Australia, and New Zealand also are taking part.

“Pediatric oncologists should know that PedAL, for the first time, is providing a cooperative, seamless way to interrogate [the genomics of] a child’s leukemia,” hematologist/oncologist Todd Cooper, DO, section chief of pediatric oncology at Seattle Children’s Cancer and Blood Disorders Center, said in an interview. “It is also providing a seamless and efficient way for children to be assigned to clinical trials that are going to be tailored towards a particular child’s leukemia. This is something that’s never been done.”

In North America, all trial participants with relapsed AML will undergo genetic sequencing for free as part of the screening process. Clinics “can’t always access genomic screening for their patients,” Dr. Nichols said. “We’re providing that even if they don’t participate in any other part of the trial, even if they go and get another available therapy or go on a different trial. We want them to know that this is available, and they will get the results. And if they’re looking for a trial when they get those results, we have trained oncology nurses who will help them navigate and find clinical trials.”

In PedAL itself, one subtrial is now in progress: An open-label phase 3 randomized multicenter analysis of whether the oral leukemia drug venetoclax combined with the intensive infused chemotherapy treatment FLA+GO (fludarabine, high-dose cytarabine, and gemtuzumab ozogamicin) will improve overall survival compared to FLA+GO alone. Ninety-eight subjects are expected to join the 5-year subtrial.

“We expect within the next year to open three or four different subtrials of targeted therapies for specific groups of patients,” E. Anders Kolb, MD, chief of oncology and hematology at Nemours Children’s Health in Delaware and cochair of the PedAL trial, said in an interview. “Over the course of the next few years, we’re going to learn a lot about the natural history of relapsed leukemia – we don’t have a ton of data on that – and then how targeted therapies may alter some of those outcomes.”

Discussions with multiple drugmakers are in progress regarding the potential subtrials, he said.

The PedAL strategy addresses the lack of new drugs for children with AML, Seattle Children’s Dr. Cooper said. One main reason for the gap is that childhood leukemia is much less common than the adult form, he said, so a lot of drug development is geared toward adults. As a result, he said, new drugs “are geared towards adults whose leukemia is not as aggressive. Whereas in children, the acute leukemias, especially AML, are quite aggressive and need therapies that are often more intense.”

In addition, he said, “we have only recently become aware of how AML is biologically much different than in adults.”

In AML, Delaware’s Dr. Kolb explained, “there are many different phenotypes – ways that these cells can look and behave. But we treat them with a single regimen. What I like to tell families is that we’ve got a few tools in our toolbox, but they all happen to be sledgehammers. The key to the challenge in AML is that it is a molecular disease, but we’re treating it with therapies that were developed 40-50 years ago.”

In PedAL, the goal is to figure out the best ways to target therapy for the specific types that patients have. On this front, the genomic screening in the trial is crucial because it will identify which patients express certain targets and allow them to be assigned to appropriate sub-trials, Dr. Coooper said.

What’s next? “LLS has planned for this to be ongoing for the next 5 to 7 years, so that we can get a number of studies up and running,” Dr. Nichols said. “After that, those studies will continue. We will hope that most of them can be self-funded by then.”

As for cost, she noted that the PedAL trial is part of the society’s Dare to Dream Project, formerly known as the Children’s Initiative, which focuses on pediatric blood cancers. The project, with a fundraising goal of $175 million, focuses on research, patient services and survivorship.

”We have a whole range of services, travel assistance, copay programs and educational resources that doctors may want to use as a valid source of information,” she said. ‘When I was in practice, patients were always asking me, ‘Do you have anything I can read or take home to give my son something about his disease?’ LLS has good-quality, patient-level information for patients. We welcome people contacting us or going to our website and taking advantage of that for free.”

Dr. Nichols and Dr. Kolb report no disclosures. Dr. Cooper reports academic funding from LLS.

While great strides have been made in children’s leukemia care during the past 50 years, statistics have remained grim. For acute myeloid leukemia (AML), the most common type, 5-year survival rates were just 69% for children younger than 15 between 2009 and 2015. Patients who do survive past adolescence face high risks of future complications.

Specialists say the challenges hindering more progress include a lack of clinical research, an emphasis on competition over cooperation, and sparse insight into how best to adjust adult leukemia treatments to children. Now, a large clinical trial launched by the Leukemia & Lymphoma Society (LLS) seeks to revolutionize pediatric AML care by testing multiple experimental treatments across the globe. Its goal goes beyond simply boosting survival.

