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No Statistically Significant Impact of CXCR4 Mutations on Efficacy of Ibrutinib in WM
Ibrutinib is a standard-of-care first line therapy for patients with Waldenstrom macroglobulinemia (WM). However, long-term follow-up results from a phase 2 trial found that for patients with WM treated with ibrutinib monotherapy, none experienced a complete response, and any impact of a CXCR4 mutations did not reach statistical significance.
“The genomic landscape of WM is composed of recurrent mutations in the MYD88 and CXCR4 genes, which can be detected in 90-95% and 30-40% of patients with WM, respectively,” explained Jorge Castillo, MD, Dana Farber Cancer Institute, Boston, and co-authors. “Our data show that ibrutinib monotherapy, as primary therapy for WM, induced a high rate of durable responses and further affirms ibrutinib as a standard of care in treatment-naive patients with WM,” he said.
In the single-center, prospective phase 2 study, researchers evaluated ibrutinib 420 mg once daily in 30 patients with WM. The median follow-up was 50 months.
The overall, major, and very good partial response (PR) rates were 100%, 87%, and 30%, respectively. The very good PR rate was numerically, though not significant, lower in patients with CXCR4 mutations than those without (14% vs 44%; P = 0.09). The median time to a minor response was 0.9 months, and to a major response was 1.9 months, though they were longer in those with mutated CXCR4 at 1.7 months (P = 0.07) and 7.3 months (P = 0.01).
Of the cohort, 6 patients had disease progression. The median progression-free survival (PFS) was not reached, and the 4-year PFS rate was 76%. There was also a non-significant lower 4-year PFS rate in patients with than without CXCR4 mutations (59% vs. 92%; P = 0.06).
Atrial fibrillation occurred in 20% of patients. The most common treatment-related adverse events were fatigue, upper respiratory infection, and hematoma.
