Advancing the understanding of venetoclax in t(11;14)-positive multiple myeloma: a comprehensive review of clinical evidence and future prospects

Abstract

Venetoclax is a selective inhibitor of the anti-apoptotic protein B-cell lymphoma 2 (BCL2), as a targeted therapy for multiple myeloma (MM) patients. It was initially approved by the United States Food and Drug Administration for the treatment of chronic lymphocytic leukemia in April 2016 and later for acute myeloid leukemia in October 2020. However, venetoclax is used as an off-label in a subset group of relapsed and refractory multiple myeloma (RRMM) patients with the presence of translocation t(11;14). Preclinical and clinical studies have highlighted the potential of venetoclax in the management of MM patients, with a specific focus on t(11;14) as a predictive biomarker for initiating venetoclax-based treatment. Later, several studies in RRMM patients that used venetoclax in combination with dexamethasone or/and proteasome inhibitors have shown promising results, in which management guidelines have included venetoclax as one of the options to treat MM patients. Hence, this review focuses on the use of venetoclax in RRMM, clinical efficacy, safety, dosing strategies, and predictive biomarkers for initiating venetoclax. Additionally, we discuss ongoing studies that are investigating different combination of venetoclax regimens in MM patients.

Keywords

• Venetoclax
• t(11;14)
• multiple myeloma
• AML, acute myeloid leukemia; BCL2, B-cell lymphoma 2; CAR T-cell, chimeric antigen receptor T-cell; CLL, chronic lymphocytic leukemia; FDA, Food and Drug Administration; IC50, half maximal inhibitory concentration; IL-6: interleukin 6; IMiD, immune-modulators; MM, multiple myeloma; ORR, overall response rate; PFS, progression-free survival; PI, proteasome inhibitor; RRMM, relapsed/refractory multiple myeloma