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NHL: As a second-line treatment in phase 3 trial, tisa-cel disappoints
according to results of a randomized, phase 3 trial.
The chimeric antigen receptor (CAR) T-cell therapy did not improve event-free survival (EFS) in this phase 3 BELINDA study, potentially because of study design decisions or imbalances in relevant patient characteristics, according to the study investigators.
Despite the negative result, insights from this study will inform the development of future clinical trials of CAR T-cell therapy, said BELINDA investigator Michael R. Bishop, MD, of the David and Etta Jonas Center for Cellular Therapy, University of Chicago.
Findings of BELINDA, presented at the annual meeting of the American Society of Hematology, stand in contrast to two other high-profile CAR T-cell therapy studies also presented at the meeting. Those other studies demonstrated significant improvements in EFS in the second-line treatment of large B-cell lymphomas.
“All of us are excited to see that the other two trials were positive, and we were hoping that ours would be as well, but there are significant differences in the trial design,” Dr. Bishop said in a press conference held at the ASH meeting.
Tisagenlecleucel (tisa-cel), an anti-CD19 CAR T-cell therapy, is already approved by the Food and Drug Administration for the treatment of patients with relapsed or refractory large B-cell lymphomas after at least two other lines of systemic therapy.
The aim of the pivotal phase 3, randomized, multicenter BELINDA study was to evaluate tisa-cel earlier in the course of treatment for patients with more aggressive disease, according to Dr. Bishop.
About two-thirds of non-Hodgkin lymphoma patients will be cured with first-line treatment. However, very poor outcomes are seen among patients with disease that does not respond to the initial treatment or that reoccurs shortly afterward, Dr. Bishop said.
The standard of care approach for those patients is second-line therapy, he noted, usually with combination chemoimmunotherapy, followed by autologous stem cell transplant if the disease responds to chemotherapy.
“Unfortunately, only a minority of those patients will be found to have chemotherapy-sensitive disease and be able to go on to autologous stem cell transplantation,” Dr. Bishop said. “And even in that subgroup of patients, the outcomes are relatively poor.”
Accordingly, the phase 3 BELINDA study enrolled patients with aggressive non-Hodgkin lymphomas that either did not respond to first-line treatment or that reoccurred within 12 months.
The primary endpoint of the study was EFS, defined as the time from randomization to either stable or progressive disease at or after a week 12 assessment or to any-cause death at any time.
While that primary endpoint was not met for tisa-cel versus standard of care therapy, two other randomized, phase 3 studies presented at the ASH meeting did demonstrate that CAR T-cell therapy extended EFS when given as a second-line lymphoma treatment.
In the randomized, phase 3 ZUMA-7 trial, axicabtagene ciloleucel (axi-cel) significantly improved EFS versus standard of care in the treatment of patients with large B-cell lymphoma refractory to or relapsed within 12 months of adequate first-line therapy, according to investigators.
Similarly, the investigators said that treatment with lisocabtagene maraleucel (liso-cel) led to a significant improvement in EFS in TRANSFORM, a randomized, phase 3 clinical trial that enrolled patients with large B-cell lymphoma that was refractory to first-line therapy or else relapsed within 12 months of that treatment.
“It’s very possible that either or both the patient characteristics and the study design is what led to the difference in the top-line study results,” lymphoma specialist Andrew M. Evens, DO, said in an interview.
There were substantial differences between the studies in terms of what was allowed as optional bridging therapy and salvage therapy, according to Dr. Evens, associate director for clinical services and director of the lymphoma program at Rutgers Cancer Institute in New Brunswick, N.J.
“In ZUMA-7, they only allowed steroids as bridging therapy,” said Dr. Evens, who was not an investigator on any of the three second-line CAR T-cell studies.
In the BELINDA study, optional platinum-based chemotherapy bridging treatment allowed in one arm of the study could have potentially delayed tisa-cel infusion until after the week 6 assessment, study investigators reported in their ASH meeting abstract.
Differences in lymphodepleting therapy prior to CAR T-cell therapy could have also played a role. According to Dr. Bishop, the total doses of cyclophosphamide and fludarabine in BELINDA were 900 mg/m2 and 75 mg/m2, respectively, while in the other two trials, doses were 1,500 mg/m2 and 90 mg/m2, respectively.
Lymphodepleting chemotherapy is “extremely important” in the success of CAR T-cell therapeutic approaches, he noted at the press conference.
Dr. Bishop reported receiving consultancy fees from Arcellx, Autolus Therapeutics, Bristol-Myers Squibb, CRISPR, Kite/Gilead, and Novartis. He also reported research funding from Bristol-Myers Squibb and Kite/Gilead.
according to results of a randomized, phase 3 trial.
