TBD Meeting (3270-21)

Nearly every patient with a myeloid malignancy seroconverted against COVID-19 after their second dose of the Moderna vaccine in a review of 46 patients at the Moffitt Cancer Center in Tampa, Fla.

Factors including age, gender, race, disease status, lower-intensity active treatment, baseline neutrophil and lymphocyte counts, and past history of stem cell transplant had no effects on seroconversion in the study, which, despite its small numbers, is one of the largest series to date among patients with myeloid cancers. The findings were reported at the annual meeting of the American Society of Hematology.

COVID vaccination “appears to induce a strong antibody response” in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), unlike with B-cell malignancies. “It indicates we should be aggressive about vaccinating such patients,” said senior investigator Jeffrey Lancet, MD, a blood cancer specialist at Moffitt, when he presented the findings at the meeting.

Presentation moderator Laura Michaelis, MD, a hematologist-oncologist at the Medical College of Wisconsin, Milwaukee, agreed.

The “strong antibody response in this group,” coupled with its high risk for severe COVID, “confirm the importance of these patients getting vaccinated,” she said.

Thirty patients with AML and 16 with MDS were included in the review. Most patients were in remission at the time of vaccination, but a third were in active treatment, including six on hypomethylating agents, six on targeted therapies, two on luspatercept, and one on lenalidomide. Thirty-two patients (69.6%) were a median of 17 months past allogeneic stem cell transplant.

Overall, 69.6% of patients developed IgG against spike proteins after the first shot and 95.7% of patients after the second dose, with a large increase in titer levels from the first to the second dose, from a mean of 315 AU/mL to 3,806.5 AU/mL following the second dose.

“Lab and clinical variables did not affect the antibody positivity rate after the second dose,” but patients on steroids and other immunosuppressants seemed less likely to respond to the first shot, Dr. Lancet said.

The study, conducted in early 2021, did not include acutely ill patients or those undergoing cheomotherapy induction and other aggressive treatments, because such patients were not being vaccinated at Moffitt during the study period.

The investigators measured anti-spike IgG by ELISA at baseline, then again about a month after the first shot and a month after the second shot.

Side effects were common and typically mild, including injection site pain, fatigue, headache, and arm swelling. Two patients with AML relapsed after vaccination.

Patients were a median of 68 years old when they were vaccinated; 58.7% were men; and almost all of the subjects were White. The median time from diagnosis to the first shot was 2 years.

The next step in the project is to study the timing of vaccination and response to it among patients on aggressive treatment and to perform neutralizing antibody assays to correlate IgG response with protection from COVID.

No funding was reported for the study. Investigators had numerous industry ties, including Dr. Lancet, a consultant for Celgene/BMS, Millenium Pharma/Takeda, AbbVie, and other firms. Dr. Michaelis didn’t have any disclosures.

aotto@mdedge.com

Nearly every patient with a myeloid malignancy seroconverted against COVID-19 after their second dose of the Moderna vaccine in a review of 46 patients at the Moffitt Cancer Center in Tampa, Fla.

Factors including age, gender, race, disease status, lower-intensity active treatment, baseline neutrophil and lymphocyte counts, and past history of stem cell transplant had no effects on seroconversion in the study, which, despite its small numbers, is one of the largest series to date among patients with myeloid cancers. The findings were reported at the annual meeting of the American Society of Hematology.

COVID vaccination “appears to induce a strong antibody response” in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), unlike with B-cell malignancies. “It indicates we should be aggressive about vaccinating such patients,” said senior investigator Jeffrey Lancet, MD, a blood cancer specialist at Moffitt, when he presented the findings at the meeting.

Presentation moderator Laura Michaelis, MD, a hematologist-oncologist at the Medical College of Wisconsin, Milwaukee, agreed.

The “strong antibody response in this group,” coupled with its high risk for severe COVID, “confirm the importance of these patients getting vaccinated,” she said.

Thirty patients with AML and 16 with MDS were included in the review. Most patients were in remission at the time of vaccination, but a third were in active treatment, including six on hypomethylating agents, six on targeted therapies, two on luspatercept, and one on lenalidomide. Thirty-two patients (69.6%) were a median of 17 months past allogeneic stem cell transplant.

Overall, 69.6% of patients developed IgG against spike proteins after the first shot and 95.7% of patients after the second dose, with a large increase in titer levels from the first to the second dose, from a mean of 315 AU/mL to 3,806.5 AU/mL following the second dose.

“Lab and clinical variables did not affect the antibody positivity rate after the second dose,” but patients on steroids and other immunosuppressants seemed less likely to respond to the first shot, Dr. Lancet said.

The study, conducted in early 2021, did not include acutely ill patients or those undergoing cheomotherapy induction and other aggressive treatments, because such patients were not being vaccinated at Moffitt during the study period.

The investigators measured anti-spike IgG by ELISA at baseline, then again about a month after the first shot and a month after the second shot.

Side effects were common and typically mild, including injection site pain, fatigue, headache, and arm swelling. Two patients with AML relapsed after vaccination.

Patients were a median of 68 years old when they were vaccinated; 58.7% were men; and almost all of the subjects were White. The median time from diagnosis to the first shot was 2 years.

The next step in the project is to study the timing of vaccination and response to it among patients on aggressive treatment and to perform neutralizing antibody assays to correlate IgG response with protection from COVID.

No funding was reported for the study. Investigators had numerous industry ties, including Dr. Lancet, a consultant for Celgene/BMS, Millenium Pharma/Takeda, AbbVie, and other firms. Dr. Michaelis didn’t have any disclosures.

aotto@mdedge.com

Nearly every patient with a myeloid malignancy seroconverted against COVID-19 after their second dose of the Moderna vaccine in a review of 46 patients at the Moffitt Cancer Center in Tampa, Fla.

Factors including age, gender, race, disease status, lower-intensity active treatment, baseline neutrophil and lymphocyte counts, and past history of stem cell transplant had no effects on seroconversion in the study, which, despite its small numbers, is one of the largest series to date among patients with myeloid cancers. The findings were reported at the annual meeting of the American Society of Hematology.

COVID vaccination “appears to induce a strong antibody response” in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), unlike with B-cell malignancies. “It indicates we should be aggressive about vaccinating such patients,” said senior investigator Jeffrey Lancet, MD, a blood cancer specialist at Moffitt, when he presented the findings at the meeting.

Presentation moderator Laura Michaelis, MD, a hematologist-oncologist at the Medical College of Wisconsin, Milwaukee, agreed.

The “strong antibody response in this group,” coupled with its high risk for severe COVID, “confirm the importance of these patients getting vaccinated,” she said.

Thirty patients with AML and 16 with MDS were included in the review. Most patients were in remission at the time of vaccination, but a third were in active treatment, including six on hypomethylating agents, six on targeted therapies, two on luspatercept, and one on lenalidomide. Thirty-two patients (69.6%) were a median of 17 months past allogeneic stem cell transplant.

Overall, 69.6% of patients developed IgG against spike proteins after the first shot and 95.7% of patients after the second dose, with a large increase in titer levels from the first to the second dose, from a mean of 315 AU/mL to 3,806.5 AU/mL following the second dose.

“Lab and clinical variables did not affect the antibody positivity rate after the second dose,” but patients on steroids and other immunosuppressants seemed less likely to respond to the first shot, Dr. Lancet said.

The study, conducted in early 2021, did not include acutely ill patients or those undergoing cheomotherapy induction and other aggressive treatments, because such patients were not being vaccinated at Moffitt during the study period.

The investigators measured anti-spike IgG by ELISA at baseline, then again about a month after the first shot and a month after the second shot.

Side effects were common and typically mild, including injection site pain, fatigue, headache, and arm swelling. Two patients with AML relapsed after vaccination.

Patients were a median of 68 years old when they were vaccinated; 58.7% were men; and almost all of the subjects were White. The median time from diagnosis to the first shot was 2 years.

The next step in the project is to study the timing of vaccination and response to it among patients on aggressive treatment and to perform neutralizing antibody assays to correlate IgG response with protection from COVID.

No funding was reported for the study. Investigators had numerous industry ties, including Dr. Lancet, a consultant for Celgene/BMS, Millenium Pharma/Takeda, AbbVie, and other firms. Dr. Michaelis didn’t have any disclosures.

aotto@mdedge.com

An experimental bi-specific monoclonal antibody known as mosunetuzumab has induced high response rates and long-duration responses as monotherapy for patients with heavily pretreated, relapsed or refractory follicular lymphoma in a phase 2 expansion study.

At a median follow-up of 18.3 months, 54 of 90 patients (60%) had a complete response, and 18 (20%) had a partial response after treatment with mosunetuzumab, reported L. Elizabeth Budde, MD, PhD, from City of Hope Comprehensive Cancer Center in Duarte, Calif.

In contrast, the complete response rate for historical controls was just 14% (P < .0001), Dr. Budde noted.

“We have seen deep and durable responses in heavily pretreated, high-risk relapsed/refractory follicular lymphoma patients with fixed-duration treatment. We also observed a very favorable tolerability profile, with most cytokine release syndrome confined to cycle 1 and low grade, and treatment administration is without mandatory hospitalization,” she commented.

Budde was speaking at a press briefing prior to her presentation of the data at the annual meeting of the American Society of Hematology (ASH), held in a hybrid live/virtual format.

The manufacturer, Genentech, said in a statement that based on these “highly positive results,” it plans to submit the new data to the U.S. Food and Drug Administration (FDA) in the near future for approval consideration.

If approved, mosunetuzumab has the potential to be a first-in-class CD20xCD3 T-cell engaging bispecific antibody in non-Hodgkin lymphoma, the company added.

“Outstanding” data

A lymphoma specialist who was not involved in the study told this news organization that he was favorably impressed by the findings.

“To me, the single-agent data looks really outstanding, with a response rate of 80%, a complete response rate of 60%, and a median duration of response of 23 months, and really very acceptable rates of cytokine release syndrome,” commented Brad S. Kahl, MD, from the Siteman Cancer Center and Washington University School of Medicine in St. Louis.

“I think as a single agent — if it does get approval — it will be a really valuable addition to the armamentarium in follicular lymphoma,” he said.

Dr. Kahl pointed to a separate phase 1b study, also presented at the meeting, suggesting that the combination of mosunetuzumab and lenalidomide (Revlimid) was safe and showed promising antitumor activity in patients with follicular lymphoma that has relapsed after at least 1 line of therapy.

“I’m very interested to see how mosunetuzumab plus lenalidomide pans out in the long run,” he said.

