Venetoclax in the Treatment of Multiple Myeloma: A Retrospective Analysis of 79 Patients

Venetoclax, the first-in-class BCL-2 inhibitor, has shown efficacy in multiple myeloma (MM), particularly in patients with the t(11;14) translocation. This single-center retrospective analysis included MM patients treated with venetoclax from November 2017 to March 2023. Data encompassed demographics, disease characteristics, treatment regimens, and outcomes using median progression-free-survival (mPFS). Eligibility required patients to be aged 21 and older and to have received at least one venetoclax cycle. Seventy-nine patients (median age 61, 58.2% female) were included, with 31.6% having t(11;14). Patients had received a median of 5 lines of therapy (LOT) before venetoclax. The mPFS was 3.4 months, with a significant difference between t(11;14) positive (7.8 months) and negative patients (2.4 months, p < 0.01). Patients achieving a very good partial response or better had a mPFS of 7.1 months. Common adverse events included fatigue (31.6%), diarrhea (26.5%), and respiratory infections (30.3%). Univariable and multivariable analyses identified sex, disease response, and t(11;14) presence as significant survival predictors. Our real-world study suggests that venetoclax demonstrates moderate efficacy in heavily pretreated patients with relapsed/refractory MM (RRMM), compared to previous studies where patients received 1–3 prior LOT, such as the BELLINI study (mPFS of 22.4 months). Notably, the efficacy was higher in patients with t(11;14). Despite the heavily pretreated nature of our cohort, venetoclax was well tolerated, with a manageable safety profile and low incidence of severe infections, largely due to effective prophylactic measures. Venetoclax should be carefully considered in heavily pretreated populations, and further multicenter research is essential to better define its role in RRMM.