Venetoclax for the Treatment of Multiple Myeloma: Outcomes Outside of Clinical Trials

ABSTRACT

INTRODUCTION: Multiple myeloma (MM) remains an incurable disease despite incorporation of novel agents. Venetoclax, a B-cell lymphoma 2 (BCL-2) inhibitor is approved for some hematologic malignancies but not yet for MM, although clinical trials have shown efficacy in patients with MM particularly those harboring t(11;14).

METHODS: We reviewed the medical records of relapsed and/or refractory MM patients to study the efficacy and safety of venetoclax used outside of clinical trials at Mayo Clinic between December 2016 and March 2019. The data cut-off date was August 06, 2020.

RESULTS: We identified 56 patients of whom 42 (75%) harbored t(11;14). The median number of prior therapies was 6 (range 1-15) and 14% of patients had received ≥10 prior lines of therapy. Fifty-three (95%) patients were refractory to an immunomodulatory drug and proteasome inhibitor. Venetoclax was used as monotherapy or doublet, in combination with dexamethasone in 55% (n=31) and a triplet or quadruplet in 45% of patients. No patient experienced tumor lysis syndrome. Overall response rate in 52 evaluable patients was 44%. The median time to best response was 2 months and median duration of response was 13.6 months. The median PFS for the entire cohort was 5.8 (95% CI 4.9-10.3) months and median OS was 28.4 (95% CI 14.6-not reached) months. The presence of t(11;14) was associated with improved PFS (median 9.7 months vs. 4.2 months, p=0.019) and OS (median not reached vs. 10.8 9 months, p=0.015) .

CONCLUSION: Venetoclax demonstrates encouraging activity in heavily-treated patients with relapsed/refractory MM, particularly t(11;14) patient-population. This article is protected by copyright. All rights reserved.