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.
Authors
- Angela A. Dispenzieri (ORCID: https://orcid.org/0000-0001-8780-9512)
- Rafaël Fonseca (ORCID: https://orcid.org/0000-0002-5938-3769)
- Abiola Bukunmi Bolarinwa (ORCID: https://orcid.org/0000-0001-5812-1954)
- P. Leif Bergsagel (ORCID: https://orcid.org/0000-0003-1523-7388)
- David Dingli (ORCID: https://orcid.org/0000-0001-7477-3004)
- Francis K. Buadi (ORCID: https://orcid.org/0000-0003-3214-0203)
- Morie A. Gertz (ORCID: https://orcid.org/0000-0002-3853-5196)
- Taimur Sher (ORCID: https://orcid.org/0000-0003-1133-3970)
- Nelson Leung (ORCID: https://orcid.org/0000-0002-5651-1411)
- Shaji Kunnathu Kumar (ORCID: https://orcid.org/0000-0001-5392-9284)
- Saurabh Chhabra (ORCID: https://orcid.org/0000-0001-9117-8696)
- Madhu Nagaraj (ORCID: https://orcid.org/0009-0002-4786-3025)
- Prashant Kapoor (ORCID: https://orcid.org/0000-0002-4342-364X)
- Linda Banovic Baughn (ORCID: https://orcid.org/0000-0001-5229-4897)
- Nadine H. Abdallah (ORCID: https://orcid.org/0000-0001-9195-1589)
- Amie Fonder (ORCID: https://orcid.org/0000-0001-9488-8212)
- Moritz Binder (ORCID: https://orcid.org/0000-0001-9014-9658)
- Yi L. Hwa (ORCID: https://orcid.org/0000-0002-8163-2979)
- Sikander Ailawadhi (ORCID: https://orcid.org/0000-0002-8377-8111)
- Ricardo Parrondo (ORCID: https://orcid.org/0000-0002-9314-9933)
- Rahma Warsame (ORCID: https://orcid.org/0000-0003-0240-0326)
- Joselle Cook (ORCID: https://orcid.org/0000-0001-5335-9533)
- S. Vincent Rajkumar (ORCID: https://orcid.org/0000-0002-5862-1833)
- Julia E. Wiedmeier (ORCID: https://orcid.org/0000-0001-9434-5269)
- Wilson I. Gonsalves (ORCID: https://orcid.org/0000-0001-6890-969X)
- Mustaqeem Siddiqui (ORCID: https://orcid.org/0000-0002-4640-7311)
- Taxiarchis Kourelis (ORCID: https://orcid.org/0000-0001-8573-9434)
- Saurabh Zanwar (ORCID: https://orcid.org/0000-0001-5074-8453)
- Eli Muchtar (ORCID: https://orcid.org/0000-0003-2210-2174)
- Yi Lin (ORCID: https://orcid.org/0000-0002-1556-6416)
- Vivek Roy (ORCID: https://orcid.org/0000-0002-5950-4620)
- Michelle Rogers
- Suzanne R. Hayman (ORCID: https://orcid.org/0000-0001-9422-2621)
- Udit Yadav
- Miriam Hobbs
Institutions
- Jacksonville College (US)
- Mayo Clinic in Arizona (US)
- Mayo Clinic Hospital (US)
- Mayo Clinic in Florida (US)
Publication Details
- Journal
- Blood Cancer Journal
- Published
- 2025-04-04
- DOI
- https://doi.org/10.1038/s41408-025-01264-2
- Citations
- 3
- Primary Topic
- Multiple Myeloma Research and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 5.31
Funders
- Amgen
- Bristol-Myers Squibb
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- Alexion Pharmaceuticals
- Alnylam Pharmaceuticals
- Celgene
- Regeneron Pharmaceuticals
- Prothena
- BeiGene
- Syndax Pharmaceuticals
- Omeros Corporation
- Apellis Pharmaceuticals
- Genentech
- Pharmacyclics