David Green, MD, PhD

Patients with refractory or relapsed disease achieved a relatively high response rate with few adverse effects.

Ibrutinib is an oral, covalent inhibitor of Bruton's tyrosine kinase, a mediator of B-cell receptor signaling implicated in lymphomagenesis. Mantle-cell lymphoma (MCL) is an aggressive tumor that often relapses after initial responses to chemotherapy. Is there a role for ibrutinib in patients with refractory or relapsed MCL?

To find out, investigators conducted an industry-funded, multicenter, phase II trial in which 111 previously treated MCL patients received ibrutinib (560 mg per day). Results were as follows:

• Ibrutinib was well tolerated; most adverse events (diarrhea in 50%, fatigue in 41%) were low grade. Grade 3 and 4 hematologic toxicity included neutropenia (16%), thrombocytopenia (11%), and anemia (10%).
• Grade 3 infections occurred in 22% and bleeding in 5%; however, almost all major bleeds were associated with trauma or antithrombotic therapy.
• Adverse events led to discontinuation of treatment in 7%. Death occurred in 14%, mostly due to disease progression.
• The overall response rate (the primary outcome) for all patients was 68% (21% complete, 47% partial). The median time to a response was 1.9 months, and the estimated response duration was 17.5 months.
• The estimated median progression-free survival was 13.9 months, and estimated overall survival rate was 58% at 18 months.
• MCL cells increased in the peripheral blood 10 days after initiation of ibrutinib therapy, and then declined to near baseline by day 28.

Citation(s):

Wang ML et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med 2013 Jun 19; [e-pub ahead of print].