“Our project aims to find better treatments, more targeted treatments, that will leave children with fewer long-term health problems as adults. We want them to not just survive but thrive,” Gwen Nichols, MD, chief medical officer of LLS, said in an interview. “What we’ve had was not working for anybody. So we have to try a different approach.”

The LLS Pediatric Acute Leukemia (PedAL) Master Trial launched in spring of 2022. Seventy-five study locations from Nova Scotia to Hawaii are now recruiting patients up to age 22 with known or suspected relapsed/refractory AML, mixed phenotype acute leukemia, or relapsed acute lymphoblastic leukemia (ALL).

The 5-year trial expects to recruit 960 participants in the United States and Canada. Clinics in Europe, Australia, and New Zealand also are taking part.

“Pediatric oncologists should know that PedAL, for the first time, is providing a cooperative, seamless way to interrogate [the genomics of] a child’s leukemia,” hematologist/oncologist Todd Cooper, DO, section chief of pediatric oncology at Seattle Children’s Cancer and Blood Disorders Center, said in an interview. “It is also providing a seamless and efficient way for children to be assigned to clinical trials that are going to be tailored towards a particular child’s leukemia. This is something that’s never been done.”

In North America, all trial participants with relapsed AML will undergo genetic sequencing for free as part of the screening process. Clinics “can’t always access genomic screening for their patients,” Dr. Nichols said. “We’re providing that even if they don’t participate in any other part of the trial, even if they go and get another available therapy or go on a different trial. We want them to know that this is available, and they will get the results. And if they’re looking for a trial when they get those results, we have trained oncology nurses who will help them navigate and find clinical trials.”

In PedAL itself, one subtrial is now in progress: An open-label phase 3 randomized multicenter analysis of whether the oral leukemia drug venetoclax combined with the intensive infused chemotherapy treatment FLA+GO (fludarabine, high-dose cytarabine, and gemtuzumab ozogamicin) will improve overall survival compared to FLA+GO alone. Ninety-eight subjects are expected to join the 5-year subtrial.

“We expect within the next year to open three or four different subtrials of targeted therapies for specific groups of patients,” E. Anders Kolb, MD, chief of oncology and hematology at Nemours Children’s Health in Delaware and cochair of the PedAL trial, said in an interview. “Over the course of the next few years, we’re going to learn a lot about the natural history of relapsed leukemia – we don’t have a ton of data on that – and then how targeted therapies may alter some of those outcomes.”

Discussions with multiple drugmakers are in progress regarding the potential subtrials, he said.

The PedAL strategy addresses the lack of new drugs for children with AML, Seattle Children’s Dr. Cooper said. One main reason for the gap is that childhood leukemia is much less common than the adult form, he said, so a lot of drug development is geared toward adults. As a result, he said, new drugs “are geared towards adults whose leukemia is not as aggressive. Whereas in children, the acute leukemias, especially AML, are quite aggressive and need therapies that are often more intense.”

In addition, he said, “we have only recently become aware of how AML is biologically much different than in adults.”

In AML, Delaware’s Dr. Kolb explained, “there are many different phenotypes – ways that these cells can look and behave. But we treat them with a single regimen. What I like to tell families is that we’ve got a few tools in our toolbox, but they all happen to be sledgehammers. The key to the challenge in AML is that it is a molecular disease, but we’re treating it with therapies that were developed 40-50 years ago.”

In PedAL, the goal is to figure out the best ways to target therapy for the specific types that patients have. On this front, the genomic screening in the trial is crucial because it will identify which patients express certain targets and allow them to be assigned to appropriate sub-trials, Dr. Coooper said.

What’s next? “LLS has planned for this to be ongoing for the next 5 to 7 years, so that we can get a number of studies up and running,” Dr. Nichols said. “After that, those studies will continue. We will hope that most of them can be self-funded by then.”

As for cost, she noted that the PedAL trial is part of the society’s Dare to Dream Project, formerly known as the Children’s Initiative, which focuses on pediatric blood cancers. The project, with a fundraising goal of $175 million, focuses on research, patient services and survivorship.

”We have a whole range of services, travel assistance, copay programs and educational resources that doctors may want to use as a valid source of information,” she said. ‘When I was in practice, patients were always asking me, ‘Do you have anything I can read or take home to give my son something about his disease?’ LLS has good-quality, patient-level information for patients. We welcome people contacting us or going to our website and taking advantage of that for free.”