Study details

Mosunetuzumab engages T cells and redirects them to eliminate malignant B cells. It has the potential to be used as an off-the-shelf product, Dr. Budde said.

In the single-arm phase 2 expansion trial, Dr. Budde and colleagues enrolled 90 patients with grades 1 to 3a follicular lymphoma whose disease relapsed or was refractory to at least two prior lines of therapy, including at least one anti-CD20 monoclonal antibody, and at least one alkylating agent.

Patients were treated with step-up dosing for the first 21-day cycle to mitigate the cytokine release syndrome. They then received eight cycles if they had a complete response, and 17 cycles if they had a partial response or stable disease after eight cycles.

The primary endpoint was complete response rate by independent review, which was 60%, and the overall response rate (ORR), a secondary efficacy endpoint, was 80%.

There were no significant differences in CR or ORR rates among subgroups according to patient age, number of prior lines of therapy, relapsed or refractory disease to last prior line of therapy, double-refractory disease, or disease progression within 24 months of primary therapy.

The median duration of response among all responders was 22.8 months, with a median time to first response of 1.4 months. The 12- and 18-months event-free rates were 62% and 57%, respectively.

The safety profile was manageable, Dr. Budde said, with grade 3 or 4 drug-related adverse events occurring in about half of patients, and serious adverse events occurring in a third.

There were two deaths during the study, but neither was judged to be related to mosunetuzumab, and there were only two events leading to drug discontinuation.

Cytokine release syndrome (CRS) of any grade occurred in 40 patients (44.4%), but only 1 patient each had a grade 3 or 4 CR. The median time to CRS onset was 5.2 hours in cycle 1, and 26.6 hours in subsequent cycles. The median duration of CRS was 3 days. Ten patients had CRS managed with corticosteroids, and seven had it managed with tocilizumab.

Immune effector cell-associated neurotoxicity syndrome (ICANS) events were infrequent, and all were grade 1 or 2 in severity.

The study was supported by Genentech. Dr. Budde disclosed consulting for the company and others. Dr. Kahl has previously disclosed financial considerations with AbbVie.



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

This article was updated 12/12/21.

An experimental bi-specific monoclonal antibody known as mosunetuzumab has induced high response rates and long-duration responses as monotherapy for patients with heavily pretreated, relapsed or refractory follicular lymphoma in a phase 2 expansion study.

At a median follow-up of 18.3 months, 54 of 90 patients (60%) had a complete response, and 18 (20%) had a partial response after treatment with mosunetuzumab, reported L. Elizabeth Budde, MD, PhD, from City of Hope Comprehensive Cancer Center in Duarte, Calif.

In contrast, the complete response rate for historical controls was just 14% (P < .0001), Dr. Budde noted.

“We have seen deep and durable responses in heavily pretreated, high-risk relapsed/refractory follicular lymphoma patients with fixed-duration treatment. We also observed a very favorable tolerability profile, with most cytokine release syndrome confined to cycle 1 and low grade, and treatment administration is without mandatory hospitalization,” she commented.

Budde was speaking at a press briefing prior to her presentation of the data at the annual meeting of the American Society of Hematology (ASH), held in a hybrid live/virtual format.

The manufacturer, Genentech, said in a statement that based on these “highly positive results,” it plans to submit the new data to the U.S. Food and Drug Administration (FDA) in the near future for approval consideration.

If approved, mosunetuzumab has the potential to be a first-in-class CD20xCD3 T-cell engaging bispecific antibody in non-Hodgkin lymphoma, the company added.

“Outstanding” data

A lymphoma specialist who was not involved in the study told this news organization that he was favorably impressed by the findings.

“To me, the single-agent data looks really outstanding, with a response rate of 80%, a complete response rate of 60%, and a median duration of response of 23 months, and really very acceptable rates of cytokine release syndrome,” commented Brad S. Kahl, MD, from the Siteman Cancer Center and Washington University School of Medicine in St. Louis.

“I think as a single agent — if it does get approval — it will be a really valuable addition to the armamentarium in follicular lymphoma,” he said.

Dr. Kahl pointed to a separate phase 1b study, also presented at the meeting, suggesting that the combination of mosunetuzumab and lenalidomide (Revlimid) was safe and showed promising antitumor activity in patients with follicular lymphoma that has relapsed after at least 1 line of therapy.

“I’m very interested to see how mosunetuzumab plus lenalidomide pans out in the long run,” he said.

Study details

Mosunetuzumab engages T cells and redirects them to eliminate malignant B cells. It has the potential to be used as an off-the-shelf product, Dr. Budde said.

In the single-arm phase 2 expansion trial, Dr. Budde and colleagues enrolled 90 patients with grades 1 to 3a follicular lymphoma whose disease relapsed or was refractory to at least two prior lines of therapy, including at least one anti-CD20 monoclonal antibody, and at least one alkylating agent.

Patients were treated with step-up dosing for the first 21-day cycle to mitigate the cytokine release syndrome. They then received eight cycles if they had a complete response, and 17 cycles if they had a partial response or stable disease after eight cycles.

The primary endpoint was complete response rate by independent review, which was 60%, and the overall response rate (ORR), a secondary efficacy endpoint, was 80%.

There were no significant differences in CR or ORR rates among subgroups according to patient age, number of prior lines of therapy, relapsed or refractory disease to last prior line of therapy, double-refractory disease, or disease progression within 24 months of primary therapy.

The median duration of response among all responders was 22.8 months, with a median time to first response of 1.4 months. The 12- and 18-months event-free rates were 62% and 57%, respectively.

The safety profile was manageable, Dr. Budde said, with grade 3 or 4 drug-related adverse events occurring in about half of patients, and serious adverse events occurring in a third.

There were two deaths during the study, but neither was judged to be related to mosunetuzumab, and there were only two events leading to drug discontinuation.

Cytokine release syndrome (CRS) of any grade occurred in 40 patients (44.4%), but only 1 patient each had a grade 3 or 4 CR. The median time to CRS onset was 5.2 hours in cycle 1, and 26.6 hours in subsequent cycles. The median duration of CRS was 3 days. Ten patients had CRS managed with corticosteroids, and seven had it managed with tocilizumab.

Immune effector cell-associated neurotoxicity syndrome (ICANS) events were infrequent, and all were grade 1 or 2 in severity.

The study was supported by Genentech. Dr. Budde disclosed consulting for the company and others. Dr. Kahl has previously disclosed financial considerations with AbbVie.



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

This article was updated 12/12/21.

An experimental bi-specific monoclonal antibody known as mosunetuzumab has induced high response rates and long-duration responses as monotherapy for patients with heavily pretreated, relapsed or refractory follicular lymphoma in a phase 2 expansion study.

At a median follow-up of 18.3 months, 54 of 90 patients (60%) had a complete response, and 18 (20%) had a partial response after treatment with mosunetuzumab, reported L. Elizabeth Budde, MD, PhD, from City of Hope Comprehensive Cancer Center in Duarte, Calif.

In contrast, the complete response rate for historical controls was just 14% (P < .0001), Dr. Budde noted.

“We have seen deep and durable responses in heavily pretreated, high-risk relapsed/refractory follicular lymphoma patients with fixed-duration treatment. We also observed a very favorable tolerability profile, with most cytokine release syndrome confined to cycle 1 and low grade, and treatment administration is without mandatory hospitalization,” she commented.

Budde was speaking at a press briefing prior to her presentation of the data at the annual meeting of the American Society of Hematology (ASH), held in a hybrid live/virtual format.

The manufacturer, Genentech, said in a statement that based on these “highly positive results,” it plans to submit the new data to the U.S. Food and Drug Administration (FDA) in the near future for approval consideration.

If approved, mosunetuzumab has the potential to be a first-in-class CD20xCD3 T-cell engaging bispecific antibody in non-Hodgkin lymphoma, the company added.

“Outstanding” data

A lymphoma specialist who was not involved in the study told this news organization that he was favorably impressed by the findings.

“To me, the single-agent data looks really outstanding, with a response rate of 80%, a complete response rate of 60%, and a median duration of response of 23 months, and really very acceptable rates of cytokine release syndrome,” commented Brad S. Kahl, MD, from the Siteman Cancer Center and Washington University School of Medicine in St. Louis.

“I think as a single agent — if it does get approval — it will be a really valuable addition to the armamentarium in follicular lymphoma,” he said.

Dr. Kahl pointed to a separate phase 1b study, also presented at the meeting, suggesting that the combination of mosunetuzumab and lenalidomide (Revlimid) was safe and showed promising antitumor activity in patients with follicular lymphoma that has relapsed after at least 1 line of therapy.

“I’m very interested to see how mosunetuzumab plus lenalidomide pans out in the long run,” he said.

Study details

Mosunetuzumab engages T cells and redirects them to eliminate malignant B cells. It has the potential to be used as an off-the-shelf product, Dr. Budde said.

In the single-arm phase 2 expansion trial, Dr. Budde and colleagues enrolled 90 patients with grades 1 to 3a follicular lymphoma whose disease relapsed or was refractory to at least two prior lines of therapy, including at least one anti-CD20 monoclonal antibody, and at least one alkylating agent.

Patients were treated with step-up dosing for the first 21-day cycle to mitigate the cytokine release syndrome. They then received eight cycles if they had a complete response, and 17 cycles if they had a partial response or stable disease after eight cycles.

The primary endpoint was complete response rate by independent review, which was 60%, and the overall response rate (ORR), a secondary efficacy endpoint, was 80%.

There were no significant differences in CR or ORR rates among subgroups according to patient age, number of prior lines of therapy, relapsed or refractory disease to last prior line of therapy, double-refractory disease, or disease progression within 24 months of primary therapy.

The median duration of response among all responders was 22.8 months, with a median time to first response of 1.4 months. The 12- and 18-months event-free rates were 62% and 57%, respectively.

The safety profile was manageable, Dr. Budde said, with grade 3 or 4 drug-related adverse events occurring in about half of patients, and serious adverse events occurring in a third.

There were two deaths during the study, but neither was judged to be related to mosunetuzumab, and there were only two events leading to drug discontinuation.

Cytokine release syndrome (CRS) of any grade occurred in 40 patients (44.4%), but only 1 patient each had a grade 3 or 4 CR. The median time to CRS onset was 5.2 hours in cycle 1, and 26.6 hours in subsequent cycles. The median duration of CRS was 3 days. Ten patients had CRS managed with corticosteroids, and seven had it managed with tocilizumab.

