Second-Line Tisagenlecleucel vs Standard Salvage Therapy for Aggressive B-cell Lymphoma

Second-line treatment with tisangenlecleucel, an anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy, was not superior to standard salvage therapy for patients with aggressive B-cell lymphoma, according to findings from the phase 3 BELINDA trial.

“Patient outcomes are poor for aggressive B-cell non-Hodgkin’s lymphomas not responding to or progressing within 12 months after first-line therapy,” wrote lead author Michael Bishop, MD, department of hematology and oncology, the University of Chicago Medical Center, and coauthors.

The BELINDA trial aimed to compare the efficacy and safety of tisagenlecleucel vs standard second-line treatment strategies in patients with aggressive lymphoma refractory to or progressing within 12 months after first-line therapy. Standard second-line treatment strategies include salvage chemoimmunotherapy followed by high-dose therapy and autologous hematopoietic stem cell transplant (autoHSCT).

The primary trial end point was event-free survival (EFS), defined as the time from randomization to stable or progressive disease at or after the week 12 assessment or death. Secondary end points included response and safety.

A total of 322 patients were randomized in a 1:1 ratio to receive tisagenlecleucel with optional bridging therapy or standard care. Crossover to receive tisagenlecleucel was allowed under certain circumstances at or after the week 12 assessment.

At baseline, the percentage of patients with high-grade lymphomas was 24.1% in the tisagenlecleucel group compared to 16.9% in the standard care group. More patients in the tisagenlecleucel group had an International Prognostic Index score of 2 or higher (65.4% vs 57.5% in the standard care group).

Overall, 95.7% of the patients in the tisagenlecleucel group received tisagenlecleucel and 32.5% of the patients in the standard-care group received autoHSCT. The median time from leukapheresis to tisagenlecleucel infusion was 52 days.

At week 6, 25.9% of patients in the tisagenlecleucel group had lymphoma progression vs 13.8% in the standard care group. The median EFS in both groups was 3 months; the hazard ratio for event or death in the tisagenlecleucel group was 1.07 (95% confidence interval, 0.82 to 1.40; P = .61).

In the tisagenlecleucel group, 46.3% of patient experienced a response vs 42.5% in the standard care group. Adverse events leading to death occurred in 10 patients and 13 patients in each group, respectively.

“Tisagenlecleucel was not superior to standard salvage therapy in this trial. Additional studies are needed to assess which patients may obtain the most benefit from each approach,” concluded Dr Bishop and coauthors.

Source:
Bishop M, Dickinson M, Purtill D, et al. Second-Line Tisagenlecleucel or Standard Care in Aggressive B-Cell Lymphoma. N Engl J Med. Published online December 14, 2021. doi:10.1056/NEJMoa2116596.