Dr. Nichols and Dr. Kolb report no disclosures. Dr. Cooper reports academic funding from LLS.

Adding venetoclax (Venclexta) to a gilteritinib (Xospata) regimen appeared to improve outcomes in refractory/relapsed FLT3-mutated acute myeloid leukemia (AML), a new industry-funded phase 1b study reported.

“The combination of venetoclax and gilteritinib is a highly active and tolerable oral combination regimen that potentially improves response frequency and depth over existing standards in a high-risk, mutation-defined group of patients with AML,” wrote the authors of the study, which appeared in the Journal of Clinical Oncology.

Outcomes in AML are poor. As the study notes, most patients relapse and face a median overall survival of 4-7 months even with standard chemotherapy. Gilteritinib, a selective oral FLT3 inhibitor, is Food and Drug Administration–approved for the 30% of relapsed/refractory patients with AML who have FLT3 mutations.

“The general sentiment is that, although some patients have great benefit from gilteritinib monotherapy, there is room to improve the quality, frequency, and duration of responses with combinations,” said hematologist Andrew Brunner, MD, of Massachusetts General Hospital in Boston, in an interview. He was not involved with the study research.

For the new open-label, dose-escalation/dose-expansion study, led by hematologist Naval Daver, MD, of the University of Texas MD Anderson Cancer Center, Houston, researchers enrolled 61 patients (56 with FLT3 mutations) from 2018 to 2020. The median age was 63 years (range 21-85).

The subjects were assigned to get a recommended phase 2 dose of 400 mg venetoclax once daily and 120 mg gilteritinib once daily.

Over a median follow-up of 17.5 months, the median remission time was 4.9 months (95% confidence interval, 3.4-6.6), and the patients with FLT3 mutations survived a median of 10 months.

“The combination of venetoclax and gilteritinib was tolerable at standard doses of each drug, generated remarkably high response rates, and markedly reduced FLT3-internal tandem duplications mutation burden. … Early mortality was similar to gilteritinib monotherapy,” the authors wrote.

Eighty percent of patients experienced cytopenias, and “adverse events prompted venetoclax and gilteritinib dose interruptions in 51% and 48%, respectively.”

About 60% of patients who went on to receive allogeneic hematopoietic stem cell transplantation were alive at the end of follow-up, “suggesting that VenGilt [the combo treatment] could be an effective bridge to transplant in young/fit patients with relapsed FLT3mut AML,” the researchers wrote.

All patients withdrew from the study by November 2021 for several reasons such as death (n=42), adverse events (n=10), and disease progression (29); some had multiple reasons.

Dr. Brunner said the study is “an important step toward evaluating a new potential regimen.”

The remission duration, FLT3 molecular response, and median overall survival “seem quite encouraging for a severe disease like AML in relapse,” he said. However, he added that the drug combo “would need to be evaluated in a randomized and, ideally, placebo-controlled setting to know if this is a significant improvement.”

He also highlighted the high number of severe cyptopenias with associated complications such as death. “Whether this is acceptable depends on the patient and circumstances,” he said. “But it does suggest that this regimen would potentially be for more robust patients, particularly since the group that did best were those who went to transplant later.”

Pending more research, Dr. Brunner said, “I am not sure I would use [the combination treatment] over gilteritinib monotherapy, for instance. But there may be settings where no other options are available, and this could be considered, particularly if a transplant option is a next step.”

The study was funded by AbbVie, Genentech, and Astellas. The study authors report multiple disclosures; some are employed by Astellas, AbbVie, and Genentech/Roche.

Dr. Bronner reports running clinical trials, advisory board service and/or consultation for Acceleron, Agios, Abbvie, BMS/Celgene, Keros Therapeutics, Novartis, Takeda, GSK, AstraZeneca, Janssen, and Gilead.

Adding venetoclax (Venclexta) to a gilteritinib (Xospata) regimen appeared to improve outcomes in refractory/relapsed FLT3-mutated acute myeloid leukemia (AML), a new industry-funded phase 1b study reported.

“The combination of venetoclax and gilteritinib is a highly active and tolerable oral combination regimen that potentially improves response frequency and depth over existing standards in a high-risk, mutation-defined group of patients with AML,” wrote the authors of the study, which appeared in the Journal of Clinical Oncology.