Immune effector cell-associated neurotoxicity syndrome (ICANS) events were infrequent, and all were grade 1 or 2 in severity.

The study was supported by Genentech. Dr. Budde disclosed consulting for the company and others. Dr. Kahl has previously disclosed financial considerations with AbbVie.



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

This article was updated 12/12/21.

Factors associated with the worst COVID-19-related outcomes for patients with acute leukemias and myelodysplastic syndromes include neutropenia, pre-COVID-19 prognosis, and deferral of ICU care, results of an American Society of Hematology (ASH) COVID-19 registry study suggest.

Rates of severe COVID-19 were significantly higher among patients who had active disease or neutropenia at the time of their COVID-19 diagnosis. Mortality related to COVID-19 was linked to neutropenia, primary disease prognosis of less than 6 months, and deferral of recommended ICU care, study results show.

By contrast, mortality was not associated with active primary disease or its treatment, according to researcher Pinkal Desai, MD, MPH.

Taken together, these findings provide preliminary evidence to support the use of aggressive supportive treatment of COVID-19 in patients with acute leukemias and myelodysplastic syndromes, said Dr. Desai, a hematologist-oncologist with Weill Cornell Medicine and NewYork-Presbyterian in New York.

“If desired by patients, aggressive support for hospitalized patients with COVID-19 is appropriate, regardless of remission status, given the results of our study,” Dr. Desai said in a press conference during the annual meeting of the American Society of Hematology.

In non-cancer patient populations, advanced age and cytopenias have been associated with mortality related to COVID-19, Dr. Desai said. Likewise, patients with acute leukemias and myelodysplastic syndrome are generally older and have disease- or treatment-related cytopenias, which might affect the severity of and mortality from COVID-19, she added.

With that concern in mind, Dr. Desai and co-investigators looked at predictors of severe COVID-19 disease and death among patients in the ASH Research Collaborative (ASH RC) COVID-19 Registry for Hematology.

This registry was started in the early days of the pandemic to provide real-time observational COVID-19 data to clinicians, according to an ASH news release.

The analysis by Dr. Desai and co-authors included 257 patients with COVID-19 as determined by their physician, including 135 with a primary diagnosis of acute myeloid leukemia, 82 with acute lymphocytic leukemia, and 40 with myelodysplastic syndromes. Sixty percent of the patients were hospitalized due to COVID-19.

At the time of COVID-19 diagnosis, 46% of patients were in remission, and 44% had active disease, according to the report.

Both neutropenia and active disease status at COVID-19 diagnosis were linked to severe COVID-19, defined as ICU admission due to a COVID-19-related reason, according to results of multivariable analysis. Among patients with severe COVID-19, 67% had active disease, meaning just 33% were in remission, Dr. Desai noted.

In multivariable analysis, two factors were significantly associated with mortality, she added: having an estimated pre-COVID-19 prognosis from the primary disease of less than 6 months, and deferral of ICU care when it was recommended to the patient.

Mortality was 21% overall, higher than would be expected in a non-cancer population, Dr. Desai said. For patients with COVID-19 requiring hospitalization, the mortality rate was 34% and for those patients who did go to the ICU, the mortality rate was 68%.

By contrast, there was no significant association between mortality and active disease as compared to disease in remission, Dr. Desai noted in her presentation. Likewise, mortality was not associated with active treatment at the time of COVID-19 diagnosis as compared to no treatment.

The Leukemia &amp; Lymphoma Society

Gwen Nichols, MD, executive vice president and chief medical officer of the Leukemia & Lymphoma Society, New York, said those are reassuring data for patients with acute leukemias and myelodysplastic syndromes and their healthcare providers.

“From our point of view, it helps us say, ‘do not stop your treatment because of worries about COVID-19—it’s more important that you treat your cancer,” Dr. Nichols said in an interview. “We now know we can help people through COVID-19, and I think this is just really important data to back that up,” she added.

Dr. Desai provided disclosures related to Agios, Kura Oncology, and Bristol Myers Squibb (consultancy), and to Janssen R&D and Astex (research funding).

Factors associated with the worst COVID-19-related outcomes for patients with acute leukemias and myelodysplastic syndromes include neutropenia, pre-COVID-19 prognosis, and deferral of ICU care, results of an American Society of Hematology (ASH) COVID-19 registry study suggest.

Rates of severe COVID-19 were significantly higher among patients who had active disease or neutropenia at the time of their COVID-19 diagnosis. Mortality related to COVID-19 was linked to neutropenia, primary disease prognosis of less than 6 months, and deferral of recommended ICU care, study results show.

By contrast, mortality was not associated with active primary disease or its treatment, according to researcher Pinkal Desai, MD, MPH.

Taken together, these findings provide preliminary evidence to support the use of aggressive supportive treatment of COVID-19 in patients with acute leukemias and myelodysplastic syndromes, said Dr. Desai, a hematologist-oncologist with Weill Cornell Medicine and NewYork-Presbyterian in New York.

“If desired by patients, aggressive support for hospitalized patients with COVID-19 is appropriate, regardless of remission status, given the results of our study,” Dr. Desai said in a press conference during the annual meeting of the American Society of Hematology.

In non-cancer patient populations, advanced age and cytopenias have been associated with mortality related to COVID-19, Dr. Desai said. Likewise, patients with acute leukemias and myelodysplastic syndrome are generally older and have disease- or treatment-related cytopenias, which might affect the severity of and mortality from COVID-19, she added.

With that concern in mind, Dr. Desai and co-investigators looked at predictors of severe COVID-19 disease and death among patients in the ASH Research Collaborative (ASH RC) COVID-19 Registry for Hematology.

This registry was started in the early days of the pandemic to provide real-time observational COVID-19 data to clinicians, according to an ASH news release.

The analysis by Dr. Desai and co-authors included 257 patients with COVID-19 as determined by their physician, including 135 with a primary diagnosis of acute myeloid leukemia, 82 with acute lymphocytic leukemia, and 40 with myelodysplastic syndromes. Sixty percent of the patients were hospitalized due to COVID-19.

At the time of COVID-19 diagnosis, 46% of patients were in remission, and 44% had active disease, according to the report.

Both neutropenia and active disease status at COVID-19 diagnosis were linked to severe COVID-19, defined as ICU admission due to a COVID-19-related reason, according to results of multivariable analysis. Among patients with severe COVID-19, 67% had active disease, meaning just 33% were in remission, Dr. Desai noted.

In multivariable analysis, two factors were significantly associated with mortality, she added: having an estimated pre-COVID-19 prognosis from the primary disease of less than 6 months, and deferral of ICU care when it was recommended to the patient.

Mortality was 21% overall, higher than would be expected in a non-cancer population, Dr. Desai said. For patients with COVID-19 requiring hospitalization, the mortality rate was 34% and for those patients who did go to the ICU, the mortality rate was 68%.

By contrast, there was no significant association between mortality and active disease as compared to disease in remission, Dr. Desai noted in her presentation. Likewise, mortality was not associated with active treatment at the time of COVID-19 diagnosis as compared to no treatment.

The Leukemia &amp; Lymphoma Society

Gwen Nichols, MD, executive vice president and chief medical officer of the Leukemia & Lymphoma Society, New York, said those are reassuring data for patients with acute leukemias and myelodysplastic syndromes and their healthcare providers.

“From our point of view, it helps us say, ‘do not stop your treatment because of worries about COVID-19—it’s more important that you treat your cancer,” Dr. Nichols said in an interview. “We now know we can help people through COVID-19, and I think this is just really important data to back that up,” she added.

Dr. Desai provided disclosures related to Agios, Kura Oncology, and Bristol Myers Squibb (consultancy), and to Janssen R&D and Astex (research funding).

Factors associated with the worst COVID-19-related outcomes for patients with acute leukemias and myelodysplastic syndromes include neutropenia, pre-COVID-19 prognosis, and deferral of ICU care, results of an American Society of Hematology (ASH) COVID-19 registry study suggest.

Rates of severe COVID-19 were significantly higher among patients who had active disease or neutropenia at the time of their COVID-19 diagnosis. Mortality related to COVID-19 was linked to neutropenia, primary disease prognosis of less than 6 months, and deferral of recommended ICU care, study results show.

By contrast, mortality was not associated with active primary disease or its treatment, according to researcher Pinkal Desai, MD, MPH.

Taken together, these findings provide preliminary evidence to support the use of aggressive supportive treatment of COVID-19 in patients with acute leukemias and myelodysplastic syndromes, said Dr. Desai, a hematologist-oncologist with Weill Cornell Medicine and NewYork-Presbyterian in New York.

“If desired by patients, aggressive support for hospitalized patients with COVID-19 is appropriate, regardless of remission status, given the results of our study,” Dr. Desai said in a press conference during the annual meeting of the American Society of Hematology.

In non-cancer patient populations, advanced age and cytopenias have been associated with mortality related to COVID-19, Dr. Desai said. Likewise, patients with acute leukemias and myelodysplastic syndrome are generally older and have disease- or treatment-related cytopenias, which might affect the severity of and mortality from COVID-19, she added.

With that concern in mind, Dr. Desai and co-investigators looked at predictors of severe COVID-19 disease and death among patients in the ASH Research Collaborative (ASH RC) COVID-19 Registry for Hematology.

This registry was started in the early days of the pandemic to provide real-time observational COVID-19 data to clinicians, according to an ASH news release.

The analysis by Dr. Desai and co-authors included 257 patients with COVID-19 as determined by their physician, including 135 with a primary diagnosis of acute myeloid leukemia, 82 with acute lymphocytic leukemia, and 40 with myelodysplastic syndromes. Sixty percent of the patients were hospitalized due to COVID-19.

At the time of COVID-19 diagnosis, 46% of patients were in remission, and 44% had active disease, according to the report.

Both neutropenia and active disease status at COVID-19 diagnosis were linked to severe COVID-19, defined as ICU admission due to a COVID-19-related reason, according to results of multivariable analysis. Among patients with severe COVID-19, 67% had active disease, meaning just 33% were in remission, Dr. Desai noted.

In multivariable analysis, two factors were significantly associated with mortality, she added: having an estimated pre-COVID-19 prognosis from the primary disease of less than 6 months, and deferral of ICU care when it was recommended to the patient.

Mortality was 21% overall, higher than would be expected in a non-cancer population, Dr. Desai said. For patients with COVID-19 requiring hospitalization, the mortality rate was 34% and for those patients who did go to the ICU, the mortality rate was 68%.

