FDA Approval Summary: Lisocabtagene Maraleucel for Second-Line Treatment of Large B-Cell Lymphoma.

Abstract

In June 2022, the FDA extended the indication for lisocabtagene maraleucel (liso-cel) to include adults with large B-cell lymphoma (LBCL) who have refractory disease or relapse within 12 months of first-line chemoimmunotherapy (CIT), as well as transplant-ineligible adults with refractory disease or relapse after first-line CIT. Two clinical trials evaluating a single infusion of liso-cel preceded by lymphodepleting chemotherapy supported the second-line indications. TRANSFORM is a randomized, phase 3, open-label trial comparing liso-cel with standard second-line therapy, including planned autologous hematopoietic stem cell transplantation (HSCT), in 184 transplant-eligible patients. On interim analysis, event-free survival (EFS) by independent review committee (IRC) assessment was statistically significantly improved for the liso-cel arm, with a stratified hazard ratio of 0.34 [95% confidence interval (CI), 0.22-0.51; P < 0.0001]; the estimated median EFS was 10.1 months in the liso-cel arm versus 2.3 months in the control arm. PILOT is a single-arm phase 2 trial of second-line liso-cel in patients who were transplant-ineligible due to age or comorbidities but had adequate organ function for chimeric antigen receptor (CAR) T-cell therapy. Among 61 patients who received liso-cel (median age, 74 years), the IRC-assessed complete response rate was 54% (95% CI, 41-67). Among patients achieving complete response, the estimated 1-year rate of continued response was 68% (95% CI, 45-83). Of the 268 patients combined who received liso-cel as second-line therapy for LBCL, cytokine release syndrome occurred in 45% (Grade 3, 1.3%) and CAR T-cell-associated neurologic toxicities occurred in 27% (Grade 3, 7%), warranting a continued risk evaluation and mitigation strategy.