Outcomes in AML are poor. As the study notes, most patients relapse and face a median overall survival of 4-7 months even with standard chemotherapy. Gilteritinib, a selective oral FLT3 inhibitor, is Food and Drug Administration–approved for the 30% of relapsed/refractory patients with AML who have FLT3 mutations.

“The general sentiment is that, although some patients have great benefit from gilteritinib monotherapy, there is room to improve the quality, frequency, and duration of responses with combinations,” said hematologist Andrew Brunner, MD, of Massachusetts General Hospital in Boston, in an interview. He was not involved with the study research.

For the new open-label, dose-escalation/dose-expansion study, led by hematologist Naval Daver, MD, of the University of Texas MD Anderson Cancer Center, Houston, researchers enrolled 61 patients (56 with FLT3 mutations) from 2018 to 2020. The median age was 63 years (range 21-85).

The subjects were assigned to get a recommended phase 2 dose of 400 mg venetoclax once daily and 120 mg gilteritinib once daily.

Over a median follow-up of 17.5 months, the median remission time was 4.9 months (95% confidence interval, 3.4-6.6), and the patients with FLT3 mutations survived a median of 10 months.

“The combination of venetoclax and gilteritinib was tolerable at standard doses of each drug, generated remarkably high response rates, and markedly reduced FLT3-internal tandem duplications mutation burden. … Early mortality was similar to gilteritinib monotherapy,” the authors wrote.

Eighty percent of patients experienced cytopenias, and “adverse events prompted venetoclax and gilteritinib dose interruptions in 51% and 48%, respectively.”

About 60% of patients who went on to receive allogeneic hematopoietic stem cell transplantation were alive at the end of follow-up, “suggesting that VenGilt [the combo treatment] could be an effective bridge to transplant in young/fit patients with relapsed FLT3mut AML,” the researchers wrote.

All patients withdrew from the study by November 2021 for several reasons such as death (n=42), adverse events (n=10), and disease progression (29); some had multiple reasons.

Dr. Brunner said the study is “an important step toward evaluating a new potential regimen.”

The remission duration, FLT3 molecular response, and median overall survival “seem quite encouraging for a severe disease like AML in relapse,” he said. However, he added that the drug combo “would need to be evaluated in a randomized and, ideally, placebo-controlled setting to know if this is a significant improvement.”

He also highlighted the high number of severe cyptopenias with associated complications such as death. “Whether this is acceptable depends on the patient and circumstances,” he said. “But it does suggest that this regimen would potentially be for more robust patients, particularly since the group that did best were those who went to transplant later.”

Pending more research, Dr. Brunner said, “I am not sure I would use [the combination treatment] over gilteritinib monotherapy, for instance. But there may be settings where no other options are available, and this could be considered, particularly if a transplant option is a next step.”

The study was funded by AbbVie, Genentech, and Astellas. The study authors report multiple disclosures; some are employed by Astellas, AbbVie, and Genentech/Roche.

Dr. Bronner reports running clinical trials, advisory board service and/or consultation for Acceleron, Agios, Abbvie, BMS/Celgene, Keros Therapeutics, Novartis, Takeda, GSK, AstraZeneca, Janssen, and Gilead.

Adding venetoclax (Venclexta) to a gilteritinib (Xospata) regimen appeared to improve outcomes in refractory/relapsed FLT3-mutated acute myeloid leukemia (AML), a new industry-funded phase 1b study reported.

“The combination of venetoclax and gilteritinib is a highly active and tolerable oral combination regimen that potentially improves response frequency and depth over existing standards in a high-risk, mutation-defined group of patients with AML,” wrote the authors of the study, which appeared in the Journal of Clinical Oncology.

Outcomes in AML are poor. As the study notes, most patients relapse and face a median overall survival of 4-7 months even with standard chemotherapy. Gilteritinib, a selective oral FLT3 inhibitor, is Food and Drug Administration–approved for the 30% of relapsed/refractory patients with AML who have FLT3 mutations.

“The general sentiment is that, although some patients have great benefit from gilteritinib monotherapy, there is room to improve the quality, frequency, and duration of responses with combinations,” said hematologist Andrew Brunner, MD, of Massachusetts General Hospital in Boston, in an interview. He was not involved with the study research.

