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Article: Ibrutinib Monotherapy Effective in CXCR4- and MYD88- Mutated Waldenstrom Macroglobulinemia

Source: Cancer Therapy Advisor

Ibrutinib monotherapy is a highly active and tolerable option for treatment-naïve patients with Waldenström macroglobulinemia (WM), but may be affected by CXCR4-mutation status, according to a study published in the Journal of Clinical Oncology.1

Previous studies have demonstrated that ibrutinib is effective in patients with previously treated WM, but the effect of MYD88 and CXCR4 mutations on therapy response among patients with treatment-naïve WM has not been investigated in depth.

For this phase 2 (ClinicalTrials.gov Identifier: NCT02604511) study, researchers enrolled 30 patients with symptomatic WM to receive ibrutinib 420 mg daily. Study participants underwent tumor genotyping to establish the existence or absence of MYD88 and CXCR4 mutations; all patients were found to have mutations in MYD88 and 14 (47%) of patients were CXCR4-mutation-positive.

Results showed that upon receiving ibrutinib therapy, patients experienced significant improvements in median serum IgM levels (1513 mg/dL from 4370 mg/dL), bone marrow involvement (a decline to 20% from 65%), and hemoglobin level (a rise to 13.9 g/dL from 10.3 g/dL) (P < .001 for all comparisons). The overall response rate (defined as minor or better than minor) was 100%, and the major response rate (partial or better than partial) was 83%.

Compared with patients who had CXCR4-mutated WM, patients with wild-type CXCR4 had improved major response (71% and 94%, respectively), very good partial response (7% and 31%, respectively), and a shorter time to major response (7.3 months and 1.8 months, respectively; P = .01). After a median follow-up of 14.6 months, 2 patients — both of whom had CXCR4 mutations — experienced disease progression.

The 18-month progression-free survival rate of those treated with ibrutinib was 92% (95% CI, 73-98), and the overall survival rate was 100%.

The most frequently occurring grade 2 to 3 adverse events observed in more than 5% of patients included arthralgia, bruising, neutropenia, upper respiratory infections, urinary tract infections, atrial fibrillation, and hypertension.

Reference

  1. Treon SP, Gustine J, Meid K, et al. Ibrutinib monotherapy in symptomatic, treatment-naive patients with Waldenstrom macroglobulinemia [published online July 25, 2018]. J Clin Oncol. doi: 10.1200/JCO.2018.78.6426 

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