Ibrutinib Dose Reduction Did Not Affect PFS in Waldenström Macroglobulinemia

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The need for dose reductions did not significantly affect progression-free survival in patients with WM treated with ibrutinib.
The need for dose reductions did not significantly affect progression-free survival in patients with WM treated with ibrutinib.
The following article features coverage from the American Society of Hematology (ASH) 2018 meeting. Click here to read more of Cancer Therapy Advisor's conference coverage.

Older patients with Waldenstrom macroglobulinemia (WM) and those who achieved major responses were more likely to need a dose reduction while on treatment with ibrutinib, according to study findings presented at the 60th American Society of Hematology (ASH) Annual Meeting in San Diego, California. However, these dose reductions did not seem to significantly affect progression-free survival (PFS).

Jorge J. Castillo, MD, of Dana Farber Cancer Institute, and colleagues report that ibrutinib dose reductions are sometimes needed in patients with WM to manage toxicity; however, data were lacking on whether these reductions affected progression-free survival.

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To test that, Castillo and colleagues evaluated 217 patients with WM being treated with ibrutinib. All patients were initiated on ibrutinib 420 mg once daily.

At a median follow-up of longer than 2 years, less than one-third of patients (27%) required a dose reduction. Of those who did need a dose reduction, 78% were reduced to 280 mg daily, 21% to 140 mg daily, and 2% to 140 mg every other day. On average, patients' doses were reduced from 420 mg to 280 mg in 155 days and from 280 mg to 140 mg in 55 days. Among the reasons listed for dose reductions were cytopenia (24%), arrhythmia (17%), musculoskeletal discomfort (15%), constitutional symptoms (11%), and skin changes/rash (4%).

Dose reductions were more likely to occur in patients older than 65 (76% vs 47%; P <.001), those with a higher International Prognostic Scoring System score for WM at treatment initiation (P =.03), and in those who had achieved major response (93% vs 69%; P <.001). No differences in rate of dose reduction were found for sex, hemoglobin levels, platelet counts, beta-2-microglobulin levels, serum IgM levels, bone marrow involvement, previous treatment, MYD88 and CXCR4 mutations, and time from diagnosis to ibrutinib initiation.

Overall, patients with mutated MYD88 and those who attained major response had better progression-free survival. However, those who had a dose reduction in ibrutinib experienced no significant difference in progression-free survival compared with those whose dose was not reduced.

Read more of Cancer Therapy Advisor's coverage of the ASH 2018 meeting by visiting the conference page.


  1. Castillo JJ, Gustine J, Keezer A, et al. Ibrutinib dose reduction does not affect progression-free survival in patients with Waldenstrom macroglobulinemia. Poster presentation at: American Society of Hematology 60th Annual Meeting & Exposition; December 1-4, 2018; San Diego, CA.

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