The chimeric antigen receptor (CAR) T-cell therapy did not improve event-free survival (EFS) in this phase 3 BELINDA study, potentially because of study design decisions or imbalances in relevant patient characteristics, according to the study investigators.
Despite the negative result, insights from this study will inform the development of future clinical trials of CAR T-cell therapy, said BELINDA investigator Michael R. Bishop, MD, of the David and Etta Jonas Center for Cellular Therapy, University of Chicago.
Findings of BELINDA, presented at the annual meeting of the American Society of Hematology, stand in contrast to two other high-profile CAR T-cell therapy studies also presented at the meeting. Those other studies demonstrated significant improvements in EFS in the second-line treatment of large B-cell lymphomas.
“All of us are excited to see that the other two trials were positive, and we were hoping that ours would be as well, but there are significant differences in the trial design,” Dr. Bishop said in a press conference held at the ASH meeting.
Tisagenlecleucel (tisa-cel), an anti-CD19 CAR T-cell therapy, is already approved by the Food and Drug Administration for the treatment of patients with relapsed or refractory large B-cell lymphomas after at least two other lines of systemic therapy.
The aim of the pivotal phase 3, randomized, multicenter BELINDA study was to evaluate tisa-cel earlier in the course of treatment for patients with more aggressive disease, according to Dr. Bishop.
About two-thirds of non-Hodgkin lymphoma patients will be cured with first-line treatment. However, very poor outcomes are seen among patients with disease that does not respond to the initial treatment or that reoccurs shortly afterward, Dr. Bishop said.
The standard of care approach for those patients is second-line therapy, he noted, usually with combination chemoimmunotherapy, followed by autologous stem cell transplant if the disease responds to chemotherapy.
“Unfortunately, only a minority of those patients will be found to have chemotherapy-sensitive disease and be able to go on to autologous stem cell transplantation,” Dr. Bishop said. “And even in that subgroup of patients, the outcomes are relatively poor.”
Accordingly, the phase 3 BELINDA study enrolled patients with aggressive non-Hodgkin lymphomas that either did not respond to first-line treatment or that reoccurred within 12 months.
The primary endpoint of the study was EFS, defined as the time from randomization to either stable or progressive disease at or after a week 12 assessment or to any-cause death at any time.
While that primary endpoint was not met for tisa-cel versus standard of care therapy, two other randomized, phase 3 studies presented at the ASH meeting did demonstrate that CAR T-cell therapy extended EFS when given as a second-line lymphoma treatment.
In the randomized, phase 3 ZUMA-7 trial, axicabtagene ciloleucel (axi-cel) significantly improved EFS versus standard of care in the treatment of patients with large B-cell lymphoma refractory to or relapsed within 12 months of adequate first-line therapy, according to investigators.
Similarly, the investigators said that treatment with lisocabtagene maraleucel (liso-cel) led to a significant improvement in EFS in TRANSFORM, a randomized, phase 3 clinical trial that enrolled patients with large B-cell lymphoma that was refractory to first-line therapy or else relapsed within 12 months of that treatment.
“It’s very possible that either or both the patient characteristics and the study design is what led to the difference in the top-line study results,” lymphoma specialist Andrew M. Evens, DO, said in an interview.
There were substantial differences between the studies in terms of what was allowed as optional bridging therapy and salvage therapy, according to Dr. Evens, associate director for clinical services and director of the lymphoma program at Rutgers Cancer Institute in New Brunswick, N.J.
“In ZUMA-7, they only allowed steroids as bridging therapy,” said Dr. Evens, who was not an investigator on any of the three second-line CAR T-cell studies.
In the BELINDA study, optional platinum-based chemotherapy bridging treatment allowed in one arm of the study could have potentially delayed tisa-cel infusion until after the week 6 assessment, study investigators reported in their ASH meeting abstract.
Differences in lymphodepleting therapy prior to CAR T-cell therapy could have also played a role. According to Dr. Bishop, the total doses of cyclophosphamide and fludarabine in BELINDA were 900 mg/m2 and 75 mg/m2, respectively, while in the other two trials, doses were 1,500 mg/m2 and 90 mg/m2, respectively.
Lymphodepleting chemotherapy is “extremely important” in the success of CAR T-cell therapeutic approaches, he noted at the press conference.
Dr. Bishop reported receiving consultancy fees from Arcellx, Autolus Therapeutics, Bristol-Myers Squibb, CRISPR, Kite/Gilead, and Novartis. He also reported research funding from Bristol-Myers Squibb and Kite/Gilead.
according to results of a randomized, phase 3 trial.
The chimeric antigen receptor (CAR) T-cell therapy did not improve event-free survival (EFS) in this phase 3 BELINDA study, potentially because of study design decisions or imbalances in relevant patient characteristics, according to the study investigators.