By contrast, there was no significant association between mortality and active disease as compared to disease in remission, Dr. Desai noted in her presentation. Likewise, mortality was not associated with active treatment at the time of COVID-19 diagnosis as compared to no treatment.

The Leukemia &amp; Lymphoma Society

Gwen Nichols, MD, executive vice president and chief medical officer of the Leukemia & Lymphoma Society, New York, said those are reassuring data for patients with acute leukemias and myelodysplastic syndromes and their healthcare providers.

“From our point of view, it helps us say, ‘do not stop your treatment because of worries about COVID-19—it’s more important that you treat your cancer,” Dr. Nichols said in an interview. “We now know we can help people through COVID-19, and I think this is just really important data to back that up,” she added.

Dr. Desai provided disclosures related to Agios, Kura Oncology, and Bristol Myers Squibb (consultancy), and to Janssen R&D and Astex (research funding).

In patients with transfusion-dependent beta-thalassemia, a single gene therapy infusion is capable of yielding durable transfusion independence and substantial improvements in iron overload, an investigator reported at the annual meeting of the American Society of Hematology.

Among patients who received betibeglogene autotemcel (beti-cel) in a phase 3 trial and enrolled in a long-term follow-up study, nearly 90% achieved durable transfusion independence, according to Alexis A. Thompson, MD, MPH, of the hematology section at the Ann & Robert H. Lurie Children’s Hospital of Chicago.

The median duration of ongoing transfusion independence was nearly 3 years as of this report, which Dr. Thompson described in a press conference at the meeting.

In a subanalysis of this international study, Dr. Thompson and co-investigators reported that in patients who achieve transfusion independence, chelation reduced iron, and iron markers stabilized even after chelation was stopped.

Beyond 2 years post-infusion, no adverse events related to the drug product were seen. This suggested that the therapy has a favorable long-term safety profile, according to Dr. Thompson.

“At this point, we believe that beti-cel is potentially curative for patients with TDT [transfusion-dependent beta-thalassemia],” Dr. Thompson said in the press conference.

This study answers one of the major outstanding questions about beti-cel and iron metabolism, according to Arielle L. Langer, MD, MPH, an instructor in medicine at Harvard Medical School and attending physician for adult thalassemia patients at Brigham and Women’s and Dana Farber Cancer Institute, both in Boston.

“Seeing the restoration of iron metabolism, it really takes us a step closer to really thinking the term ‘cure’ might truly apply,” Dr. Langer said in an interview.

Dr. Langer said she looks forward to “very long-term outcomes” of beti-cel-treated patients to see whether endocrinopathies and other long-term sequelae of TDT are also abated.

“This [study] is a great intermediate point, but really, when we think about how thalassemia harms and kills our patients, we really sometimes measure that in decades,” she said.

Beta-thalassemia is caused by mutations in the beta-globin gene, resulting in reduced levels of hemoglobin. Patients with TDT, the most serious form of the disease, have severe anemia and are often dependent on red blood cell transfusions from infancy onward, Dr. Thompson said.

With chronic transfusions needed to maintain hemoglobin levels, TDT patients inevitably experience iron overload, which can lead to organ damage and can be fatal. Consequently, patients will require lifelong iron chelation therapy, she added.

Beti-cel, an investigational ex vivo gene addition therapy currently under review by the U.S. Food and Drug Administration, involves adding functional copies of a modified form of the beta-globin gene into a patient’s own hematopoietic stem cells. Once those cells are reinfused, patients may produce adult hemoglobin at levels that eliminate the need for transfusions, according to Dr. Thompson.

At the meeting, Dr. Thompson reported on patients from two phase 1/2 and two phase 3 beti-cel clinical trials who subsequently enrolled in LTF-303, a 13-year follow-up study of the gene therapy’s safety and efficacy.

A total of 57 patients were included in this report, making it the largest gene therapy program to date in any blood disorder, according to Dr. Thompson. Before receiving beti-cel, the patients, who had a broad range of thalassemia genotypes, were receiving between 10 and almost 40 red blood cell transfusions per year, she reported.

Patients ranged in age from 5 to 35 years. The median age in the phase 1/2 studies was 20 years, while in the phase 3 studies it was 15 years.

“The early experience in the phase 1/2 trials allowed us to be more comfortable with enrolling more children, and that has actually helped us to understand safety and efficacy and children in the phase 3 setting,” Dr. Thompson said.

Fertility preservation measures had been undertaken by about 59% of patients from the phase 1/2 studies and 71% of patients from the phase 3 studies, the data show.

Among patients from the phase 3 beti-cel studies who could be evaluated, 31 out of 35 (or 89%) achieved durable transfusion independence, according to the investigator.

The median duration of ongoing transfusion independence was 32 months, with a range of about 18 to 49 months, she added.

Dr. Thompson also reported a subanalysis intended to assess iron status in 16 patients who restarted and then stopped chelation. That subanalysis demonstrated iron reduction in response to chelation, and then stabilization of iron markers after chelation was stopped. Post-gene therapy chelation led to reductions in liver iron concentration and serum ferritin that remained relatively stable after chelation was stopped, she said.

Serious adverse events occurred in eight patients in the long-term follow-up study. However, adverse events related to beti-cel have been absent beyond 2 years post-infusion, according to Dr. Thompson, who added that there have been no reported cases of replication-competent lentivirus, no clonal expansion, no insertional oncogenesis, and no malignancies observed.

“Very reassuringly, there have been 2 male patients, one of whom underwent fertility preservation, who report having healthy children with their partners,” she added.

Dr. Thompson provided disclosures related to Baxalta, Biomarin, bluebird bio, Inc., Celgene/BMS, CRISPR Therapeutics, Vertex, Editas, Graphite Bio, Novartis, Agios, Beam, and Global Blood Therapeutics.
 

In patients with transfusion-dependent beta-thalassemia, a single gene therapy infusion is capable of yielding durable transfusion independence and substantial improvements in iron overload, an investigator reported at the annual meeting of the American Society of Hematology.

Among patients who received betibeglogene autotemcel (beti-cel) in a phase 3 trial and enrolled in a long-term follow-up study, nearly 90% achieved durable transfusion independence, according to Alexis A. Thompson, MD, MPH, of the hematology section at the Ann & Robert H. Lurie Children’s Hospital of Chicago.

The median duration of ongoing transfusion independence was nearly 3 years as of this report, which Dr. Thompson described in a press conference at the meeting.

In a subanalysis of this international study, Dr. Thompson and co-investigators reported that in patients who achieve transfusion independence, chelation reduced iron, and iron markers stabilized even after chelation was stopped.

Beyond 2 years post-infusion, no adverse events related to the drug product were seen. This suggested that the therapy has a favorable long-term safety profile, according to Dr. Thompson.

“At this point, we believe that beti-cel is potentially curative for patients with TDT [transfusion-dependent beta-thalassemia],” Dr. Thompson said in the press conference.

This study answers one of the major outstanding questions about beti-cel and iron metabolism, according to Arielle L. Langer, MD, MPH, an instructor in medicine at Harvard Medical School and attending physician for adult thalassemia patients at Brigham and Women’s and Dana Farber Cancer Institute, both in Boston.

“Seeing the restoration of iron metabolism, it really takes us a step closer to really thinking the term ‘cure’ might truly apply,” Dr. Langer said in an interview.

Dr. Langer said she looks forward to “very long-term outcomes” of beti-cel-treated patients to see whether endocrinopathies and other long-term sequelae of TDT are also abated.

“This [study] is a great intermediate point, but really, when we think about how thalassemia harms and kills our patients, we really sometimes measure that in decades,” she said.

Beta-thalassemia is caused by mutations in the beta-globin gene, resulting in reduced levels of hemoglobin. Patients with TDT, the most serious form of the disease, have severe anemia and are often dependent on red blood cell transfusions from infancy onward, Dr. Thompson said.

With chronic transfusions needed to maintain hemoglobin levels, TDT patients inevitably experience iron overload, which can lead to organ damage and can be fatal. Consequently, patients will require lifelong iron chelation therapy, she added.

Beti-cel, an investigational ex vivo gene addition therapy currently under review by the U.S. Food and Drug Administration, involves adding functional copies of a modified form of the beta-globin gene into a patient’s own hematopoietic stem cells. Once those cells are reinfused, patients may produce adult hemoglobin at levels that eliminate the need for transfusions, according to Dr. Thompson.

At the meeting, Dr. Thompson reported on patients from two phase 1/2 and two phase 3 beti-cel clinical trials who subsequently enrolled in LTF-303, a 13-year follow-up study of the gene therapy’s safety and efficacy.

A total of 57 patients were included in this report, making it the largest gene therapy program to date in any blood disorder, according to Dr. Thompson. Before receiving beti-cel, the patients, who had a broad range of thalassemia genotypes, were receiving between 10 and almost 40 red blood cell transfusions per year, she reported.

Patients ranged in age from 5 to 35 years. The median age in the phase 1/2 studies was 20 years, while in the phase 3 studies it was 15 years.

“The early experience in the phase 1/2 trials allowed us to be more comfortable with enrolling more children, and that has actually helped us to understand safety and efficacy and children in the phase 3 setting,” Dr. Thompson said.

Fertility preservation measures had been undertaken by about 59% of patients from the phase 1/2 studies and 71% of patients from the phase 3 studies, the data show.

Among patients from the phase 3 beti-cel studies who could be evaluated, 31 out of 35 (or 89%) achieved durable transfusion independence, according to the investigator.

The median duration of ongoing transfusion independence was 32 months, with a range of about 18 to 49 months, she added.

Dr. Thompson also reported a subanalysis intended to assess iron status in 16 patients who restarted and then stopped chelation. That subanalysis demonstrated iron reduction in response to chelation, and then stabilization of iron markers after chelation was stopped. Post-gene therapy chelation led to reductions in liver iron concentration and serum ferritin that remained relatively stable after chelation was stopped, she said.

Serious adverse events occurred in eight patients in the long-term follow-up study. However, adverse events related to beti-cel have been absent beyond 2 years post-infusion, according to Dr. Thompson, who added that there have been no reported cases of replication-competent lentivirus, no clonal expansion, no insertional oncogenesis, and no malignancies observed.

“Very reassuringly, there have been 2 male patients, one of whom underwent fertility preservation, who report having healthy children with their partners,” she added.

Dr. Thompson provided disclosures related to Baxalta, Biomarin, bluebird bio, Inc., Celgene/BMS, CRISPR Therapeutics, Vertex, Editas, Graphite Bio, Novartis, Agios, Beam, and Global Blood Therapeutics.
 

