Liso-cel significantly improves outcomes in second-line DLBCL
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Second-line lisocabtagene maraleucel more than quadrupled EFS compared with standard therapy for patients with relapsed or refractory large B-cell lymphoma, according to study results presented at ASH Annual Meeting and Exposition.
Lisocabtagene maraleucel (Breyanzi, Bristol Myers Squibb) — a CD19-directed chimeric antigen receptor T-cell therapy — also conferred significant benefits in PFS and complete response rate, results of the randomized phase TRANSFORM study showed.
“We were very hopeful when we opened this clinical trial, and the results speak for themselves,” Manali Kamdar, MD, associate professor of medicine/hematology at University of Colorado School of Medicine and clinical director of lymphoma services at CU Cancer Center, told Healio. “The results from this trial have the potential to cause a paradigm shift in the standard of care.”
It has been about 2 decades since this population of high-risk patients had such an effective new therapeutic developed, Kamdar said. Salvage chemotherapy has been the only choice for patients who had primary refractory disease or who relapsed within 1 year of first-line chemotherapy.
“Of these patients, normally only a third respond to therapy and about a quarter have long-term remissions,” Kamdar said. “Clearly, this is an area of unmet clinical need.”
The multicenter TRANSFORM trial evaluated lisocabtagene maraleucel — also known as liso-cel — as second-line therapy for adults with previously treated diffuse large B-cell lymphoma compared with standard treatment, which included salvage therapy followed by high-dose chemotherapy and allogeneic hematopoietic stem cell transplant.
The analysis included 184 patients. Researchers randomly assigned 92 patients (median age, 60 years; range, 20-74; 48% men) to liso-cel. The other 92 patients (median age, 58 years; range, 26-75; 66% men) received standard therapy. Nearly three-quarters of patients in each treatment group were refractory to first-line therapy.
Forty-three (46.7%) patients in the standard therapy group received salvage therapy followed by high-dose chemotherapy and allogeneic HSCT. Fifty-eight patients (65%) in the liso-cel group had bridging therapy prior to CAR-T infusion.
Median follow-up was 6.2 months (range, 0.9–20).
The study achieved its primary endpoint, as liso-cel significantly improved median EFS compared with standard therapy (10.1 months vs. 2.3 months; HR = 0.34; P < .0001). Liso-cel also significantly increased median PFS (14.8 months vs. 5.7 months; HR = 0.4; P = .0001).
Sixty-six percent of patients assigned liso-cel achieved complete response to therapy, compared with 39% of patients assigned standard treatment (P < .0001).
Median OS favored liso-cel at the time of data cutoff; however, data were not yet mature (HR = 0.5; 95% CI, 0.25–1).
Researchers reported no cases of grade 4 or grade 5 cytokine release syndrome or neurotoxicity, and no treatment-related deaths occurred. Nearly half (49%) of all patients experienced CRS, but most cases were grade 1 or grade 2. Only one patient developed grade 3 CRS.
Twelve percent of patients experienced neurotoxicity, most of which were low-grade events. Four patients (4%) had grade 3 neurotoxicity.
Most patients treated with liso-cel reported better quality of life after treatment, Kamdar said.
The low incidence of CRS and neurotoxicity allowed many patients to remain as outpatients after CAR-T infusion, she added.
“This trial not only showed that lisocabtagene maraleucel is more efficacious but is also absolutely manageable with respect to its safety profile,” Kamdar told Healio. “Given that this high-risk patient population doesn’t have favorable outcomes, it would be a positive development to have the liso-cel label expanded to second-line therapy.”
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Kamdar M, et al. Abstract 91. Presented at: ASH Annual Meeting and Exposition; Dec. 11-14, 2021.
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