For the new open-label, dose-escalation/dose-expansion study, led by hematologist Naval Daver, MD, of the University of Texas MD Anderson Cancer Center, Houston, researchers enrolled 61 patients (56 with FLT3 mutations) from 2018 to 2020. The median age was 63 years (range 21-85).

The subjects were assigned to get a recommended phase 2 dose of 400 mg venetoclax once daily and 120 mg gilteritinib once daily.

Over a median follow-up of 17.5 months, the median remission time was 4.9 months (95% confidence interval, 3.4-6.6), and the patients with FLT3 mutations survived a median of 10 months.

“The combination of venetoclax and gilteritinib was tolerable at standard doses of each drug, generated remarkably high response rates, and markedly reduced FLT3-internal tandem duplications mutation burden. … Early mortality was similar to gilteritinib monotherapy,” the authors wrote.

Eighty percent of patients experienced cytopenias, and “adverse events prompted venetoclax and gilteritinib dose interruptions in 51% and 48%, respectively.”

About 60% of patients who went on to receive allogeneic hematopoietic stem cell transplantation were alive at the end of follow-up, “suggesting that VenGilt [the combo treatment] could be an effective bridge to transplant in young/fit patients with relapsed FLT3mut AML,” the researchers wrote.

All patients withdrew from the study by November 2021 for several reasons such as death (n=42), adverse events (n=10), and disease progression (29); some had multiple reasons.

Dr. Brunner said the study is “an important step toward evaluating a new potential regimen.”

The remission duration, FLT3 molecular response, and median overall survival “seem quite encouraging for a severe disease like AML in relapse,” he said. However, he added that the drug combo “would need to be evaluated in a randomized and, ideally, placebo-controlled setting to know if this is a significant improvement.”

He also highlighted the high number of severe cyptopenias with associated complications such as death. “Whether this is acceptable depends on the patient and circumstances,” he said. “But it does suggest that this regimen would potentially be for more robust patients, particularly since the group that did best were those who went to transplant later.”

Pending more research, Dr. Brunner said, “I am not sure I would use [the combination treatment] over gilteritinib monotherapy, for instance. But there may be settings where no other options are available, and this could be considered, particularly if a transplant option is a next step.”

The study was funded by AbbVie, Genentech, and Astellas. The study authors report multiple disclosures; some are employed by Astellas, AbbVie, and Genentech/Roche.

Dr. Bronner reports running clinical trials, advisory board service and/or consultation for Acceleron, Agios, Abbvie, BMS/Celgene, Keros Therapeutics, Novartis, Takeda, GSK, AstraZeneca, Janssen, and Gilead.

When Lynda Carter talks about her late husband Robert Altman, you can sense right away that this was a love affair for the ages.

“As I’ve often said, if you were a friend of Robert’s, you were one of the luckiest people in the world,” said Ms. Carter, the singer-songwriter and actor best known for her role as Wonder Woman in the 1970s TV series, who married Mr. Altman, an attorney, in 1984.

For Ms. Carter, Mr. Altman, and their children, Jessica and James, everything changed in 2017, when Mr. Altman was diagnosed with myelofibrosis, a rare bone marrow disorder – about one case is reported per 100,000 Americans each year – that was found during routine blood work.

“Robert was never sick a day in his life,” she said in an interview. “He skied and swam, and in many ways we were in the prime of our lives together. When he was initially diagnosed, we weren’t even clear what he had. The buzzword was that he had a rare blood disorder, not cancer.”

The family was told to wait and see if the disease would get worse, which it did, unfortunately, at the exact time COVID-19 hit.

This condition can progress from myelofibrosis to secondary acute myeloid leukemia, a rare blood cancer, said Michael Caligiuri, MD, a leading researcher in immunology, lymphoma, and leukemia and president of City of Hope National Medical Center, Duarte, Calif., one of the largest cancer research and treatment organizations in the United States.

“This disease is chronic and slow changing, but when it progresses more acutely to a form of leukemia, it can advance rapidly,” he said.

At the acute phase, there’s not much that can be done for the patient.

“This becomes very much a life-and-death situation,” he said. “You want to hope for the best, but there needs to be an expectation of the worst in terms of trying to prepare the patient and the family for what may come so that they can start to psychologically and legally put the person’s life in order.”

Despite every effort, Mr. Altman died in February 2021 at the age of 73.

