The “remarkable” efficacy of chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory mantle cell lymphoma as observed in recent trials supports its evaluation earlier in the course of treatment, according to Roch Houot, MD, PhD.
Patients with relapsed or refractory mantle cell lymphoma (MCL) who progress after treatment with a Bruton’s tyrosine kinase inhibitor (BTKi) have poor clinical outcomes, Dr. Houot, professor of hematology at Rennes (France) University Hospital, explained at the 3rd European CAR T-cell meeting.
Objective response rates in patients who relapse after BTKi therapy range from 25% to 42%, and median overall survival (OS) is less than 10 months with standard therapies, he said at the meeting, which is jointly sponsored by the European Society for Blood and Marrow Transplantation and the European Hematology Association.
The recent ZUMA-2 and TRANSCEND NHL 001 trials evaluating the CD19 CAR T-cell products brexucabtagene autoleucel (brexu-cel; Tecartus) and lisocabtagene maraleucel (liso-cel; Breyanzi), respectively, in patients with relapsed or refractory MCL after BTKi therapy, showed dramatically improved outcomes, compared with outcomes seen previously with standard salvage therapies.
The ORR in 68 patients treated with brexu-cel in ZUMA-2 was 92%, including complete response (CR) in 40 patients (67%) and partial response (PR) in 15 patients (25%) with the rare, aggressive subtype of B-cell lymphoma.
“Interestingly, among patients who achieved a CR, 70% remained in remission after a median follow-up of 17.5 months,” he said.
Median duration of response, progression-free survival, and overall survival were not reached at that time, and ongoing responses were consistent across prognostic subgroups, he added.
The ZUMA-2 findings led to accelerated approval of brexu-cel by the Food and Drug Administration in July 2020, as well as priority medicine designation by the European Medicines Agency in December 2020, for the treatment of MCL after two or more prior lines of systemic therapy including a BTKi.
The TRANSCEND study also included patients with MCL who were relapsed or refractory after two or more lines of therapy.
The ORR was 84% in 32 patients who completed treatment – including CRs in 66% and PRs in 19%. An additional 3% had stable disease and 9% of patients progressed, Dr. Houot said.
“The follow-up of the TRANSCEND study is still very short – the median is 5.9 months – so we don’t have survival data yet for these patients,” he noted.
Still, the efficacy in these studies is excellent, particularly considering the challenges of treating MCL patients who relapse or are refractory after BTKi treatment, he said, noting that most patients in both studies had poor prognostic factors.
Toxicities in both studies were similar to those seen in studies of patients with aggressive B-cell lymphomas who were treated with these drugs, he added.
“Longer follow-up is needed to better evaluate long-term efficacy,” he said, concluding that the results nonetheless “support evaluation of CAR T-cell therapy earlier in the therapeutic strategy of mantle cell lymphoma.”
Dr. Houot reported having no disclosures.