Despite the negative result, insights from this study will inform the development of future clinical trials of CAR T-cell therapy, said BELINDA investigator Michael R. Bishop, MD, of the David and Etta Jonas Center for Cellular Therapy, University of Chicago.
Findings of BELINDA, presented at the annual meeting of the American Society of Hematology, stand in contrast to two other high-profile CAR T-cell therapy studies also presented at the meeting. Those other studies demonstrated significant improvements in EFS in the second-line treatment of large B-cell lymphomas.
“All of us are excited to see that the other two trials were positive, and we were hoping that ours would be as well, but there are significant differences in the trial design,” Dr. Bishop said in a press conference held at the ASH meeting.
Tisagenlecleucel (tisa-cel), an anti-CD19 CAR T-cell therapy, is already approved by the Food and Drug Administration for the treatment of patients with relapsed or refractory large B-cell lymphomas after at least two other lines of systemic therapy.
The aim of the pivotal phase 3, randomized, multicenter BELINDA study was to evaluate tisa-cel earlier in the course of treatment for patients with more aggressive disease, according to Dr. Bishop.
About two-thirds of non-Hodgkin lymphoma patients will be cured with first-line treatment. However, very poor outcomes are seen among patients with disease that does not respond to the initial treatment or that reoccurs shortly afterward, Dr. Bishop said.
The standard of care approach for those patients is second-line therapy, he noted, usually with combination chemoimmunotherapy, followed by autologous stem cell transplant if the disease responds to chemotherapy.
“Unfortunately, only a minority of those patients will be found to have chemotherapy-sensitive disease and be able to go on to autologous stem cell transplantation,” Dr. Bishop said. “And even in that subgroup of patients, the outcomes are relatively poor.”
Accordingly, the phase 3 BELINDA study enrolled patients with aggressive non-Hodgkin lymphomas that either did not respond to first-line treatment or that reoccurred within 12 months.
The primary endpoint of the study was EFS, defined as the time from randomization to either stable or progressive disease at or after a week 12 assessment or to any-cause death at any time.
While that primary endpoint was not met for tisa-cel versus standard of care therapy, two other randomized, phase 3 studies presented at the ASH meeting did demonstrate that CAR T-cell therapy extended EFS when given as a second-line lymphoma treatment.
In the randomized, phase 3 ZUMA-7 trial, axicabtagene ciloleucel (axi-cel) significantly improved EFS versus standard of care in the treatment of patients with large B-cell lymphoma refractory to or relapsed within 12 months of adequate first-line therapy, according to investigators.
Similarly, the investigators said that treatment with lisocabtagene maraleucel (liso-cel) led to a significant improvement in EFS in TRANSFORM, a randomized, phase 3 clinical trial that enrolled patients with large B-cell lymphoma that was refractory to first-line therapy or else relapsed within 12 months of that treatment.
“It’s very possible that either or both the patient characteristics and the study design is what led to the difference in the top-line study results,” lymphoma specialist Andrew M. Evens, DO, said in an interview.
There were substantial differences between the studies in terms of what was allowed as optional bridging therapy and salvage therapy, according to Dr. Evens, associate director for clinical services and director of the lymphoma program at Rutgers Cancer Institute in New Brunswick, N.J.
“In ZUMA-7, they only allowed steroids as bridging therapy,” said Dr. Evens, who was not an investigator on any of the three second-line CAR T-cell studies.
In the BELINDA study, optional platinum-based chemotherapy bridging treatment allowed in one arm of the study could have potentially delayed tisa-cel infusion until after the week 6 assessment, study investigators reported in their ASH meeting abstract.
Differences in lymphodepleting therapy prior to CAR T-cell therapy could have also played a role. According to Dr. Bishop, the total doses of cyclophosphamide and fludarabine in BELINDA were 900 mg/m2 and 75 mg/m2, respectively, while in the other two trials, doses were 1,500 mg/m2 and 90 mg/m2, respectively.
Lymphodepleting chemotherapy is “extremely important” in the success of CAR T-cell therapeutic approaches, he noted at the press conference.
Dr. Bishop reported receiving consultancy fees from Arcellx, Autolus Therapeutics, Bristol-Myers Squibb, CRISPR, Kite/Gilead, and Novartis. He also reported research funding from Bristol-Myers Squibb and Kite/Gilead.
FROM ASH 2021
For leukemias, COVID-19 death risks tied to poor prognoses, ICU deferrals
, 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.
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).
, 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.
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).
, 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.
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).
FROM ASH 2021
Beta-thalassemia gene therapy achieves lasting transfusion independence
, 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.
, 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.
, 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.
FROM ASH 2021
Response endures in cemiplimab-treated patients with cutaneous SCC
MILAN – In an updated analysis of a pivotal phase 2 study, Michael R. Migden, MD, said at the World Congress of Dermatology.