In patients with transfusion-dependent beta-thalassemia, a single gene therapy infusion is capable of yielding durable transfusion independence and substantial improvements in iron overload, an investigator reported at the annual meeting of the American Society of Hematology.

Among patients who received betibeglogene autotemcel (beti-cel) in a phase 3 trial and enrolled in a long-term follow-up study, nearly 90% achieved durable transfusion independence, according to Alexis A. Thompson, MD, MPH, of the hematology section at the Ann & Robert H. Lurie Children’s Hospital of Chicago.

The median duration of ongoing transfusion independence was nearly 3 years as of this report, which Dr. Thompson described in a press conference at the meeting.

In a subanalysis of this international study, Dr. Thompson and co-investigators reported that in patients who achieve transfusion independence, chelation reduced iron, and iron markers stabilized even after chelation was stopped.

Beyond 2 years post-infusion, no adverse events related to the drug product were seen. This suggested that the therapy has a favorable long-term safety profile, according to Dr. Thompson.

“At this point, we believe that beti-cel is potentially curative for patients with TDT [transfusion-dependent beta-thalassemia],” Dr. Thompson said in the press conference.

This study answers one of the major outstanding questions about beti-cel and iron metabolism, according to Arielle L. Langer, MD, MPH, an instructor in medicine at Harvard Medical School and attending physician for adult thalassemia patients at Brigham and Women’s and Dana Farber Cancer Institute, both in Boston.

“Seeing the restoration of iron metabolism, it really takes us a step closer to really thinking the term ‘cure’ might truly apply,” Dr. Langer said in an interview.

Dr. Langer said she looks forward to “very long-term outcomes” of beti-cel-treated patients to see whether endocrinopathies and other long-term sequelae of TDT are also abated.

“This [study] is a great intermediate point, but really, when we think about how thalassemia harms and kills our patients, we really sometimes measure that in decades,” she said.

Beta-thalassemia is caused by mutations in the beta-globin gene, resulting in reduced levels of hemoglobin. Patients with TDT, the most serious form of the disease, have severe anemia and are often dependent on red blood cell transfusions from infancy onward, Dr. Thompson said.

With chronic transfusions needed to maintain hemoglobin levels, TDT patients inevitably experience iron overload, which can lead to organ damage and can be fatal. Consequently, patients will require lifelong iron chelation therapy, she added.

Beti-cel, an investigational ex vivo gene addition therapy currently under review by the U.S. Food and Drug Administration, involves adding functional copies of a modified form of the beta-globin gene into a patient’s own hematopoietic stem cells. Once those cells are reinfused, patients may produce adult hemoglobin at levels that eliminate the need for transfusions, according to Dr. Thompson.

At the meeting, Dr. Thompson reported on patients from two phase 1/2 and two phase 3 beti-cel clinical trials who subsequently enrolled in LTF-303, a 13-year follow-up study of the gene therapy’s safety and efficacy.

A total of 57 patients were included in this report, making it the largest gene therapy program to date in any blood disorder, according to Dr. Thompson. Before receiving beti-cel, the patients, who had a broad range of thalassemia genotypes, were receiving between 10 and almost 40 red blood cell transfusions per year, she reported.

Patients ranged in age from 5 to 35 years. The median age in the phase 1/2 studies was 20 years, while in the phase 3 studies it was 15 years.

“The early experience in the phase 1/2 trials allowed us to be more comfortable with enrolling more children, and that has actually helped us to understand safety and efficacy and children in the phase 3 setting,” Dr. Thompson said.

Fertility preservation measures had been undertaken by about 59% of patients from the phase 1/2 studies and 71% of patients from the phase 3 studies, the data show.

Among patients from the phase 3 beti-cel studies who could be evaluated, 31 out of 35 (or 89%) achieved durable transfusion independence, according to the investigator.

The median duration of ongoing transfusion independence was 32 months, with a range of about 18 to 49 months, she added.

Dr. Thompson also reported a subanalysis intended to assess iron status in 16 patients who restarted and then stopped chelation. That subanalysis demonstrated iron reduction in response to chelation, and then stabilization of iron markers after chelation was stopped. Post-gene therapy chelation led to reductions in liver iron concentration and serum ferritin that remained relatively stable after chelation was stopped, she said.

Serious adverse events occurred in eight patients in the long-term follow-up study. However, adverse events related to beti-cel have been absent beyond 2 years post-infusion, according to Dr. Thompson, who added that there have been no reported cases of replication-competent lentivirus, no clonal expansion, no insertional oncogenesis, and no malignancies observed.

“Very reassuringly, there have been 2 male patients, one of whom underwent fertility preservation, who report having healthy children with their partners,” she added.

Dr. Thompson provided disclosures related to Baxalta, Biomarin, bluebird bio, Inc., Celgene/BMS, CRISPR Therapeutics, Vertex, Editas, Graphite Bio, Novartis, Agios, Beam, and Global Blood Therapeutics.
 

ATLANTA — Chimeric antigen receptor (CAR) T-cell therapy has the potential to replace chemoimmunotherapy for second-line treatment of patients with large B-cell lymphoma (LBCL) that have relapsed or are refractory to first-line therapy, results of the phase 3 ZUMA-7 and TRANSFORM trials suggest.

Meletios Verras/Shutterstock

In the ZUMA-7 trial, at a median follow-up of 24.9 months, patients randomly assigned to receive CAR T-cell therapy with axicabtagene ciloleucel, or axi-cell (Yescarta) had a median event-free survival (EFS) of 8.3 months, compared with 2 months for patients randomly assigned to standard-of-care chemoimmunotherapy, reported Frederick L. Locke, MD, from the Moffitt Cancer Center in Tampa, Fla.

In TRANSFORM, comparing the CAR T construct lisocabtagene maraleucel, or liso-cel (Breyanzi) with standard-of-care second-line chemotherapy, median EFS was 10.1 months with liso-cel, compared with 2.3 months with standard of care, reported Manali Kamdar, MD, from the University of Colorado Cancer Center in Aurora.

The trials differed slightly in eligibility criteria and other details, but their overall results show great promise for improving second-line therapy for patients with relapsed or refractory LBCL, commented Laurie Sehn, MD, MPH, from the BC Cancer Centre for Lymphoid Cancer in Vancouver, Canada.

“It’s really remarkable that the results are so far in favor of the CAR T-cell therapy that I think it’s inevitable that this will become the standard of care,” Dr. Sehn commented. She was not an investigator in either of the two trials.

Dr. Sehn was speaking at a press briefing here during the annual meeting of the American Society of Hematology. The new data from the two studies were presented at oral sessions, and the results from ZUMA-7 were also simultaneously published in the New England Journal of Medicine.

“For somebody who treats patients with large B-cell lymphoma like I do, it’s incredibly frustrating when patients fail frontline therapy,” Dr. Sehn said. “We come into the second line with more chemotherapy and at higher doses to try and slam things down hard. Particularly for the patients who were enrolled in these studies, which were the worst of the worst — the patients who are either refractory to chemotherapy or relapsed relatively early, within 1 year — it’s not surprising that coming in with a novel approach and a cellular therapy that has a proven curative capacity may have outperformed coming in with more chemotherapy.”

In an interview with this news organization, Dr. Locke said that, based on the findings of the ZUMA-7 trial that he presented, it’s likely that chemotherapy in the second-line setting for relapsed/refractory LBCL will largely fall by the wayside.

The first question is to identify the patients who can tolerate CAR T-cell therapy. “We need to refer these patients to a CAR T-cell center to make that decision. That decision really can’t be made in the local oncologist’s office,” he said. “That being said, there are patients who need urgent therapy, and they may need to get second-line chemotherapy right away.”

“What we know with CAR T cells is that older patients and patients with comorbidities can get these therapies safely, so to me there is no obvious patient who can’t get CAR T-cell therapy,” he added.

Also at the briefing, Dr. Kamdar, who presented the TRANSFORM trial results, remarked that “in my opinion, this is a breakthrough therapy, which has shown superiority over standard of care, in terms of not just efficacy but also an extremely favorable safety profile,” she said at a briefing.   

For patients with LBCL for whom first-line therapy has failed, chemoimmunotherapy followed by high-dose chemotherapy and autologous stem cell transplant (ASCT) has been the standard of care, but only about 25% of patients who are candidates for ASCT achieve durable remissions, Dr. Kamdar noted.

Both ZUMA-7 and TRANSFORM were designed to test whether moving CAR T-cell therapy forward into the second line could improve outcomes.

ZUMA-7 results

THE ZUMA-7 trial randomly assigned 180 patients to receive CAR T-cell therapy with axi-cell and 179 patients to standard of care. This consisted of two or three cycles of investigator-selected, protocol-defined chemoimmunotherapy, with patients who had a complete or partial response going onto ASCT.

As noted, the primary endpoint of EFS according to blinded central review favored axi-cel, with 24-month event-free survival rates of 41% vs. 16% for standard of care. The difference translated into a hazard ratio (HR) for progression or death of 0.40 (P < .001).

In all, 65% of patients had a complete response (CR) to axi-cel, compared with 32% with standard of care. The respective overall response rates were 83% and 50% (P < .001).

Dr. Locke pointed out that 94% of the patients assigned to axi-cel received definitive therapy, compared with the 36% of patients in the standard-of-care arm who went on to ASCT.

In an interim analysis, 2-year estimated overall survival was 61% with axi-cel vs. 52% with standard of care, although this difference was not statistically significant.

Median overall survival was not reached with axi-cel, compared with 35.1 months with standard-of-care.

Grade 3 or higher adverse events occurred in 91% of patients with CAR T, and 83% with the standard of care. In the axi-cel arm, 6% of patients had grade 3 or higher cytokine release syndrome (CRS), and 21% had grade 3 or higher neurologic events, although there were no deaths related to CRS or neurologic events.

TRANSFORM results

The TRANSFORM trial had broader eligibility criteria than ZUMA-7, including patients who had diffuse LBCL not otherwise specified (de novo or transformed from indolent NHL), high-grade BCL (double- or triple-hit) with DLBCL histology, follicular lymphoma grade 3B, primary mediastinal LBCL, or T-cell/histocyte-rich LBCL.

A total of 184 patients were randomly assigned, 92 in each group, to receive either liso-cel or standard-of-care. Patients assigned to liso-cel were allowed to have bridging therapy, and crossover to liso-cel was allowed for patients assigned to standard of care who either did not have a response by week 9 after randomization, had disease progression at any time, or started a new antineoplastic therapy after ASCT.

