Venetoclax Shows Promise Among Previously Treated Patients With Waldenström Macroglobulinemia

Among patients with previously treated Waldenström macroglobulinemia (WM), venetoclax appears to be both safe and effective regardless of CXCR4 status, according to research published in the Journal of Clinical Oncology.

WM, in which MYD88 and CXCR4 mutations are common, is defined by immunoglobin M secretion in major organs, including the bone marrow. While several therapies, including Bruton tyrosine kinase (BTK) inhibitors, are used in patients with WM, the disease is considered incurable.

BCL2, which is overexpressed in WM cells, regardless of CXCR4 mutation status, has previously been established as a promising target in this patient population. Venetoclax, an oral therapy that targets BCL2, has previously shown promise in phase 1 study of WM. For this prospective phase 2 study ( Identifier: NCT02677324), researchers aimed to further evaluate the safety and efficacy of venetoclax among previously treated patients with WM.

Overall, 32 patients were enrolled and treated with venetoclax. At baseline, the average age was 66 years (range, 39-80), 56% of patients were male sex, the median immunoglobulin M level was 3512 mg/dL, the median number of prior therapy lines was 2 (range, 1-10), and 53% of patients had a CXCR4 mutation.

The overall response rate was 84%, the major response rate was 81%, and the very good partial response rate was 19%. No complete responses were noted, however.

The median time to minor and major responses was 1.9 and 5.1 months, respectively. Patients who had previously received a BTK inhibitor took longer to have a response (4.5 months vs 1.4 months without prior BTK inhibitor; P <.001).

Refractory patients were, furthermore, less likely to have a major response than were patients with relapsed disease (50% vs 95%, respectively; P =.007).

After a median follow-up of 33 months, the median progression-free survival was 30 months. Neither progression-free survival nor response rates were affected by CXCR4 mutation status.

The most common grade 2 or worse adverse events were neutropenia (17%), anemia (8%), and lymphopenia (6%). At the time of analysis, no deaths had been noted.

Disclosure: The study author(s) declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Castillo JJ, Allan JN, Siddiqi T, et al. Venetoclax in previously treated Waldenström macroglobulinemia. J Clin Oncol. Published online November 18, 2021. doi:10.1200/JCO.21.01194