Median duration of response was not reached at the time of the analysis, with probability of no progression or death above 80% at the 20-month mark, according to Dr. Migden, of the department of dermatology at the University of Texas MD Anderson Cancer Center, Houston.
The safety profile of cemiplimab in this study was comparable with what has been reported for other anti–programmed death agents, he said in an oral presentation at the meeting.
While the median time to response was less than 2 months, about one-fifth of patients with locally advanced disease had “unconventional” late responses, occurring up to 10 months after starting treatment, Dr. Migden said. “If you’re just putting someone on some agent like this for a few months, and say, ‘well, I don’t see anything improving,’ it could be one of these patients in this 20% that deserve a little bit longer therapy.”
Cemiplimab (Libtayo) is the only Food and Drug Administration–approved treatment for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC) who are not suitable for curative surgery or radiation, Dr. Migden said in his presentation. That approval was based in part on previously reported results from the phase 2 study, known as EMPOWER-CSCC-1, which demonstrated that cemiplimab had substantial antitumor activity and durable responses.
In this update on EMPOWER-CSCC-1, Dr. Migden described results for 78 patients with locally advanced CSCC and 59 with metastatic CSCC who received weight-based intravenous cemiplimab for up to 96 weeks, with optional retreatment for those who had disease progression during the follow-up period. This was an older population, with a mean age of 72 years, and more than 80% were male. About one-third had prior systemic therapy, and the majority had prior cancer-related radiotherapy and surgery.
The objective response rate was 43.6% in the locally advanced group and 49.2% in the metastatic group; this numerical difference of less than 3 percentage points was not statistically significant, according to Dr. Migden.
More importantly, he said, the disease control rate (responses, stable disease, and noncomplete response/nonprogressive disease) was 79.5% in the locally advanced group and 71.2% in the metastatic group.
Time to response was “quite rapid” at a median of 1.9 months in both groups, though 7 of the 34 responders in the locally advanced group had unconventional late responses, taking 6-10 months to get to the point of response, Dr. Migden said.
The probability of being event free (such as no progression or death) has remained relatively flat, he added. In the metastatic cohort, event-free probability was 96.4% at 6 months, 88.9% at 12 months, and 82.5% at 20 months, with a 16.5-month median duration of follow-up, while in the locally advanced cohort, the event-free probability was 96.2% at 6 months, 87.8% at both 12 months and 20 months, with a median follow-up of 9.3 months.
Serious treatment-emergent adverse events were reported for 28.5% in these patients, though Dr. Migden noted that treatment emergent does not necessarily mean related to the study drug. Immune-related adverse events of grade 3 or greater were seen in 11.7% of patients, and adverse events leading to discontinuation were reported for 8.8%.
Dr. Migden reported disclosures related to Regeneron, Novartis, Genentech, Eli Lilly, and Sun Pharmaceutical.
MILAN – In an updated analysis of a pivotal phase 2 study, Michael R. Migden, MD, said at the World Congress of Dermatology.
Median duration of response was not reached at the time of the analysis, with probability of no progression or death above 80% at the 20-month mark, according to Dr. Migden, of the department of dermatology at the University of Texas MD Anderson Cancer Center, Houston.
The safety profile of cemiplimab in this study was comparable with what has been reported for other anti–programmed death agents, he said in an oral presentation at the meeting.
While the median time to response was less than 2 months, about one-fifth of patients with locally advanced disease had “unconventional” late responses, occurring up to 10 months after starting treatment, Dr. Migden said. “If you’re just putting someone on some agent like this for a few months, and say, ‘well, I don’t see anything improving,’ it could be one of these patients in this 20% that deserve a little bit longer therapy.”
Cemiplimab (Libtayo) is the only Food and Drug Administration–approved treatment for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC) who are not suitable for curative surgery or radiation, Dr. Migden said in his presentation. That approval was based in part on previously reported results from the phase 2 study, known as EMPOWER-CSCC-1, which demonstrated that cemiplimab had substantial antitumor activity and durable responses.
In this update on EMPOWER-CSCC-1, Dr. Migden described results for 78 patients with locally advanced CSCC and 59 with metastatic CSCC who received weight-based intravenous cemiplimab for up to 96 weeks, with optional retreatment for those who had disease progression during the follow-up period. This was an older population, with a mean age of 72 years, and more than 80% were male. About one-third had prior systemic therapy, and the majority had prior cancer-related radiotherapy and surgery.
The objective response rate was 43.6% in the locally advanced group and 49.2% in the metastatic group; this numerical difference of less than 3 percentage points was not statistically significant, according to Dr. Migden.
