New Data Support Bendamustine Lymphodepletion Before Brexu-Cel for MCL

A retrospective study has found lymphodepletion with bendamustine before brexucabtagene autoleucel (brexu-cel) chimeric antigen receptor (CAR) T-cell therapy to be an effective and safe approach in relapsed or refractory mantle cell lymphoma (MCL). Findings from the study were recently published in Transplantation and Cellular Therapy.

“Outcomes appear comparable to the real world outcomes reported with cyclophosphamide plus fludarabine lymphodepletion,” wrote lead author Elise A Chong, MD, of the Abramson Cancer Center at the University of Pennsylvania in Philadelphia.

The study examined prospectively banked blood and tissue samples from 22 patients who underwent brexu-cel for relapsed or refractory MCL, 17 of whom received lymphodepletion beforehand as bendamustine and 5 as cyclophosphamide plus fludarabine. Among the patients who received bendamustine, 24% had disease with central nervous system (CNS) involvement and 82% received bridging therapy.

The patients who received bendamustine lymphodepletion had a median follow-up of 24.5 months. They had a best objective response (BOR) rate of 82% and a complete response rate of 65%. The cohort did not reach median overall survival and had a 12-month progression-free survival (PFS) of 45% and a 24-month PFS of 25%. The median duration of response was 19 months and patients with CNS involvement achieved a BOR rate of 25%.

Four of the patients who received bendamustine had peripheral blood samples that could be evaluated for the presence of CAR-T expansion following brexu-cel. This expansion was evident in all these patients at day 7 following brexu-cel, and in two patients, the expansion persisted for at least six months independently of treatment response.

Regarding safety results in the bendamustine cohort, at day 90 of the study, none of the patients had experienced grade 3 or worse cytopenia. Cytokine release syndrome developed in 88% of the cohort and immune effector cell-associated neurotoxicity syndrome occurred in 35%.

“These data serve as a benchmark for patients with MCL who receive bendamustine as lymphodepletion prior to brexu-cel during periods of fludarabine shortage or with contraindications to cyclophosphamide or fludarabine,” Dr. Chong wrote.

Reference

Chong EA, Chong ER, Therwhanger D, et al. Bendamustine as lymphodepletion for brexucabtagene autoleucel therapy of mantle cell lymphoma. Transplant Cell Ther. 2024;30(7):726.e1-726.e8. doi:10.1016/j.jtct.2024.03.015