Oral ibrutinib demonstrated durable single-agent efficacy in relapsed or refractory mantle-cell lymphoma in one study, and showed a high frequency of durable remissions in relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma in another project. The two reports, both funded in part by ibrutinib developer Pharmacyclics, were published online simultaneously by The New England Journal of Medicine.

Ibrutinib inhibits Bruton’s tyrosine kinase (BTK), which is implicated in the pathogenesis of B-cell cancers. An earlier phase 1 study demonstrated the antitumor activity of ibrutinib in several types of non-Hodgkin lymphoma, including mantle-cell lymphoma.

In the current work, a team led by Michael L. Wang, MD, of The University of Texas MD Anderson Cancer Center in Houston, Texas, administered a daily dose of ibrutinib 560 mg to 111 persons (median age 68 years) with relapsed or refractory mantle-cell lymphoma. The majority of recipients (86%) had intermediate-risk or high-risk disease based on clinical prognostic factors.

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The participants, who had received a median of three prior therapies, were divided into two groups: Members of one group had previously received at least two cycles of bortezomib therapy; members of the other group had received less or no prior bortezomib therapy.

Wang and colleagues recorded a response rate of 68% (75 patients), with a complete response rate of 21% and a partial response rate of 47%. Prior bortezomib therapy 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 most common adverse events were mild or moderate diarrhea, fatigue, and nausea. Hematologic events of grade 3 or higher were infrequent and included neutropenia in 16% of patients, thrombocytopenia in 11%, and anemia in 10%.

For the CLL investigation, John C. Byrd, MD, of The Ohio State University Comprehensive Cancer Center–Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC–James) in Columbus, Ohio, and fellow researchers conducted a phase 1b-2 multicenter study of 85 persons with relapsed or refractory CLL or small lymphocytic lymphoma. Most of the patients were considered to have high-risk disease.

Daily doses of oral ibrutinib at 420 mg (51 patients) or 840 mg (34 patients) yielded an overall response rate of 71% in each group. An additional 20% of the 420-mg recipients and 15% of the 840-mg recipients had a partial response with lymphocytosis. The response was independent of advanced-stage disease, number of previous therapies, and genomic risk factors (17p13.1 deletion).  

At 26 months, the estimated progression-free survival rate was 75% and the rate of overall survival was 83%.

Patients were able to receive extended treatment with minimal hematologic effects, as toxic effects were predominantly grade 1 or 2. They included transient diarrhea, fatigue, and upper respiratory tract infection.