Director, Myeloma Clinical Program University of Wisconsin, Wisconsin, United States
Introduction: Bendamustine (B), singly or in combination, is reported to have significant activity in relapsed multiple myeloma, with several publications noting overall response rates (ORR) of 49%-60%, and PFS of 11.3 months when given in combination with bortezomib and lenalidomide (1, 2). The advent of CAR-T has also called into question the use of B, due to potential harmful effects on lymphocytes, that could ultimately influence the ability to collect adequate T cells for use, or possibly response to bispecific engagers.
Methods: We performed a retrospective analysis of all RRMM patients who received B or a B combination between 2015 to 2022.
Results: A total of 44 pts were treated. Median age 67 (range 41-83), Female (12/44 or 27%). Median previous lines of therapy 6 (range 3-15); 98% of pts were triple refractory (only 1 pt had not received anti CD 38 antibody therapy), and the majority (90%) had previous autologous transplant, and most were penta-refractory. Twenty-seven % of patients had high risk cytogenetics at diagnosis. Median time from diagnosis to B combination was 26 mo. (range 3-192 mo.). The median time on treatment was 3 mo. (range 1-12 mo.). ORR was 25% (11/44, with 1 VGPR, 10 PR) with a median PFS of 6.5 mo. and median OS of 18 mo. (range 3-48 mo.) calculated from time of B combo until death. One pt died of sepsis, grade 3/4 hematologic toxicity occurred in 50% of pts. Inclusion of bortezomib, pomalidomide or lenalidomide in the regimen did not appear to increase response rate. After failing B, the most effective salvage appeared to be second auto transplant or bispecific engager. Six patients subsequently received BCMA directed therapy, with 2/4 failing CAR-T treatment within 30 days of transplant.
Conclusions:
Conclusion: B either as a single agent or combination was associated with a 25% overall response rate. In heavily pretreated RRMM patients, alternative therapies should probably be considered, and B should likely be avoided in patients who are undergoing CAR-T transplantation.
Ref :1. Cerchione C, Catalano L, Nappi D, Rocco S, Palmieri S, Pareto AE, et al. Bendamustine-Bortezomib-Dexamethasone (BVD) in Heavily Pretreated Multiple Myeloma: Old/New in NOVEL Agents' Era. Blood. 2020;136(Supplement 1):2-3. 2. Kumar SK, Krishnan A, LaPlant B, Laumann K, Roy V, Zimmerman T, et al. Bendamustine, lenalidomide, and dexamethasone (BRD) is highly effective with durable responses in relapsed multiple myeloma. Am J Hematol. 2015;90(12):1106-10.
