Bruton's tyrosine kinase ( BTK ) is a mediator of the B-cell-receptor signaling pathway implicated in the pathogenesis of B-cell cancers.
In a phase 1 study, Ibrutinib ( Imbruvica ), a BTK inhibitor, showed antitumor activity in several types of non-Hodgkin's lymphoma, including mantle-cell lymphoma.
In this phase 2 study, researchers have investigated oral Ibrutinib, at a daily dose of 560 mg, in 111 patients with relapsed or refractory mantle-cell lymphoma.
Patients were enrolled into two groups: those who had previously received at least 2 cycles of Bortezomib ( Velcade ) therapy and those who had received less than 2 complete cycles of Bortezomib or had received no prior Bortezomib therapy.
The primary end point was the overall response rate. Secondary end points were duration of response, progression-free survival, overall survival, and safety.
The median age was 68 years, and 86% of patients had intermediate-risk or high-risk mantle-cell lymphoma according to clinical prognostic factors.
Patients had received a median of three prior therapies.
The most common treatment-related adverse events were mild or moderate diarrhea, fatigue, and nausea. Grade 3 or higher hematologic events were infrequent and included neutropenia ( in 16% of patients ), thrombocytopenia ( in 11% ), and anemia ( in 10% ).
A response rate of 68% ( 75 patients ) was observed, with a complete response rate of 21% and a partial response rate of 47%; prior treatment with Bortezomib had no effect on the response rate.
With an estimated median follow-up of 15.3 months, the estimated median response duration was 17.5 months, the estimated median progression-free survival was 13.9 months, and the median overall survival was not reached.
The estimated rate of overall survival was 58% at 18 months.
The study has revealed that Ibrutinib has shown durable single-agent efficacy in relapsed or refractory mantle-cell lymphoma. ( Xagena )
Wang ML et al, N Engl J Med 2013; 369:507-516