Advances in precision therapy with venetoclax in multiple myeloma with t(11;14) and high BCL2 expression: A systematic review.

Abstract

e20535 Background: In multiple myeloma (MM), translocation t(11;14) has shown higher expression of B Cell Lymphoma 2 protein (BCL2)- a target for Venetoclax (VEN). This review highlights the role of precision therapy with VEN in t(11;14) MM. Methods: A systematic search of PubMed, Cochrane, Web of Science and Clinicaltrials.gov was performed for use of VEN in MM from inception to 1/2/20. 5 out of 183 studies were finalized (N = 512). Results: Out of 500 relapsed refractory (R/R) MM patients, 97 had t(11;14) and 168 had high BCL2. VEN as monotherapy had encouraging responses in t(11;14) MM patients with high BCL2:BCL2L1 (Kumar 2017). VEN when combined with proteasome inhibitors (PIs) achieved promising results. VEN achieved superior results with carfilzomib and dexamethasone (d) (ORR 100%) in t(11;14) MM patients (Costa 2018) as compared to bortezomib (B) and d (ORR 94%) (Moreau 2017). With high BCL2, VEN-Bd achieved ORR of 84% (CR 35%, VGPR 73%) versus placebo (ORR 83%; VGPR 33%) (Bellini 2019). Conclusions: Venetoclax achieved superior responses in RRMM pts with t(11;14) and high BCL2 expression. Further studies are warranted. [Table: see text]

Multiple Myeloma With Amplification of Chr1q: Therapeutic Opportunity and Challenges

“…Since their underlying biology is different, it is reasonable to assume that each subtype may have its own therapeutic vulnerabilities and that tailored therapy or precision medicine may improve patient outcomes (20,21). In practice, though, today the only subtype with an actionable, class-wide vulnerability is MM with translocation t (11;14), which is sensitive to BCL2 inhibition (20,22,23). Arguably, MM with t (11;14) is also the subtype with the most distinctive biological characteristics, including lymphoplasmacytic morphology, frequent expression of B-cell surface antigens, and a possible origin in bone marrow pro-B cells, as opposed to most other myelomas, which arise from post-germinal center B cells (24)(25)(26).…”