Now, to honor her husband, Ms. Carter is gifting her time and resources to create the Robert & Lynda Carter Altman Family Foundation Research Fund, working with the Translational Genomics Research Institute, a leading biomedical research institute at City of Hope.

The goal: To speed up critical research that will improve early detection and survival for this hard-to-treat blood cancer.

“I’m excited to be a part of this team and to know that I may play a small part in helping other families facing this same diagnosis,” Ms. Carter said. “It’s thrilling seeing the progress these scientists are making, from genomic research into a universe of trillions of codes that might actually become a drug therapy someday.”

With the creation of the foundation, there will be funding to develop better diagnostics and better treatments.

“In many instances, this research will shed light on other related disorders, too,” said Dr. Caligiuri. “Cancer is a disease of the genes, and in most cases, we’re not inheriting from our mothers or fathers, but the DNA gets switched around in one of the trillion cells in our body, the way a word is misspelled.”

What happens next is that the cell doesn’t die.

“Instead, it undergoes a nuclear reaction and grows and grows,” he said. “In this case, the first evidence of a problem was myelofibrosis. That ticking time bomb continued until it exploded into leukemia.”

Dr. Caligiuri said the goal of their research will be to develop a device that can rearrange that DNA or block the DNA changes so the disease doesn’t progress to leukemia or, if it does, so “that we can turn it into a chronic condition, not an acute one that’s life-threatening.”

For Ms. Carter, this foundation is one very heartfelt way that she can honor her husband’s legacy.

“When I lost Robert, I was left with so many questions,” she said. “I wanted to understand why rare cancers are so difficult to treat and what research or treatment advances were being made to change that. Robert was never one for self-aggrandizement, but I think he would like this. I think Robert would really be touched by this.”

A version of this article first appeared on WebMD.com.

When Lynda Carter talks about her late husband Robert Altman, you can sense right away that this was a love affair for the ages.

“As I’ve often said, if you were a friend of Robert’s, you were one of the luckiest people in the world,” said Ms. Carter, the singer-songwriter and actor best known for her role as Wonder Woman in the 1970s TV series, who married Mr. Altman, an attorney, in 1984.

For Ms. Carter, Mr. Altman, and their children, Jessica and James, everything changed in 2017, when Mr. Altman was diagnosed with myelofibrosis, a rare bone marrow disorder – about one case is reported per 100,000 Americans each year – that was found during routine blood work.

“Robert was never sick a day in his life,” she said in an interview. “He skied and swam, and in many ways we were in the prime of our lives together. When he was initially diagnosed, we weren’t even clear what he had. The buzzword was that he had a rare blood disorder, not cancer.”

The family was told to wait and see if the disease would get worse, which it did, unfortunately, at the exact time COVID-19 hit.

This condition can progress from myelofibrosis to secondary acute myeloid leukemia, a rare blood cancer, said Michael Caligiuri, MD, a leading researcher in immunology, lymphoma, and leukemia and president of City of Hope National Medical Center, Duarte, Calif., one of the largest cancer research and treatment organizations in the United States.

“This disease is chronic and slow changing, but when it progresses more acutely to a form of leukemia, it can advance rapidly,” he said.

At the acute phase, there’s not much that can be done for the patient.

“This becomes very much a life-and-death situation,” he said. “You want to hope for the best, but there needs to be an expectation of the worst in terms of trying to prepare the patient and the family for what may come so that they can start to psychologically and legally put the person’s life in order.”

Despite every effort, Mr. Altman died in February 2021 at the age of 73.

Now, to honor her husband, Ms. Carter is gifting her time and resources to create the Robert & Lynda Carter Altman Family Foundation Research Fund, working with the Translational Genomics Research Institute, a leading biomedical research institute at City of Hope.

The goal: To speed up critical research that will improve early detection and survival for this hard-to-treat blood cancer.

“I’m excited to be a part of this team and to know that I may play a small part in helping other families facing this same diagnosis,” Ms. Carter said. “It’s thrilling seeing the progress these scientists are making, from genomic research into a universe of trillions of codes that might actually become a drug therapy someday.”

With the creation of the foundation, there will be funding to develop better diagnostics and better treatments.

“In many instances, this research will shed light on other related disorders, too,” said Dr. Caligiuri. “Cancer is a disease of the genes, and in most cases, we’re not inheriting from our mothers or fathers, but the DNA gets switched around in one of the trillion cells in our body, the way a word is misspelled.”

