Safety and Efficacy of Venetoclax Salvage Therapy in Relapsed/Refractory Multiple Myeloma with and without t(11;14)

Abstract

Background: The BCL2 inhibitor Venetoclax (Ven) is an effective treatment option in multiple myeloma (MM). However, despite the recent inclusion in European MM treatment guidelines, no approval has yet been granted for the treatment of MM and the optimal dosage, combination partners and timing of treatment remain under investigation. Methods: We conducted an analysis of 40 MM patients treated with Ven at our institution from November 2017 until June 2022. 64% of them had a t(11;14), all were heavily pretreated with a median of 7 lines of prior lines of therapy, and 75% were penta-refractory. High-risk features were enriched in the cohort (47% for all 38 with FISH available via IMWG criteria). Risk was evenly distributed between patients with and without t(11;14). Patients received either Ven alone or in combination with other MM drugs over a median of 5 cycles. Results: The full cohort overall response rate reached 53%, ten patients (25%) achieved partial remission (PR), seven patients (17.5%) went into VGPR and four patients (10%) had a complete remission (CR). Moreover, stable disease (SD) for three months or longer was achieved in seven patients (18%). The median progression-free survival was 5.1 months and the duration of response reached 9.6 months. Subgroup analysis revealed that patients harboring t(11;14) had significantly increased PFS and OS: Median PFS reached 11.2 vs. 4.4 months and median OS was not reached vs. 12.8 months, respectively. Overall, hematological AEs grade 3 or higher were documented in 65% of patients and three high-grade infectious complications (7.5%) occurred. Two of these patients died from sepsis, another recovered from pneumonia with severe sequelae. Interestingly, in contradiction to the BELLINI experience, all high-grade infectious complications occurred in the t(11;14) positive cohort. Conclusion: In our real-world analysis, Ven demonstrated to be an effective MM treatment option for t(11;14) positive relapsed/refractory MM. However, the significant infectious complications suggest antibiotic prophylaxis and careful monitoring of patients undergoing Ven treatment.