More importantly, he said, the disease control rate (responses, stable disease, and noncomplete response/nonprogressive disease) was 79.5% in the locally advanced group and 71.2% in the metastatic group.
Time to response was “quite rapid” at a median of 1.9 months in both groups, though 7 of the 34 responders in the locally advanced group had unconventional late responses, taking 6-10 months to get to the point of response, Dr. Migden said.
The probability of being event free (such as no progression or death) has remained relatively flat, he added. In the metastatic cohort, event-free probability was 96.4% at 6 months, 88.9% at 12 months, and 82.5% at 20 months, with a 16.5-month median duration of follow-up, while in the locally advanced cohort, the event-free probability was 96.2% at 6 months, 87.8% at both 12 months and 20 months, with a median follow-up of 9.3 months.
Serious treatment-emergent adverse events were reported for 28.5% in these patients, though Dr. Migden noted that treatment emergent does not necessarily mean related to the study drug. Immune-related adverse events of grade 3 or greater were seen in 11.7% of patients, and adverse events leading to discontinuation were reported for 8.8%.
Dr. Migden reported disclosures related to Regeneron, Novartis, Genentech, Eli Lilly, and Sun Pharmaceutical.
MILAN – In an updated analysis of a pivotal phase 2 study, Michael R. Migden, MD, said at the World Congress of Dermatology.
Median duration of response was not reached at the time of the analysis, with probability of no progression or death above 80% at the 20-month mark, according to Dr. Migden, of the department of dermatology at the University of Texas MD Anderson Cancer Center, Houston.
The safety profile of cemiplimab in this study was comparable with what has been reported for other anti–programmed death agents, he said in an oral presentation at the meeting.
While the median time to response was less than 2 months, about one-fifth of patients with locally advanced disease had “unconventional” late responses, occurring up to 10 months after starting treatment, Dr. Migden said. “If you’re just putting someone on some agent like this for a few months, and say, ‘well, I don’t see anything improving,’ it could be one of these patients in this 20% that deserve a little bit longer therapy.”
Cemiplimab (Libtayo) is the only Food and Drug Administration–approved treatment for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC) who are not suitable for curative surgery or radiation, Dr. Migden said in his presentation. That approval was based in part on previously reported results from the phase 2 study, known as EMPOWER-CSCC-1, which demonstrated that cemiplimab had substantial antitumor activity and durable responses.
In this update on EMPOWER-CSCC-1, Dr. Migden described results for 78 patients with locally advanced CSCC and 59 with metastatic CSCC who received weight-based intravenous cemiplimab for up to 96 weeks, with optional retreatment for those who had disease progression during the follow-up period. This was an older population, with a mean age of 72 years, and more than 80% were male. About one-third had prior systemic therapy, and the majority had prior cancer-related radiotherapy and surgery.
The objective response rate was 43.6% in the locally advanced group and 49.2% in the metastatic group; this numerical difference of less than 3 percentage points was not statistically significant, according to Dr. Migden.
More importantly, he said, the disease control rate (responses, stable disease, and noncomplete response/nonprogressive disease) was 79.5% in the locally advanced group and 71.2% in the metastatic group.
Time to response was “quite rapid” at a median of 1.9 months in both groups, though 7 of the 34 responders in the locally advanced group had unconventional late responses, taking 6-10 months to get to the point of response, Dr. Migden said.
The probability of being event free (such as no progression or death) has remained relatively flat, he added. In the metastatic cohort, event-free probability was 96.4% at 6 months, 88.9% at 12 months, and 82.5% at 20 months, with a 16.5-month median duration of follow-up, while in the locally advanced cohort, the event-free probability was 96.2% at 6 months, 87.8% at both 12 months and 20 months, with a median follow-up of 9.3 months.
Serious treatment-emergent adverse events were reported for 28.5% in these patients, though Dr. Migden noted that treatment emergent does not necessarily mean related to the study drug. Immune-related adverse events of grade 3 or greater were seen in 11.7% of patients, and adverse events leading to discontinuation were reported for 8.8%.
Dr. Migden reported disclosures related to Regeneron, Novartis, Genentech, Eli Lilly, and Sun Pharmaceutical.
REPORTING FROM WCD2019
E-cigarettes beat nicotine patch for smoking cessation
E-cigarettes might be more effective for smoking cessation than nicotine replacement therapy, results of a randomized study of almost 900 adults suggest.
Rates of abstinence at 1 year were 18% for adults who used refillable e-cigarettes to wean themselves off smoking, according to the reported results, compared with about 10% for those who tried nicotine replacement therapies.
“This is particularly noteworthy given that nicotine replacement was used under expert guidance, with access to the full range of nicotine replacement products, and with 88.1% of participants using combination treatments,” said investigator Peter Hajek, PhD, of Queen Mary University of London, and his coauthors in the New England Journal of Medicine.
