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

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

Abstract 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 safet...

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Main Authors: Abiola Bolarinwa, Madhu Nagaraj, Saurabh Zanwar, Nadine Abdallah, P. Leif Bergsagel, Moritz Binder, Francis Buadi, Saurabh Chhabra, Joselle Cook, David Dingli, Angela Dispenzieri, Morie A. Gertz, Wilson Gonsalves, Suzanne Hayman, Prashant Kapoor, Taxiarchis Kourelis, Nelson Leung, Yi Lin, Eli Muchtar, Ricardo Parrondo, Vivek Roy, Taimur Sher, Mustaqeem Siddiqui, Rahma Warsame, Amie Fonder, Miriam Hobbs, Yi Lisa Hwa, Michelle Rogers, Udit Yadav, J. Erin Wiedmeier-Nutor, Linda B. Baughn, S. Vincent Rajkumar, Rafael Fonseca, Sikander Ailawadhi, Shaji Kumar
Format: Article
Language:English
Published: Nature Publishing Group 2025-04-01
Series:Blood Cancer Journal
Online Access:https://doi.org/10.1038/s41408-025-01264-2
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Summary:Abstract 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.
ISSN:2044-5385

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