As noted before, the primary endpoint of EFS significantly favored CAR T-cell therapy, with a hazard ratio of 0.349 (P < .0001).

The EFS rates at 6 months were 63.3% with liso-cel vs 33.4% with standard of care, and the EFS rates at 12 months were 44.5% vs. 23.7%, respectively.

“Overall survival data were still immature at the time of this analysis, but show a trend favoring liso-cel, despite crossover,” Dr. Kamdar said.

Grade 3 or higher adverse events (AEs) occurred in 92% of patients on liso-cell and 87% of patients on standard of care. There was one treatment-related death in the liso-cel arm, and two in the standard of care arm, both from grade 3 or higher AEs. Neutropenia, anemia, and thrombocytopenia were the most common treatment-emergent AEs in each group.

ZUMA-7 is supported by Kite. Dr. Locke disclosed serving as a scientific advisor to Kite and relationships with other companies. TRANSFORM is supported by Celgene (BMS). Dr. Kamdar disclosed consultancy fees from BMS and others.


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

ATLANTA — Chimeric antigen receptor (CAR) T-cell therapy has the potential to replace chemoimmunotherapy for second-line treatment of patients with large B-cell lymphoma (LBCL) that have relapsed or are refractory to first-line therapy, results of the phase 3 ZUMA-7 and TRANSFORM trials suggest.

Meletios Verras/Shutterstock

In the ZUMA-7 trial, at a median follow-up of 24.9 months, patients randomly assigned to receive CAR T-cell therapy with axicabtagene ciloleucel, or axi-cell (Yescarta) had a median event-free survival (EFS) of 8.3 months, compared with 2 months for patients randomly assigned to standard-of-care chemoimmunotherapy, reported Frederick L. Locke, MD, from the Moffitt Cancer Center in Tampa, Fla.

In TRANSFORM, comparing the CAR T construct lisocabtagene maraleucel, or liso-cel (Breyanzi) with standard-of-care second-line chemotherapy, median EFS was 10.1 months with liso-cel, compared with 2.3 months with standard of care, reported Manali Kamdar, MD, from the University of Colorado Cancer Center in Aurora.

The trials differed slightly in eligibility criteria and other details, but their overall results show great promise for improving second-line therapy for patients with relapsed or refractory LBCL, commented Laurie Sehn, MD, MPH, from the BC Cancer Centre for Lymphoid Cancer in Vancouver, Canada.

“It’s really remarkable that the results are so far in favor of the CAR T-cell therapy that I think it’s inevitable that this will become the standard of care,” Dr. Sehn commented. She was not an investigator in either of the two trials.

Dr. Sehn was speaking at a press briefing here during the annual meeting of the American Society of Hematology. The new data from the two studies were presented at oral sessions, and the results from ZUMA-7 were also simultaneously published in the New England Journal of Medicine.

“For somebody who treats patients with large B-cell lymphoma like I do, it’s incredibly frustrating when patients fail frontline therapy,” Dr. Sehn said. “We come into the second line with more chemotherapy and at higher doses to try and slam things down hard. Particularly for the patients who were enrolled in these studies, which were the worst of the worst — the patients who are either refractory to chemotherapy or relapsed relatively early, within 1 year — it’s not surprising that coming in with a novel approach and a cellular therapy that has a proven curative capacity may have outperformed coming in with more chemotherapy.”

In an interview with this news organization, Dr. Locke said that, based on the findings of the ZUMA-7 trial that he presented, it’s likely that chemotherapy in the second-line setting for relapsed/refractory LBCL will largely fall by the wayside.

The first question is to identify the patients who can tolerate CAR T-cell therapy. “We need to refer these patients to a CAR T-cell center to make that decision. That decision really can’t be made in the local oncologist’s office,” he said. “That being said, there are patients who need urgent therapy, and they may need to get second-line chemotherapy right away.”

“What we know with CAR T cells is that older patients and patients with comorbidities can get these therapies safely, so to me there is no obvious patient who can’t get CAR T-cell therapy,” he added.

Also at the briefing, Dr. Kamdar, who presented the TRANSFORM trial results, remarked that “in my opinion, this is a breakthrough therapy, which has shown superiority over standard of care, in terms of not just efficacy but also an extremely favorable safety profile,” she said at a briefing.   

For patients with LBCL for whom first-line therapy has failed, chemoimmunotherapy followed by high-dose chemotherapy and autologous stem cell transplant (ASCT) has been the standard of care, but only about 25% of patients who are candidates for ASCT achieve durable remissions, Dr. Kamdar noted.

Both ZUMA-7 and TRANSFORM were designed to test whether moving CAR T-cell therapy forward into the second line could improve outcomes.

ZUMA-7 results

THE ZUMA-7 trial randomly assigned 180 patients to receive CAR T-cell therapy with axi-cell and 179 patients to standard of care. This consisted of two or three cycles of investigator-selected, protocol-defined chemoimmunotherapy, with patients who had a complete or partial response going onto ASCT.

As noted, the primary endpoint of EFS according to blinded central review favored axi-cel, with 24-month event-free survival rates of 41% vs. 16% for standard of care. The difference translated into a hazard ratio (HR) for progression or death of 0.40 (P < .001).

In all, 65% of patients had a complete response (CR) to axi-cel, compared with 32% with standard of care. The respective overall response rates were 83% and 50% (P < .001).

Dr. Locke pointed out that 94% of the patients assigned to axi-cel received definitive therapy, compared with the 36% of patients in the standard-of-care arm who went on to ASCT.

In an interim analysis, 2-year estimated overall survival was 61% with axi-cel vs. 52% with standard of care, although this difference was not statistically significant.

Median overall survival was not reached with axi-cel, compared with 35.1 months with standard-of-care.

Grade 3 or higher adverse events occurred in 91% of patients with CAR T, and 83% with the standard of care. In the axi-cel arm, 6% of patients had grade 3 or higher cytokine release syndrome (CRS), and 21% had grade 3 or higher neurologic events, although there were no deaths related to CRS or neurologic events.

TRANSFORM results

The TRANSFORM trial had broader eligibility criteria than ZUMA-7, including patients who had diffuse LBCL not otherwise specified (de novo or transformed from indolent NHL), high-grade BCL (double- or triple-hit) with DLBCL histology, follicular lymphoma grade 3B, primary mediastinal LBCL, or T-cell/histocyte-rich LBCL.

A total of 184 patients were randomly assigned, 92 in each group, to receive either liso-cel or standard-of-care. Patients assigned to liso-cel were allowed to have bridging therapy, and crossover to liso-cel was allowed for patients assigned to standard of care who either did not have a response by week 9 after randomization, had disease progression at any time, or started a new antineoplastic therapy after ASCT.

As noted before, the primary endpoint of EFS significantly favored CAR T-cell therapy, with a hazard ratio of 0.349 (P < .0001).

The EFS rates at 6 months were 63.3% with liso-cel vs 33.4% with standard of care, and the EFS rates at 12 months were 44.5% vs. 23.7%, respectively.

“Overall survival data were still immature at the time of this analysis, but show a trend favoring liso-cel, despite crossover,” Dr. Kamdar said.

Grade 3 or higher adverse events (AEs) occurred in 92% of patients on liso-cell and 87% of patients on standard of care. There was one treatment-related death in the liso-cel arm, and two in the standard of care arm, both from grade 3 or higher AEs. Neutropenia, anemia, and thrombocytopenia were the most common treatment-emergent AEs in each group.

ZUMA-7 is supported by Kite. Dr. Locke disclosed serving as a scientific advisor to Kite and relationships with other companies. TRANSFORM is supported by Celgene (BMS). Dr. Kamdar disclosed consultancy fees from BMS and others.


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

ATLANTA — Chimeric antigen receptor (CAR) T-cell therapy has the potential to replace chemoimmunotherapy for second-line treatment of patients with large B-cell lymphoma (LBCL) that have relapsed or are refractory to first-line therapy, results of the phase 3 ZUMA-7 and TRANSFORM trials suggest.

Meletios Verras/Shutterstock

In the ZUMA-7 trial, at a median follow-up of 24.9 months, patients randomly assigned to receive CAR T-cell therapy with axicabtagene ciloleucel, or axi-cell (Yescarta) had a median event-free survival (EFS) of 8.3 months, compared with 2 months for patients randomly assigned to standard-of-care chemoimmunotherapy, reported Frederick L. Locke, MD, from the Moffitt Cancer Center in Tampa, Fla.

In TRANSFORM, comparing the CAR T construct lisocabtagene maraleucel, or liso-cel (Breyanzi) with standard-of-care second-line chemotherapy, median EFS was 10.1 months with liso-cel, compared with 2.3 months with standard of care, reported Manali Kamdar, MD, from the University of Colorado Cancer Center in Aurora.

The trials differed slightly in eligibility criteria and other details, but their overall results show great promise for improving second-line therapy for patients with relapsed or refractory LBCL, commented Laurie Sehn, MD, MPH, from the BC Cancer Centre for Lymphoid Cancer in Vancouver, Canada.

“It’s really remarkable that the results are so far in favor of the CAR T-cell therapy that I think it’s inevitable that this will become the standard of care,” Dr. Sehn commented. She was not an investigator in either of the two trials.

Dr. Sehn was speaking at a press briefing here during the annual meeting of the American Society of Hematology. The new data from the two studies were presented at oral sessions, and the results from ZUMA-7 were also simultaneously published in the New England Journal of Medicine.

“For somebody who treats patients with large B-cell lymphoma like I do, it’s incredibly frustrating when patients fail frontline therapy,” Dr. Sehn said. “We come into the second line with more chemotherapy and at higher doses to try and slam things down hard. Particularly for the patients who were enrolled in these studies, which were the worst of the worst — the patients who are either refractory to chemotherapy or relapsed relatively early, within 1 year — it’s not surprising that coming in with a novel approach and a cellular therapy that has a proven curative capacity may have outperformed coming in with more chemotherapy.”

In an interview with this news organization, Dr. Locke said that, based on the findings of the ZUMA-7 trial that he presented, it’s likely that chemotherapy in the second-line setting for relapsed/refractory LBCL will largely fall by the wayside.

The first question is to identify the patients who can tolerate CAR T-cell therapy. “We need to refer these patients to a CAR T-cell center to make that decision. That decision really can’t be made in the local oncologist’s office,” he said. “That being said, there are patients who need urgent therapy, and they may need to get second-line chemotherapy right away.”