The findings contrast with those of earlier studies, which showed a lesser effect of e-cigarettes as a stop-smoking strategy, Dr. Hajek and coauthors wrote.
In previous studies, participants used first-generation cartridge-based e-cigarettes, while in the present study, they were given second-generation refillable e-cigarettes and free choice of e-liquids, the authors noted. Moreover, those previous studies provided limited face-to-face support, they said, but
The randomized study by Dr. Hajek and his colleagues included 886 adults in the United Kingdom attending stop-smoking services provided by the U.K. National Health Service. They were randomized to receive either an e-cigarette starter pack and one bottle of nicotine-containing e-liquid, or 3 months’ worth of nicotine replacement products of their own choosing. At the 52-week validation visits, the study participants received about the equivalence of about $26 U.S. dollars for their travel and time.
Abstinence from smoking at 52 weeks, which was verified by measuring expired carbon monoxide levels, was achieved in 18.0% of the e-cigarette group and 9.9% of the nicotine replacement group (relative risk, 1.83; 95% confidence interval, 1.30-2.58; P less than .001), according to the report.
However, the rate of continued e-cigarette use was “fairly high,” investigators wrote. Eighty percent of the e-cigarette group was still using their assigned product at 52 weeks, compared with just 9% in the nicotine replacement group.
“This can be seen as problematic if e-cigarette use for a year signals long-term use, which may pose as-yet-unknown health risks,” they said.
Tobacco withdrawal symptoms were less severe and satisfaction ratings were higher with e-cigarettes versus nicotine replacement therapy, similar to what had been observed in previous studies, investigators said.
They cited several limitations. For example, product assignments were not blinded. However, the investigators said they tried to “limit expectation effects by recruiting only participants with no strong product preference.”
Dr. Hajek reported grants and fees from Pfizer unrelated to the present study. Coauthors reported disclosures related to Pfizer and Johnson and Johnson, along with grants from the U.K. National Institute for Health Research.
SOURCE: Hajek P et al. N Engl J Med. 2019;380:629-37. doi: 10.1056/NEJMoa1808779.
Any smoking cessation benefit of e-cigarettes needs to be balanced against short- and long-term safety risks of using these products, according to authors of an editorial.
In the study by Hajek et al., the 1-year abstinence rate of 18% in the e-cigarette group compares favorably to what has been reported for Food and Drug Administration–approved smoking cessation treatments, according to Belinda Borelli, PhD, and George T. O’Connor, MD.
The short-term safety data in the trial are “reassuring,” with a low incidence of oropharyngeal irritation, no excess wheezing or dyspnea, and greater declines in cough and phlegm production versus the nicotine replacement group, Dr. Borelli and Dr. O’Connor said.
However, a notable finding was that 80% of participants in the e-cigarette group were still using the product at 1 year, versus just 9% in the nicotine replacement group. “This differential pattern of long-term use raises concerns about the health consequences of long-term e-cigarette use,” they said.
E-cigarette vapor generally has lower levels of toxins and fewer biologic effects than does tobacco smoke, but it has produced adverse biologic effects in animal models and human cells in vitro, according to the authors.
“These findings argue against complacency in accepting the transition from tobacco smoking to indefinite e-cigarette use as a completely successful smoking cessation outcome,” they wrote. Policy analysts need to be careful and do their due diligence to ensure all consequences of the policy options are fully understood, especially as pharmaceuticals account for greater costs in the Medicare program. Future policy analyses must account for changes to Medicare costs as well as beneficiary costs to understand the overall effects of policy changes.
Dr. Borelli is with the Center for Behavioral Science Research, department of health policy and health services research at the Henry M. Goldman School of Dental Medicine, Boston University. Dr. O’Connor is with the Pulmonary Center at Boston University and with the division of pulmonary, allergy, sleep, and critical care medicine at Boston Medical Center. Dr. Borelli had no disclosures; Dr. O’Connor reported disclosures with AstraZeneca and Janssen Pharmaceuticals. They made these comments in an accompanying editorial (N Eng J Med. 2019. doi: 10.1056/NEJMe1816406).
Any smoking cessation benefit of e-cigarettes needs to be balanced against short- and long-term safety risks of using these products, according to authors of an editorial.
In the study by Hajek et al., the 1-year abstinence rate of 18% in the e-cigarette group compares favorably to what has been reported for Food and Drug Administration–approved smoking cessation treatments, according to Belinda Borelli, PhD, and George T. O’Connor, MD.
The short-term safety data in the trial are “reassuring,” with a low incidence of oropharyngeal irritation, no excess wheezing or dyspnea, and greater declines in cough and phlegm production versus the nicotine replacement group, Dr. Borelli and Dr. O’Connor said.
