Outcomes of patients with relapsed/refractory lymphoplasmacytic lymphoma/waldenström macroglobulinemia treated with venetoclax: a multicenter retrospective analysis
Venetoclax showed promising activity in a small phase II trial in relapsed/refractory Waldenström macroglobulinemia (WM). To report the clinical activity of venetoclax and prognostic factors associated with outcomes in a larger cohort, we retrospectively identified 76 patients with relapsed/refractory lymphoplasmacytic lymphoma (LPL)/WM treated with venetoclax monotherapy at nine US medical centers. The median age at venetoclax treatment initiation was 66 years. MYD88, CXCR4, and TP53 mutations were detected in 65 (94%), 23 (40%), and 10 (22%) patients, respectively. The median number of prior lines of treatment was 3, including covalent BTK inhibitor in 82% and alkylating agent in 71% of patients. The overall and major response rates to venetoclax were 70% and 63%, respectively. The median and 2-year progression-free survival (PFS) were 28.5 months and 57%, respectively. The median and 2-year overall survival were not reached and 82%, respectively. Prior treatment with BTK inhibitor was the only factor associated with PFS in multivariate analysis (hazard ratio 2.97, p = 0.012). Venetoclax dose interruptions and/or reductions occurred in 27 patients (41%). Five patients (7%) developed laboratory tumor lysis syndrome (TLS), including 3 (4%) with clinical TLS. Venetoclax resulted in a high response rate and a prolonged PFS in patients with heavily pretreated LPL/WM.
Authors
- Hiral Shah (ORCID: https://orcid.org/0000-0003-0204-451X)
- Peter A. Riedell (ORCID: https://orcid.org/0000-0003-2719-0580)
- Ken Shain
- Sheeba K. Thomas (ORCID: https://orcid.org/0000-0001-8596-7058)
- Allison Winter (ORCID: https://orcid.org/0000-0002-8437-7539)
- Yazeed Sawalha (ORCID: https://orcid.org/0000-0001-6355-3671)
- Jorge J. Castillo (ORCID: https://orcid.org/0000-0001-9490-7532)
- Sameh Seif (ORCID: https://orcid.org/0000-0002-2752-0730)
- Prashant Kapoor (ORCID: https://orcid.org/0000-0002-4342-364X)
- Kirk E. Cahill (ORCID: https://orcid.org/0000-0002-1313-4943)
- Georgios Pongas (ORCID: https://orcid.org/0000-0002-6594-8682)
- Maria Lia Palomba (ORCID: https://orcid.org/0000-0001-5099-9156)
- Shayna Sarosiek (ORCID: https://orcid.org/0000-0002-0075-6735)
- Ajay Major (ORCID: https://orcid.org/0000-0001-7261-1335)
- Rachel Treitman
- Saurabh Zanwar (ORCID: https://orcid.org/0000-0001-5074-8453)
- Sudip Thapa (ORCID: https://orcid.org/0000-0001-6139-0493)
- Ariel Felipe Grajales-Cruz (ORCID: https://orcid.org/0000-0003-0999-1771)
- Shagun Arora (ORCID: https://orcid.org/0000-0002-6184-1968)
- Rina Li Welkie (ORCID: https://orcid.org/0000-0001-9477-4581)
Institutions
- Loyola University Medical Center (US)
- Cleveland Clinic (US)
- Memorial Sloan Kettering Cancer Center (US)
- The University of Texas MD Anderson Cancer Center (US)
- University of Miami (US)
- University of California, San Francisco (US)
- The Ohio State University Wexner Medical Center (US)
- Moffitt Cancer Center (US)
- University of Illinois Chicago (US)
- University of Chicago (US)
- Dana-Farber Cancer Institute (US)
- Mayo Clinic in Arizona (US)
- University of Colorado Cancer Center (US)
- University of Colorado Denver (US)
Publication Details
- Journal
- Blood Cancer Journal
- Published
- 2025-04-15
- DOI
- https://doi.org/10.1038/s41408-025-01271-3
- Citations
- 4
- Primary Topic
- Chronic Lymphocytic Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 6.50