“What we know with CAR T cells is that older patients and patients with comorbidities can get these therapies safely, so to me there is no obvious patient who can’t get CAR T-cell therapy,” he added.

Also at the briefing, Dr. Kamdar, who presented the TRANSFORM trial results, remarked that “in my opinion, this is a breakthrough therapy, which has shown superiority over standard of care, in terms of not just efficacy but also an extremely favorable safety profile,” she said at a briefing.   

For patients with LBCL for whom first-line therapy has failed, chemoimmunotherapy followed by high-dose chemotherapy and autologous stem cell transplant (ASCT) has been the standard of care, but only about 25% of patients who are candidates for ASCT achieve durable remissions, Dr. Kamdar noted.

Both ZUMA-7 and TRANSFORM were designed to test whether moving CAR T-cell therapy forward into the second line could improve outcomes.

ZUMA-7 results

THE ZUMA-7 trial randomly assigned 180 patients to receive CAR T-cell therapy with axi-cell and 179 patients to standard of care. This consisted of two or three cycles of investigator-selected, protocol-defined chemoimmunotherapy, with patients who had a complete or partial response going onto ASCT.

As noted, the primary endpoint of EFS according to blinded central review favored axi-cel, with 24-month event-free survival rates of 41% vs. 16% for standard of care. The difference translated into a hazard ratio (HR) for progression or death of 0.40 (P < .001).

In all, 65% of patients had a complete response (CR) to axi-cel, compared with 32% with standard of care. The respective overall response rates were 83% and 50% (P < .001).

Dr. Locke pointed out that 94% of the patients assigned to axi-cel received definitive therapy, compared with the 36% of patients in the standard-of-care arm who went on to ASCT.

In an interim analysis, 2-year estimated overall survival was 61% with axi-cel vs. 52% with standard of care, although this difference was not statistically significant.

Median overall survival was not reached with axi-cel, compared with 35.1 months with standard-of-care.

Grade 3 or higher adverse events occurred in 91% of patients with CAR T, and 83% with the standard of care. In the axi-cel arm, 6% of patients had grade 3 or higher cytokine release syndrome (CRS), and 21% had grade 3 or higher neurologic events, although there were no deaths related to CRS or neurologic events.

TRANSFORM results

The TRANSFORM trial had broader eligibility criteria than ZUMA-7, including patients who had diffuse LBCL not otherwise specified (de novo or transformed from indolent NHL), high-grade BCL (double- or triple-hit) with DLBCL histology, follicular lymphoma grade 3B, primary mediastinal LBCL, or T-cell/histocyte-rich LBCL.

A total of 184 patients were randomly assigned, 92 in each group, to receive either liso-cel or standard-of-care. Patients assigned to liso-cel were allowed to have bridging therapy, and crossover to liso-cel was allowed for patients assigned to standard of care who either did not have a response by week 9 after randomization, had disease progression at any time, or started a new antineoplastic therapy after ASCT.

As noted before, the primary endpoint of EFS significantly favored CAR T-cell therapy, with a hazard ratio of 0.349 (P < .0001).

The EFS rates at 6 months were 63.3% with liso-cel vs 33.4% with standard of care, and the EFS rates at 12 months were 44.5% vs. 23.7%, respectively.

“Overall survival data were still immature at the time of this analysis, but show a trend favoring liso-cel, despite crossover,” Dr. Kamdar said.

Grade 3 or higher adverse events (AEs) occurred in 92% of patients on liso-cell and 87% of patients on standard of care. There was one treatment-related death in the liso-cel arm, and two in the standard of care arm, both from grade 3 or higher AEs. Neutropenia, anemia, and thrombocytopenia were the most common treatment-emergent AEs in each group.

ZUMA-7 is supported by Kite. Dr. Locke disclosed serving as a scientific advisor to Kite and relationships with other companies. TRANSFORM is supported by Celgene (BMS). Dr. Kamdar disclosed consultancy fees from BMS and others.


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

In 2021, the American Society of Hematology will be hosting its annual meeting in a hybrid format. Content will be presented both live and in person at the Georgia World Congress Center in Atlanta and also online for those who can’t or don’t want to be there in person.

Inevitably during the ongoing pandemic, the meeting will contain key sessions on COVID-19 in hematology, including a plenary presentation outlining a biologic mechanism for the increased coagulopathy with SARS-CoV-2 infections.

In addition, there will be a scientific symposium on COVID-19 vaccination in immunocompromised patients and a special moderated session summarizing nine abstracts on the science of thrombosis in COVID-19, outcomes in patients with hematologic disease, and vaccine responses.

And speaking of COVID, lest anyone forget, annual meeting attendees will be required to be fully vaccinated and masked. Free COVID-19 testing will be available at stations situated throughout the convention center.
 

Diversifying care

A glimpse of some of the most exciting research to be presented at ASH 2021 was given at a premeeting press briefing by Mikkael A. Sekeres, MD, chair of the ASH committee on communications and chief of the division of hematology at the Sylvester Comprehensive Cancer Center at the University of Miami.

For example, investigators at Massachusetts General Hospital in Boston will present new data on code-status transitions among patients with poor-prognosis high-risk acute myeloid leukemia (AML) who are approaching the end of life. Their findings suggest that physician-patient discussions about the goals of care may occur too late in the course of illness for many patients (abstract 109).

“While there have been many advances in the treatment of acute myeloid leukemia, and in fact there has been significant progress even among high-risk patients, addressing end-of-life issues is an often neglected area,” commented briefing participant Martin A. Tallman, MD, from Memorial Sloan Kettering Cancer Center, New York, who is also the current ASH president.

On a more upbeat note, Dr. Tallman also pointed to the results of the phase 3, randomized AGILE trial as an example of progress in AML, especially for patients with newly diagnosed high-risk disease who have mutations in IDH1. This trial investigated a new approach to treatment, with a combination of the combination of the IDH1 inhibitor ivosidenib (Tibsovo) and azacitidine, and compared it with azacitidine alone. The investigators assessed impact on event-free survival, overall survival, and clinical responses (abstract 697).

Dr. Tallman also highlighted abstracts touching on racial, social, and socioeconomic contributors to health care disparities among children with acute lymphoblastic leukemia (ALL; abstract 211) and on clinical trial enrollment characteristics and outcomes for Black and Hispanic adolescents and young adults with ALL (abstract 337).
 

Immunotherapy advances

Some of the most eagerly awaited abstracts will be highlighting advances in immunotherapy for hematologic malignancies, and these were previewed by Cynthia E. Dunbar, MD, ASH secretary and chief of the Translational Stem Cell Biology Branch within the Intramural Research Program of the National Heart, Lung, and Blood Institute in Bethesda, Md.

These abstracts include the primary analysis of the ZUMA-7 trial, a randomized, phase 3 study comparing the chimeric antigen receptor T-cell (CAR T) construct axicabtagene ciloleucel (axi-cel; Yescarta) with standard of care in patients with relapsed or refractory large B-cell lymphomas (LBCLs; abstract 2) and the interim analysis of the randomized, phase 3 Transform Study comparing the CAR T construct lisocabtagene maralecleucl (liso-cel; Breyanzi) with salvage chemotherapy in patients with relapsed/refractory LBCL (abstract 91).

“Over 500 patients were enrolled in the two studies, and both abstracts report significantly longer survival without relapse in the CAR T arm – for instance, fourfold higher in ZUMA-7, compared to standard of care,” Dr. Dunbar said at the briefing.

“These abstracts provide really critical information to patients, their treating physicians, and the payers who are trying to decide whether use of these expensive, complex, and potentially toxic CAR T-cell therapies are justified, compared to standard therapy,” she said.

Dr. Dunbar also highlighted an abstract on the addition of the anti-CD38 monoclonal antibody isatuximab (Sarclisa) to lenalidomide, bortezomib, and dexamethasone as induction therapy for patients with newly diagnosed multiple myeloma who are eligible for stem cell transplantation (abstract 463).

“The authors report that patients on the isatuximab arm had significantly fewer tumor cells following treatment,” Dr. Dunbar said. “We have come a long way beyond treating myeloma with a single drug, with remissions now measured in many years instead of 1 or 2 following initiation of treatment, and this abstract is another demonstration that novel combinations of multiple agents are really making a difference in this very debilitating disease.”

She also cited an abstract (abstract 127) on monotherapy with the novel bispecific T-cell–engaging monoclonal antibody mosunetuzumab for treatment of patients with follicular lymphoma that has relapsed or is refractory to at least two prior lines of therapy.
 

Old disorders, new insights

Other abstracts highlighted at the premeeting press briefing included a study that found a high prevalence of monoclonal gammopathy in persons at risk for multiple myeloma (abstract 152) and another with the surprising finding that clonal hematopoiesis, a risk factor myeloid malignancies, may be protective against Alzheimer’s disease (abstract 5).

In addition, a long-term follow-up study of patients with transfusion-dependent beta-thalassemia treated with gene therapy showed that some patients have become transfusion independent and iron homeostasis was restored (abstract 573).
 

Presentations from CDC and FDA

Dr. Sekeres highlighted other events of interest scheduled for ASH 2021, including a Grassroots Network Lunch featuring a discussion with Rochelle Walensky, MD, MPH, director of the Centers for Disease Control and Prevention in Atlanta, and a joint symposium between ASH and the Food and Drug Administration on newly approved drugs in hematology.

Dr. Sekeres has disclosed consulting/advising for Novartis, Takea/Millennium, and Bristol-Myers Squibb. Dr. Dunbar reported no relevant conflicts of interest. Dr. Tallman disclosed consulting/advising with and research funding from multiple entities.

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

In 2021, the American Society of Hematology will be hosting its annual meeting in a hybrid format. Content will be presented both live and in person at the Georgia World Congress Center in Atlanta and also online for those who can’t or don’t want to be there in person.

Inevitably during the ongoing pandemic, the meeting will contain key sessions on COVID-19 in hematology, including a plenary presentation outlining a biologic mechanism for the increased coagulopathy with SARS-CoV-2 infections.

In addition, there will be a scientific symposium on COVID-19 vaccination in immunocompromised patients and a special moderated session summarizing nine abstracts on the science of thrombosis in COVID-19, outcomes in patients with hematologic disease, and vaccine responses.

And speaking of COVID, lest anyone forget, annual meeting attendees will be required to be fully vaccinated and masked. Free COVID-19 testing will be available at stations situated throughout the convention center.
 

Diversifying care

A glimpse of some of the most exciting research to be presented at ASH 2021 was given at a premeeting press briefing by Mikkael A. Sekeres, MD, chair of the ASH committee on communications and chief of the division of hematology at the Sylvester Comprehensive Cancer Center at the University of Miami.

