Chimeric antigen receptor (CAR) T-cell therapy with lisocabtagene maraleucel could prove to be the new standard-of-care treatment for patients with relapsed or refractory large B-cell lymphoma in the second-line setting, according to data presented at the 2021 American Society of Hematology (ASH) Annual Meeting & Exposition.1
A planned interim analysis of the phase III TRANSFORM study comparing lisocabtagene maraleucel with salvage chemotherapy found that lisocabtagene maraleucel demonstrated highly statistically significant and clinically meaningful improvement in event-free survival, complete response rate, and progression-free survival as second-line therapy in patients with large B-cell lymphoma that was primary refractory or relapsed within 12 months after first-line therapy.
The study met its primary endpoint, showing an event-free survival of 10.1 months among patients receiving CAR T-cell therapy vs 2.3 months of event-free survival for those receiving the standard of care. Although overall survival data were immature at this data cutoff, study authors also reported a numerical trend favoring lisocabtagene maraleucel in overall survival.
Manali Kamdar, MD
“In this phase III randomized controlled trial, lisocabtagene maraleucel improved outcomes vs salvage chemotherapy followed by high-dose chemotherapy and transplantation and exhibited a favorable safety profile,” said Manali Kamdar, MD, Associate Professor of Hematology and Clinical Director of Lymphoma Services at the University of Colorado Cancer Center. “Despite a relatively short follow-up period of just over 6 months, the positive results of this study suggest that CAR T-cell therapy has the potential to become the new standard of care for patients who do not respond to initial chemotherapy or who relapse within 12 months.”
According to Dr. Kamdar, the current standard of care consisting of chemotherapy and transplantation remains ineffective at curing most patients with high-risk, relapsed large B-cell lymphoma, representing a huge unmet need in the field. “Only a quarter of transplant-intended patients with relapsed or refractory large B-cell lymphoma achieve durable remission,” she said. “The pivotal phase III TRANSFORM study was uniquely designed to challenge the current standard of care and address this unmet need.”
The U.S. Food and Drug Administration has approved lisocabtagene maraleucel as a third-line treatment of patients with lymphoma whose cancer fails to respond to two prior lines of therapy. The TRANSFORM study was designed to assess the efficacy of lisocabtagene maraleucel against the standard of care as a second-line treatment.
Improved Outcomes Reported
For this study, investigators randomly assigned 184 patients to receive lisocabtagene maraleucel or the standard of care. All participants had relapsed or refractory large B-cell lymphoma and were eligible to receive a stem cell transplant. As Dr. Kamdar reported, the study met its primary endpoint, showing an event-free survival hazard ratio of 0.349 (P < .0001), which represented a 65% reduction in the risk of events vs the standard of care.
In addition to improved event-free survival, the results of the interim analysis showed that lisocabtagene maraleucel significantly extended the median length of survival without disease progression by 9 months compared with the standard of care. -Lisocabtagene maraleucel also increased the likelihood of achieving a complete response to treatment, which occurred in 66% of those receiving the CAR T-cell product and 39% of those receiving the standard of care. Of 92 patients randomly assigned to receive the standard of care, said Dr. Kamdar, 50 patients ultimately crossed over to receive lisocabtagene maraleucel.
Investigators also reported an extremely favorable safety profile for the CAR T-cell therapy. Safety results of lisocabtagene maraleucel in the second-line setting were consistent with the profile in the third-line or later setting, said Dr. Kamdar, with extremely low rates of breakthrough cytokine-release syndrome and neurotoxicity. Although approximately half of patients receiving lisocabtagene maraleucel experienced cytokine-release syndrome and 12% experienced neurologic toxicity, they were mostly low grade. It is pertinent to note that no grade 4 or 5 cytokine-release syndrome or neurologic events were reported.
“This is a breakthrough therapy that has shown superiority over the standard of care in terms of efficacy,” Dr. Kamdar concluded. “We are excited about the potential of this study to change the existing standard of care in these high-risk patients.”
DISCLOSURE: Dr. Kamdar has served on the speakers bureau for SeaGen; has served as a consultant to AbbVie, AstraZeneca, Celgene, Bristol Myers Squibb, -Adaptive Biotechnologies, ADC Therapeutics, and Beigene; and has received research funding from TG Therapeutics, Genentech, and Novartis.
1. Kamdar M, Solomon SR, Arnason JE, et al: Lisocabtagene maraleucel, a CD19-directed chimeric antigen receptor T cell therapy, versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma: Results from the randomized phase 3 TRANSFORM study. 2021 ASH Annual Meeting & Exposition. Abstract 91. Presented December 11, 2021.
Laurie H. Sehn, MD, MPH
The moderator of the session, Laurie H. Sehn, MD, MPH, Clinical Professor at the BC Cancer Centre for Lymphoid Cancer and University of British Columbia, Vancouver, Canada, called the results of TRANSFORM trial “quite remarkable” and said chimeric antigen receptor...