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Multicenter Study
. 2025 Apr 15;15(1):65.
doi: 10.1038/s41408-025-01271-3.

Outcomes of patients with relapsed/refractory lymphoplasmacytic lymphoma/waldenström macroglobulinemia treated with venetoclax: a multicenter retrospective analysis

Y Sawalha  1 , S Sarosiek  2 , R L Welkie  3 , S Seif  4 , S Thapa  5 , S Zanwar  6 , K Cahill  7 , R Treitman  8 , H Shah  9 , S Arora  10 , G Pongas  11 , A Winter  9 , A Major  12 , P A Riedell  13 , M L Palomba  14 , P Kapoor  6 , A Grajales-Cruz  5 , K H Shain  5 , S K Thomas  4 , J J Castillo  2
Affiliations
Multicenter Study

Outcomes of patients with relapsed/refractory lymphoplasmacytic lymphoma/waldenström macroglobulinemia treated with venetoclax: a multicenter retrospective analysis

Y Sawalha et al. Blood Cancer J. .

Abstract

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.

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Conflict of interest statement

Competing interests: A.G.C. reports honoraria from Janssen, Sanofi, Cellectar, Amgen, Bristol Myers Squibb, and Pfizer. A.W. has consulted for BeiGene, BTG Pharmaceuticals, AstraZeneca, and ADC Therapeutics. G.P. is a shareholder of Crispr Therapeutics and equity holder of Mevox Ltd and reports consultancy with ADC Therapeutics. J.J.C. received research funding from Abbvie, AstraZeneca, Beigene, Cellectar, Loxo, and Pharmacyclics, and consulting fees from Abbvie, AstraZeneca, Beigene, Cellectar, Janssen, Loxo, Mustang Bio, Nurix, and Pharmacyclics. K.H.S. reports honoraria from Amgen, Bristol Myers Squibb, Janssen, Adaptive, Sanofi, Regeneron, and Takeda, and research funding to the institution from AbbVie and Karyopharm, outside the submitted work. PAR reports serving as a consultant and/or advisory board member for AbbVie, Novartis, BMS, ADC Therapeutics, Kite/Gilead, Pfizer, CVS Caremark, Genmab, BeiGene, Janssen, Pharmacyclics, and Genentech/Roche. Honoraria from Adaptive Biotechnologies. Research support from BMS, Kite Pharma, Novartis, CRISPR Therapeutics, Calibr, Xencor, Fate Therapeutics, AstraZeneca, Genentech/Roche, Cellectis, Cargo Therapeutics, and Tessa Therapeutics. P.K. is the principal investigator of trials for which Mayo Clinic has received research funding from Amgen, Regeneron, Bristol Myers Squibb, Loxo Pharmaceuticals, Ichnos, Karyopharm, Sanofi, AbbVie and GlaxoSmithKline. Prashant Kapoor has received honorarium from Keosys and served on the Advisory Boards of BeiGene, Mustang Bio, Janssen, Pharmacyclics, X4 Pharmaceuticals, Kite Pharma, Oncopeptides, Ascentage, Angitia Bio, GlaxoSmithKline, Sanofi and AbbVie. SS received research funds or honoraria from Beigene, Cellectar, and ADC Therapeutics. ST received research funding from Ascentage Pharma, BMS, Genentech, Cellectar Biosciences, and Abbvie and has consulted for Cellectar Biosciences. YS received research funding from BeiGene, Genmab, and AbbVie and has consulted for ADC, Genmab, and Genentech.

Figures

Fig. 1
Fig. 1. Categorical response rates to venetoclax.
A All patients and according to (B) number of prior treatments, C treatment on trial vs. not, and D prior treatment with BTKi vs. not. BTKi Bruton tyrosine kinase inhibitor, CR complete response, MR minor response, ORR overall response rate, PR partial response, VGPR very good partial response.
Fig. 2
Fig. 2. Survival outcomes with venetoclax.
A PFS and B OS in the overall patient population. PFS in patients treated with venetoclax on clinical trial vs. not (C), in patients treated with venetoclax 400 mg vs. 800 mg (D), in patients treated with 1-2 prior lines of treatment vs. ≥3 (E), in patients with prior treatment with BTKi vs. not (F), in patients with TP53 wild-type vs. mutant (G), and in patients with CXCR4 wild-type vs. mutant (H).
See this image and copyright information in PMC

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