Bendamustine as Lymphodepletion for Brexucabtagene Autoleucel Therapy of Mantle Cell Lymphoma

• Published in: Transplantation and cellular therapy Vol. 30; no. 7; pp. 726.e1 - 726.e8
• Main Authors: Chong, Elise A., Chong, Emeline R., Therwhanger, Dylan, Nasta, Sunita D., Landsburg, Daniel J., Barta, Stefan K., Svoboda, Jakub, Gerson, James N., Ghilardi, Guido, Paruzzo, Luca, Fraietta, Joseph A., Weber, Elizabeth, Stefano, Natalie, Porter, David L., Frey, Noelle V., Garfall, Alfred L., Ruella, Marco, Schuster, Stephen J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2024
• Subjects: Adult; Aged; Antigens, CD19 - immunology; Antineoplastic Agents, Alkylating - administration & dosage; Antineoplastic Agents, Alkylating - therapeutic use; Bendamustine; Bendamustine Hydrochloride - administration & dosage; Bendamustine Hydrochloride - therapeutic use; Brexucabtagene autoleucel; CAR T cells; CAR-T; Female; Humans; Immunotherapy, Adoptive - methods; Lymphoma, Mantle-Cell - drug therapy; Male; Mantle cell lymphoma; MCL; Middle Aged; Retrospective Studies; Treatment Outcome; Vidarabine - administration & dosage; Vidarabine - analogs & derivatives; Vidarabine - therapeutic use; Brexucabtagene autoleucel; CAR T cells; Bendamustine; CAR-T; Mantle cell lymphoma; MCL
• ISSN: 2666-6367; 2666-6367
• DOI: 10.1016/j.jtct.2024.03.015

•Bendamustine lymphodepletion is a safe and effective alternative prior to brexu-cel.•CAR T cell expansion was observed on day 7 and persisted for at least 6 months. Brexucabtagene autoleucel (brexu-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for treatment of relapsed/refractory mantle cell lymphoma (MCL). During a fludarabine shortage, we used bendamustine as an alternative to standard cyclophosphamide/fludarabine (cy/flu) lymphodepletion (LD) prior to brexu-cel. We assessed MCL patient outcomes as well as CAR T-cell expansion and persistence after brexu-cel following bendamustine or cy/flu LD at our center. This was a retrospective single institution study that utilized prospectively banked blood and tissue samples. Clinical efficacy was assessed by 2014 Lugano guidelines. CAR T-cell expansion and persistence in peripheral blood were assessed on day 7 and at ≥month 6 for patients with available samples. Seventeen patients received bendamustine and 5 received cy/flu. For the bendamustine cohort, 14 (82%) received bridging therapy and 4 (24%) had CNS involvement. Fifteen patients (88%) developed CRS with 4 (24%) ≥grade 3 events. Six (35%) patients developed ICANS with 4 (24%) events ≥grade 3. No patient had ≥grade 3 cytopenias at day 90. Best objective (BOR) and complete response (CRR) rates were 82% and 65%, respectively. At 24.5 months median follow-up, 12-month progression-free survival (PFS) was 45%, 24-month PFS was 25%, and median duration of response was 19 months. Median OS was not reached. BOR was 25% (1/4) for patients with CNS involvement. CAR transgene expansion after bendamustine LD was observed on day 7 in all (4/4) patients tested and persisted at ≥6 months (2/2), regardless of response. Bendamustine LD before brexu-cel for MCL is feasible and safe with a lower frequency and shorter duration of cytopenias than reported for cy/flu. Both CAR T-cell expansion and persistence were observed after bendamustine LD. Outcomes appear comparable to the real world outcomes reported with cy/flu LD. [Display omitted]