For example, investigators at Massachusetts General Hospital in Boston will present new data on code-status transitions among patients with poor-prognosis high-risk acute myeloid leukemia (AML) who are approaching the end of life. Their findings suggest that physician-patient discussions about the goals of care may occur too late in the course of illness for many patients (abstract 109).

“While there have been many advances in the treatment of acute myeloid leukemia, and in fact there has been significant progress even among high-risk patients, addressing end-of-life issues is an often neglected area,” commented briefing participant Martin A. Tallman, MD, from Memorial Sloan Kettering Cancer Center, New York, who is also the current ASH president.

On a more upbeat note, Dr. Tallman also pointed to the results of the phase 3, randomized AGILE trial as an example of progress in AML, especially for patients with newly diagnosed high-risk disease who have mutations in IDH1. This trial investigated a new approach to treatment, with a combination of the combination of the IDH1 inhibitor ivosidenib (Tibsovo) and azacitidine, and compared it with azacitidine alone. The investigators assessed impact on event-free survival, overall survival, and clinical responses (abstract 697).

Dr. Tallman also highlighted abstracts touching on racial, social, and socioeconomic contributors to health care disparities among children with acute lymphoblastic leukemia (ALL; abstract 211) and on clinical trial enrollment characteristics and outcomes for Black and Hispanic adolescents and young adults with ALL (abstract 337).
 

Immunotherapy advances

Some of the most eagerly awaited abstracts will be highlighting advances in immunotherapy for hematologic malignancies, and these were previewed by Cynthia E. Dunbar, MD, ASH secretary and chief of the Translational Stem Cell Biology Branch within the Intramural Research Program of the National Heart, Lung, and Blood Institute in Bethesda, Md.

These abstracts include the primary analysis of the ZUMA-7 trial, a randomized, phase 3 study comparing the chimeric antigen receptor T-cell (CAR T) construct axicabtagene ciloleucel (axi-cel; Yescarta) with standard of care in patients with relapsed or refractory large B-cell lymphomas (LBCLs; abstract 2) and the interim analysis of the randomized, phase 3 Transform Study comparing the CAR T construct lisocabtagene maralecleucl (liso-cel; Breyanzi) with salvage chemotherapy in patients with relapsed/refractory LBCL (abstract 91).

“Over 500 patients were enrolled in the two studies, and both abstracts report significantly longer survival without relapse in the CAR T arm – for instance, fourfold higher in ZUMA-7, compared to standard of care,” Dr. Dunbar said at the briefing.

“These abstracts provide really critical information to patients, their treating physicians, and the payers who are trying to decide whether use of these expensive, complex, and potentially toxic CAR T-cell therapies are justified, compared to standard therapy,” she said.

Dr. Dunbar also highlighted an abstract on the addition of the anti-CD38 monoclonal antibody isatuximab (Sarclisa) to lenalidomide, bortezomib, and dexamethasone as induction therapy for patients with newly diagnosed multiple myeloma who are eligible for stem cell transplantation (abstract 463).

“The authors report that patients on the isatuximab arm had significantly fewer tumor cells following treatment,” Dr. Dunbar said. “We have come a long way beyond treating myeloma with a single drug, with remissions now measured in many years instead of 1 or 2 following initiation of treatment, and this abstract is another demonstration that novel combinations of multiple agents are really making a difference in this very debilitating disease.”

She also cited an abstract (abstract 127) on monotherapy with the novel bispecific T-cell–engaging monoclonal antibody mosunetuzumab for treatment of patients with follicular lymphoma that has relapsed or is refractory to at least two prior lines of therapy.
 

Old disorders, new insights

Other abstracts highlighted at the premeeting press briefing included a study that found a high prevalence of monoclonal gammopathy in persons at risk for multiple myeloma (abstract 152) and another with the surprising finding that clonal hematopoiesis, a risk factor myeloid malignancies, may be protective against Alzheimer’s disease (abstract 5).

In addition, a long-term follow-up study of patients with transfusion-dependent beta-thalassemia treated with gene therapy showed that some patients have become transfusion independent and iron homeostasis was restored (abstract 573).
 

Presentations from CDC and FDA

Dr. Sekeres highlighted other events of interest scheduled for ASH 2021, including a Grassroots Network Lunch featuring a discussion with Rochelle Walensky, MD, MPH, director of the Centers for Disease Control and Prevention in Atlanta, and a joint symposium between ASH and the Food and Drug Administration on newly approved drugs in hematology.

Dr. Sekeres has disclosed consulting/advising for Novartis, Takea/Millennium, and Bristol-Myers Squibb. Dr. Dunbar reported no relevant conflicts of interest. Dr. Tallman disclosed consulting/advising with and research funding from multiple entities.

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

In 2021, the American Society of Hematology will be hosting its annual meeting in a hybrid format. Content will be presented both live and in person at the Georgia World Congress Center in Atlanta and also online for those who can’t or don’t want to be there in person.

Inevitably during the ongoing pandemic, the meeting will contain key sessions on COVID-19 in hematology, including a plenary presentation outlining a biologic mechanism for the increased coagulopathy with SARS-CoV-2 infections.

In addition, there will be a scientific symposium on COVID-19 vaccination in immunocompromised patients and a special moderated session summarizing nine abstracts on the science of thrombosis in COVID-19, outcomes in patients with hematologic disease, and vaccine responses.

And speaking of COVID, lest anyone forget, annual meeting attendees will be required to be fully vaccinated and masked. Free COVID-19 testing will be available at stations situated throughout the convention center.
 

Diversifying care

A glimpse of some of the most exciting research to be presented at ASH 2021 was given at a premeeting press briefing by Mikkael A. Sekeres, MD, chair of the ASH committee on communications and chief of the division of hematology at the Sylvester Comprehensive Cancer Center at the University of Miami.

For example, investigators at Massachusetts General Hospital in Boston will present new data on code-status transitions among patients with poor-prognosis high-risk acute myeloid leukemia (AML) who are approaching the end of life. Their findings suggest that physician-patient discussions about the goals of care may occur too late in the course of illness for many patients (abstract 109).

“While there have been many advances in the treatment of acute myeloid leukemia, and in fact there has been significant progress even among high-risk patients, addressing end-of-life issues is an often neglected area,” commented briefing participant Martin A. Tallman, MD, from Memorial Sloan Kettering Cancer Center, New York, who is also the current ASH president.

On a more upbeat note, Dr. Tallman also pointed to the results of the phase 3, randomized AGILE trial as an example of progress in AML, especially for patients with newly diagnosed high-risk disease who have mutations in IDH1. This trial investigated a new approach to treatment, with a combination of the combination of the IDH1 inhibitor ivosidenib (Tibsovo) and azacitidine, and compared it with azacitidine alone. The investigators assessed impact on event-free survival, overall survival, and clinical responses (abstract 697).

Dr. Tallman also highlighted abstracts touching on racial, social, and socioeconomic contributors to health care disparities among children with acute lymphoblastic leukemia (ALL; abstract 211) and on clinical trial enrollment characteristics and outcomes for Black and Hispanic adolescents and young adults with ALL (abstract 337).
 

Immunotherapy advances

Some of the most eagerly awaited abstracts will be highlighting advances in immunotherapy for hematologic malignancies, and these were previewed by Cynthia E. Dunbar, MD, ASH secretary and chief of the Translational Stem Cell Biology Branch within the Intramural Research Program of the National Heart, Lung, and Blood Institute in Bethesda, Md.

These abstracts include the primary analysis of the ZUMA-7 trial, a randomized, phase 3 study comparing the chimeric antigen receptor T-cell (CAR T) construct axicabtagene ciloleucel (axi-cel; Yescarta) with standard of care in patients with relapsed or refractory large B-cell lymphomas (LBCLs; abstract 2) and the interim analysis of the randomized, phase 3 Transform Study comparing the CAR T construct lisocabtagene maralecleucl (liso-cel; Breyanzi) with salvage chemotherapy in patients with relapsed/refractory LBCL (abstract 91).

“Over 500 patients were enrolled in the two studies, and both abstracts report significantly longer survival without relapse in the CAR T arm – for instance, fourfold higher in ZUMA-7, compared to standard of care,” Dr. Dunbar said at the briefing.

“These abstracts provide really critical information to patients, their treating physicians, and the payers who are trying to decide whether use of these expensive, complex, and potentially toxic CAR T-cell therapies are justified, compared to standard therapy,” she said.

Dr. Dunbar also highlighted an abstract on the addition of the anti-CD38 monoclonal antibody isatuximab (Sarclisa) to lenalidomide, bortezomib, and dexamethasone as induction therapy for patients with newly diagnosed multiple myeloma who are eligible for stem cell transplantation (abstract 463).

“The authors report that patients on the isatuximab arm had significantly fewer tumor cells following treatment,” Dr. Dunbar said. “We have come a long way beyond treating myeloma with a single drug, with remissions now measured in many years instead of 1 or 2 following initiation of treatment, and this abstract is another demonstration that novel combinations of multiple agents are really making a difference in this very debilitating disease.”

She also cited an abstract (abstract 127) on monotherapy with the novel bispecific T-cell–engaging monoclonal antibody mosunetuzumab for treatment of patients with follicular lymphoma that has relapsed or is refractory to at least two prior lines of therapy.
 

Old disorders, new insights

Other abstracts highlighted at the premeeting press briefing included a study that found a high prevalence of monoclonal gammopathy in persons at risk for multiple myeloma (abstract 152) and another with the surprising finding that clonal hematopoiesis, a risk factor myeloid malignancies, may be protective against Alzheimer’s disease (abstract 5).

In addition, a long-term follow-up study of patients with transfusion-dependent beta-thalassemia treated with gene therapy showed that some patients have become transfusion independent and iron homeostasis was restored (abstract 573).
 

Presentations from CDC and FDA

Dr. Sekeres highlighted other events of interest scheduled for ASH 2021, including a Grassroots Network Lunch featuring a discussion with Rochelle Walensky, MD, MPH, director of the Centers for Disease Control and Prevention in Atlanta, and a joint symposium between ASH and the Food and Drug Administration on newly approved drugs in hematology.

Dr. Sekeres has disclosed consulting/advising for Novartis, Takea/Millennium, and Bristol-Myers Squibb. Dr. Dunbar reported no relevant conflicts of interest. Dr. Tallman disclosed consulting/advising with and research funding from multiple entities.

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