What happens next is that the cell doesn’t die.

“Instead, it undergoes a nuclear reaction and grows and grows,” he said. “In this case, the first evidence of a problem was myelofibrosis. That ticking time bomb continued until it exploded into leukemia.”

Dr. Caligiuri said the goal of their research will be to develop a device that can rearrange that DNA or block the DNA changes so the disease doesn’t progress to leukemia or, if it does, so “that we can turn it into a chronic condition, not an acute one that’s life-threatening.”

For Ms. Carter, this foundation is one very heartfelt way that she can honor her husband’s legacy.

“When I lost Robert, I was left with so many questions,” she said. “I wanted to understand why rare cancers are so difficult to treat and what research or treatment advances were being made to change that. Robert was never one for self-aggrandizement, but I think he would like this. I think Robert would really be touched by this.”

A version of this article first appeared on WebMD.com.

When Lynda Carter talks about her late husband Robert Altman, you can sense right away that this was a love affair for the ages.

“As I’ve often said, if you were a friend of Robert’s, you were one of the luckiest people in the world,” said Ms. Carter, the singer-songwriter and actor best known for her role as Wonder Woman in the 1970s TV series, who married Mr. Altman, an attorney, in 1984.

For Ms. Carter, Mr. Altman, and their children, Jessica and James, everything changed in 2017, when Mr. Altman was diagnosed with myelofibrosis, a rare bone marrow disorder – about one case is reported per 100,000 Americans each year – that was found during routine blood work.

“Robert was never sick a day in his life,” she said in an interview. “He skied and swam, and in many ways we were in the prime of our lives together. When he was initially diagnosed, we weren’t even clear what he had. The buzzword was that he had a rare blood disorder, not cancer.”

The family was told to wait and see if the disease would get worse, which it did, unfortunately, at the exact time COVID-19 hit.

This condition can progress from myelofibrosis to secondary acute myeloid leukemia, a rare blood cancer, said Michael Caligiuri, MD, a leading researcher in immunology, lymphoma, and leukemia and president of City of Hope National Medical Center, Duarte, Calif., one of the largest cancer research and treatment organizations in the United States.

“This disease is chronic and slow changing, but when it progresses more acutely to a form of leukemia, it can advance rapidly,” he said.

At the acute phase, there’s not much that can be done for the patient.

“This becomes very much a life-and-death situation,” he said. “You want to hope for the best, but there needs to be an expectation of the worst in terms of trying to prepare the patient and the family for what may come so that they can start to psychologically and legally put the person’s life in order.”

Despite every effort, Mr. Altman died in February 2021 at the age of 73.

Now, to honor her husband, Ms. Carter is gifting her time and resources to create the Robert & Lynda Carter Altman Family Foundation Research Fund, working with the Translational Genomics Research Institute, a leading biomedical research institute at City of Hope.

The goal: To speed up critical research that will improve early detection and survival for this hard-to-treat blood cancer.

“I’m excited to be a part of this team and to know that I may play a small part in helping other families facing this same diagnosis,” Ms. Carter said. “It’s thrilling seeing the progress these scientists are making, from genomic research into a universe of trillions of codes that might actually become a drug therapy someday.”

With the creation of the foundation, there will be funding to develop better diagnostics and better treatments.

“In many instances, this research will shed light on other related disorders, too,” said Dr. Caligiuri. “Cancer is a disease of the genes, and in most cases, we’re not inheriting from our mothers or fathers, but the DNA gets switched around in one of the trillion cells in our body, the way a word is misspelled.”

What happens next is that the cell doesn’t die.

“Instead, it undergoes a nuclear reaction and grows and grows,” he said. “In this case, the first evidence of a problem was myelofibrosis. That ticking time bomb continued until it exploded into leukemia.”

Dr. Caligiuri said the goal of their research will be to develop a device that can rearrange that DNA or block the DNA changes so the disease doesn’t progress to leukemia or, if it does, so “that we can turn it into a chronic condition, not an acute one that’s life-threatening.”

For Ms. Carter, this foundation is one very heartfelt way that she can honor her husband’s legacy.

“When I lost Robert, I was left with so many questions,” she said. “I wanted to understand why rare cancers are so difficult to treat and what research or treatment advances were being made to change that. Robert was never one for self-aggrandizement, but I think he would like this. I think Robert would really be touched by this.”

A version of this article first appeared on WebMD.com.