Venetoclax-based treatment combinations in relapsed/refractory multiple myeloma: practice patterns and impact of secondary cytogenetic abnormalities on outcomes.

Venetoclax (Ven), a BCL-2 inhibitor, has demonstrated efficacy in patients with relapsed/refractory multiple myeloma (RRMM) harboring a t(11;14) and/or elevated BCL-2 expression. However, data from clinical trial remain inconclusive. This retrospective study evaluated the efficacy and safety of Ven-based therapies in 232 MM patients without concurrent AL amyloidosis treated at Mayo Clinic sites between Jan 2015 and Dec 2023. The median age was 62 years, with a median of 3 prior lines of therapy. Among the cohort, 82% had t(11;14), and elevated BCL-2 expression was identified in 17 of 18 non-t(11;14) patients tested. Ven combinations included Ven-Dex (VenD; 48.3%), Proteasome Inhibitor-Ven (30.2%), and Daratumumab-Ven (19%) with other combinations making up the rest. The overall response rate was 57%; 64% for t(11;14) patients and 26% for non-t(11;14) patients. Median progression-free survival (PFS) was 9.4 months overall; 11.8 months for t(11;14) patients and 2.9 months for those without (p < 0.001). Among t(11;14) patients, the presence of del(17p) or 1q gain/amplification significantly reduced PFS to 7.7 months. Venetoclax-based regimens remain an important option for t(11;14) patients, but efficacy is limited in patients without a t(11;14). The presence of secondary high-risk cytogenetics imparts an inferior PFS.