Response to Ibrutinib in Symptomatic Untreated Waldenström’s Macroglobulinemia
In a study reported in the Journal of Clinical Oncology, Treon et al found that ibrutinib monotherapy was highly active in patients with previously untreated Waldenström’s macroglobulinemia, with better response in patients without CXCR4 mutation. Ibrutinib has been shown to be active in patients with previously treated disease, with MYD88 mutation being associated with major response and CXCR4 mutation delaying the time to response.
Study Details
The study included 30 symptomatic patients enrolled between January 2016 and December 2016. The last patient evaluation and survival updates were performed in January 2018. Patients received ibrutinib at 420 mg daily until disease progression or unacceptable toxicity. All patients had tumors with MYD88 mutation, and 14 patients (47%) had CXCR4 mutation.
Responses
Among all patients, median serum immunoglobulin M levels declined from 4,370 to 1,513 mg/dL, bone marrow involvement declined from 65% to 20%, and hemoglobin levels increased from 10.3 to 13.9 g/dL (P < .001 for all comparisons). Overall response (minor or better) and major response (partial or better) occurred in 100% and 83% of patients, respectively. The rates of major response (94% vs 71%) and very good partial response (31% vs 7%) were better and the time to major response shorter (1.8 vs 7.3 months, P = .01) in patients with wild-type vs mutant-CXCR4 disease. At a median follow-up of 14.6 months, 2 patients, both with CXCR4 mutation, had progressive disease. At the time of analysis, all patients were alive, with an estimated 18-month progression-free survival of 92%.
Adverse Events
The most common grade 2 or 3 treatment-related adverse events were hypertension (13%), atrial fibrillation (10%), arthralgia (7%), bruising (7%), neutropenia (7%), upper respiratory tract infection (7%), and urinary tract infection (7%). No grade 4 adverse events were observed.
The investigators concluded, “Ibrutinib is highly active, produces durable responses, and is safe as primary therapy in patients with symptomatic [Waldenström’s macroglobulinemia]. CXCR4 [mutation] status affects responses to ibrutinib.”
The study was supported by Pharmacyclics, Peter Bing, Leukemia and Lymphoma Society, Linda and Edward Nelson Fund for Waldenström Macroglobulinemia Research, and Bauman Fund for Waldenström Macroglobulinemia Research.
Steven P. Treon, MD, PhD, of the Bing Center for Waldenström’s Macroglobulinemia, Dana-Farber Cancer Institute, is the corresponding author of the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