However, a notable finding was that 80% of participants in the e-cigarette group were still using the product at 1 year, versus just 9% in the nicotine replacement group. “This differential pattern of long-term use raises concerns about the health consequences of long-term e-cigarette use,” they said.
E-cigarette vapor generally has lower levels of toxins and fewer biologic effects than does tobacco smoke, but it has produced adverse biologic effects in animal models and human cells in vitro, according to the authors.
“These findings argue against complacency in accepting the transition from tobacco smoking to indefinite e-cigarette use as a completely successful smoking cessation outcome,” they wrote. Policy analysts need to be careful and do their due diligence to ensure all consequences of the policy options are fully understood, especially as pharmaceuticals account for greater costs in the Medicare program. Future policy analyses must account for changes to Medicare costs as well as beneficiary costs to understand the overall effects of policy changes.
Dr. Borelli is with the Center for Behavioral Science Research, department of health policy and health services research at the Henry M. Goldman School of Dental Medicine, Boston University. Dr. O’Connor is with the Pulmonary Center at Boston University and with the division of pulmonary, allergy, sleep, and critical care medicine at Boston Medical Center. Dr. Borelli had no disclosures; Dr. O’Connor reported disclosures with AstraZeneca and Janssen Pharmaceuticals. They made these comments in an accompanying editorial (N Eng J Med. 2019. doi: 10.1056/NEJMe1816406).
Any smoking cessation benefit of e-cigarettes needs to be balanced against short- and long-term safety risks of using these products, according to authors of an editorial.
In the study by Hajek et al., the 1-year abstinence rate of 18% in the e-cigarette group compares favorably to what has been reported for Food and Drug Administration–approved smoking cessation treatments, according to Belinda Borelli, PhD, and George T. O’Connor, MD.
The short-term safety data in the trial are “reassuring,” with a low incidence of oropharyngeal irritation, no excess wheezing or dyspnea, and greater declines in cough and phlegm production versus the nicotine replacement group, Dr. Borelli and Dr. O’Connor said.
However, a notable finding was that 80% of participants in the e-cigarette group were still using the product at 1 year, versus just 9% in the nicotine replacement group. “This differential pattern of long-term use raises concerns about the health consequences of long-term e-cigarette use,” they said.
E-cigarette vapor generally has lower levels of toxins and fewer biologic effects than does tobacco smoke, but it has produced adverse biologic effects in animal models and human cells in vitro, according to the authors.
“These findings argue against complacency in accepting the transition from tobacco smoking to indefinite e-cigarette use as a completely successful smoking cessation outcome,” they wrote. Policy analysts need to be careful and do their due diligence to ensure all consequences of the policy options are fully understood, especially as pharmaceuticals account for greater costs in the Medicare program. Future policy analyses must account for changes to Medicare costs as well as beneficiary costs to understand the overall effects of policy changes.
Dr. Borelli is with the Center for Behavioral Science Research, department of health policy and health services research at the Henry M. Goldman School of Dental Medicine, Boston University. Dr. O’Connor is with the Pulmonary Center at Boston University and with the division of pulmonary, allergy, sleep, and critical care medicine at Boston Medical Center. Dr. Borelli had no disclosures; Dr. O’Connor reported disclosures with AstraZeneca and Janssen Pharmaceuticals. They made these comments in an accompanying editorial (N Eng J Med. 2019. doi: 10.1056/NEJMe1816406).
E-cigarettes might be more effective for smoking cessation than nicotine replacement therapy, results of a randomized study of almost 900 adults suggest.
Rates of abstinence at 1 year were 18% for adults who used refillable e-cigarettes to wean themselves off smoking, according to the reported results, compared with about 10% for those who tried nicotine replacement therapies.
“This is particularly noteworthy given that nicotine replacement was used under expert guidance, with access to the full range of nicotine replacement products, and with 88.1% of participants using combination treatments,” said investigator Peter Hajek, PhD, of Queen Mary University of London, and his coauthors in the New England Journal of Medicine.
The findings contrast with those of earlier studies, which showed a lesser effect of e-cigarettes as a stop-smoking strategy, Dr. Hajek and coauthors wrote.
In previous studies, participants used first-generation cartridge-based e-cigarettes, while in the present study, they were given second-generation refillable e-cigarettes and free choice of e-liquids, the authors noted. Moreover, those previous studies provided limited face-to-face support, they said, but
The randomized study by Dr. Hajek and his colleagues included 886 adults in the United Kingdom attending stop-smoking services provided by the U.K. National Health Service. They were randomized to receive either an e-cigarette starter pack and one bottle of nicotine-containing e-liquid, or 3 months’ worth of nicotine replacement products of their own choosing. At the 52-week validation visits, the study participants received about the equivalence of about $26 U.S. dollars for their travel and time.
