Ibrutinib May Be Effective as First-Line Agent in Treatment of Waldenström's Macroglobulinemia

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The effectiveness of ibrutinib in the frontline setting has not been definitively established.
The effectiveness of ibrutinib in the frontline setting has not been definitively established.

Ibrutinib monotherapy leads to robust activity and produces durable responses in the first-line setting for patients with Waldenström's macroglobulinemia (WM), according to a poster presentation given at the Presidential Symposium during the 23rd Annual Congress of the European Hematology Association in Stockholm, Sweden.1

Previous studies have demonstrated that ibrutinib — a Bruton's tyrosine kinase inhibitor — is highly effective among patients with previously treated WM and leads to significant improvements in survival outcomes. Its effectiveness in the frontline setting however, as well as the impact of the CXCR4 mutation — a highly prevalent activating mutation among patients with WM — on ibrutinib efficacy, has not been definitively established.

For this study, researchers assigned 30 untreated, symptomatic patients with WM to receive ibrutinib 420 mg once daily until progression or unacceptable toxicity. Genotype analyses showed that all patients were carriers of the MYD88 mutation and 47% (14) of patients also had the CXCR4 mutation.

The overall response rate and major response rate (defined as greater than a partial response) was 100% and 83% respectively, and the 18-month progression-free survival was 92% (95% CI, 73-98). All patients remained alive at the time of analysis.

Upon receiving ibrutinib therapy, median serum IgM levels were decreased to 1,513 mg/dL from 4370 mg/dL, bone marrow involvement was reduced from 65% to 20%, and hemoglobin increased to 13.9 g/dL from 10.3 g/dL (P < .0001).

Investigators reported that patients with CXCR4 mutations had significantly poorer outcomes with ibrutinib as frontline therapy compared with wild-type. Major response was 94% versus 71% among wild-type patients and those with the mutation, respectively, and very good partial response rates were 31% and 7%, respectively. Patients with the wild-type allele also had a median time to major response of 1.8 months compared with 7.3 months among patients with CXCR4 mutations (P = .01). After a median follow-up of 14.6 months, 2 patients—both of whom displayed CXCR4 mutations — experienced disease progression.

The most frequently observed grade 2 to 3 treatment-related adverse events included arthralgia, bruising, neutropenia, upper respiratory tract infections, urinary tract infections, atrial fibrillations, and hypertension. No grade 4 or other unexpected toxicities were reported.

Reference

  1. Treon S, Gustine J, Meid K, et al. Ibrutinib monotherapy in symptomatic, treatment-naive patients with Waldenstrom's macroglobulinemia. Poster presentation at: 2018 European Hematology Association 23rd Annual Congress; June 2018; Stockholm, Sweden.

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