Interim results of a phase 2 study demonstrated the durability of responses and confirmed the “unprecedented” single-agent activity of ibrutinib in relapsed or refractory mantle cell lymphoma (MCL) in terms of overall response rate, according to research presented at the annual meeting of the American Society of Hematology (ASH), held in Atlanta, Georgia, December 8-11, 2012.

Ibrutinib, an inhibitor of Bruton’s tyrosine kinase, acts against malignant B-cells. MCL is a rare and aggressive B-cell subtype of non-Hodgkin lymphoma, accounting for 6% of non-Hodgkin cases. Although response rates to initial therapy for MCL are high, patients often relapse due to acquired chemotherapy resistance and short response durations to conventional therapy.

In the current study, a team led by Michael Wang, MD, of the Departments of Lymphoma/Myeloma and Stem Cell Transplantation/Cellular Therapy at The University of Texas MD Anderson Cancer Center in Houston, Texas, evaluated the efficacy of ibrutinib in 109 patients with relapsed or refractory MCL. Among the patients, median age was 68 years, median time since diagnosis was 42 months, and median number of prior treatments was three. The majority (77%) had stage IV disease. The participants received 560 mg/day of oral ibrutinib in continuous 28-day cycles until disease progression.

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At median follow-up of 9.2 months, overall response rate was 68% and complete remission rate was 22%. Median time to partial response was 2 months, median time to complete remission was 4 months, and median time on treatment was 6 months. At the time these results were reported at the ASH meeting, 53% of the patients remained on treatment.

The investigators noted even more dramatic results among the 51 people who had been enrolled in the study the longest. In this subgroup, median time on study treatment was 15 months, overall response rate was 75%, and complete remission rate was 39%.

In the abstract they presented at the ASH meeting, Wang and colleagues described the single-agent activity of ibrutinib as “unprecedented” in terms of overall response rate in relapsed or refractory MCL. In a separate statement issued by MD Anderson, Wang himself commented, “I believe we are witnessing a breakthrough in mantle cell lymphoma.” He added that in a heavily treated relapsed or refractory population, oral ibrutinib induced a response rate as high as 70%—”better than any other single agent ever tested in MCL,” with a durable response and long progression-free survival.

Side effects were mostly minor, including diarrhea, fatigue, upper respiratory tract infections, nausea, and rash. Grade 3 or higher adverse effects included low white-blood-cell counts, anemia, and diarrhea. Grade 4 treatment-related adverse effects included neutropenia in 5% of patients, hyperuricemia in 2%, and pancytopenia in 1%. One grade 5 adverse effect, a case of pneumonia, was thought to be treatment-related.