Abstinence from smoking at 52 weeks, which was verified by measuring expired carbon monoxide levels, was achieved in 18.0% of the e-cigarette group and 9.9% of the nicotine replacement group (relative risk, 1.83; 95% confidence interval, 1.30-2.58; P less than .001), according to the report.
However, the rate of continued e-cigarette use was “fairly high,” investigators wrote. Eighty percent of the e-cigarette group was still using their assigned product at 52 weeks, compared with just 9% in the nicotine replacement group.
“This can be seen as problematic if e-cigarette use for a year signals long-term use, which may pose as-yet-unknown health risks,” they said.
Tobacco withdrawal symptoms were less severe and satisfaction ratings were higher with e-cigarettes versus nicotine replacement therapy, similar to what had been observed in previous studies, investigators said.
They cited several limitations. For example, product assignments were not blinded. However, the investigators said they tried to “limit expectation effects by recruiting only participants with no strong product preference.”
Dr. Hajek reported grants and fees from Pfizer unrelated to the present study. Coauthors reported disclosures related to Pfizer and Johnson and Johnson, along with grants from the U.K. National Institute for Health Research.
SOURCE: Hajek P et al. N Engl J Med. 2019;380:629-37. doi: 10.1056/NEJMoa1808779.
E-cigarettes might be more effective for smoking cessation than nicotine replacement therapy, results of a randomized study of almost 900 adults suggest.
Rates of abstinence at 1 year were 18% for adults who used refillable e-cigarettes to wean themselves off smoking, according to the reported results, compared with about 10% for those who tried nicotine replacement therapies.
“This is particularly noteworthy given that nicotine replacement was used under expert guidance, with access to the full range of nicotine replacement products, and with 88.1% of participants using combination treatments,” said investigator Peter Hajek, PhD, of Queen Mary University of London, and his coauthors in the New England Journal of Medicine.
The findings contrast with those of earlier studies, which showed a lesser effect of e-cigarettes as a stop-smoking strategy, Dr. Hajek and coauthors wrote.
In previous studies, participants used first-generation cartridge-based e-cigarettes, while in the present study, they were given second-generation refillable e-cigarettes and free choice of e-liquids, the authors noted. Moreover, those previous studies provided limited face-to-face support, they said, but
The randomized study by Dr. Hajek and his colleagues included 886 adults in the United Kingdom attending stop-smoking services provided by the U.K. National Health Service. They were randomized to receive either an e-cigarette starter pack and one bottle of nicotine-containing e-liquid, or 3 months’ worth of nicotine replacement products of their own choosing. At the 52-week validation visits, the study participants received about the equivalence of about $26 U.S. dollars for their travel and time.
Abstinence from smoking at 52 weeks, which was verified by measuring expired carbon monoxide levels, was achieved in 18.0% of the e-cigarette group and 9.9% of the nicotine replacement group (relative risk, 1.83; 95% confidence interval, 1.30-2.58; P less than .001), according to the report.
However, the rate of continued e-cigarette use was “fairly high,” investigators wrote. Eighty percent of the e-cigarette group was still using their assigned product at 52 weeks, compared with just 9% in the nicotine replacement group.
“This can be seen as problematic if e-cigarette use for a year signals long-term use, which may pose as-yet-unknown health risks,” they said.
Tobacco withdrawal symptoms were less severe and satisfaction ratings were higher with e-cigarettes versus nicotine replacement therapy, similar to what had been observed in previous studies, investigators said.
They cited several limitations. For example, product assignments were not blinded. However, the investigators said they tried to “limit expectation effects by recruiting only participants with no strong product preference.”
Dr. Hajek reported grants and fees from Pfizer unrelated to the present study. Coauthors reported disclosures related to Pfizer and Johnson and Johnson, along with grants from the U.K. National Institute for Health Research.
SOURCE: Hajek P et al. N Engl J Med. 2019;380:629-37. doi: 10.1056/NEJMoa1808779.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: The rate of smokers who continued to use e-cigarettes after 1 year was “fairly high,” which might be problematic.
Major finding: Abstinence from smoking at 52 weeks was achieved in 18.0% of the e-cigarette group and 9.9% of the nicotine replacement group (relative risk, 1.83; 95% confidence interval, 1.30-2.58; P less than .001).
Study details: Randomized study of 886 adults in the United Kingdom attending stop-smoking services provided by the U.K. National Health Service.
Disclosures: Dr. Hajek reported grants and fees from Pfizer unrelated to the present study.The coauthors reported disclosures related to Pfizer, and Johnson and Johnson, along with grants from the U.K. National Institute for Health Research.
Source: Hajek P et al. N Engl J Med. 2019;380:629-37. doi: 10.1056/NEJMoa1808779.