On November 13, 2013, the U. S. Food and Drug Administration granted accelerated approval to Ibrutinib (IMBRUVICA, Pharmacyclics, Inc.) for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.
The approval was based on the results of a multi-center, international, single-arm trial enrolling 111 patients with previously treated mantle cell lymphoma. The primary endpoint was overall response rate (ORR).
The efficacy results demonstrated a 66% ORR (95% CI 56.2, 74.5). Seventeen percent of patients achieved complete responses, and 49% achieved partial responses. The median response duration was 17.5 months (95% CI 15.8, not reached).
Safety was evaluated in the 111 patients with previously treated MCL who received ibrutinib 560 mg daily. The most common adverse reactions reported in the clinical trial (occurring in greater than or equal to 20% of patients) were thrombocytopenia, diarrhea, neutropenia, anemia, fatigue, musculoskeletal pain, peripheral edema, upper respiratory infection, nausea, bruising, dyspnea, constipation, rash, abdominal pain, vomiting, and decreased appetite.
Five percent of patients had grade 3 or higher bleeding events (subdural hematoma, gastrointestinal bleeding, and hematuria). Bleeding events, including bruising of any grade, occurred in 48% of patients. Treatment-emergent grade 3 or 4 cytopenias occurred in 41% of patients. Twenty-five percent had grade 3 or higher infections.
As a condition of this accelerated approval, FDA required that the sponsor submit 24-month follow-up data for all patients in the single-arm trial and submit the results of a randomized controlled trial comparing ibrutinib in combination with bendamustine plus rituximab to bendamustine plus rituximab in patients with newly diagnosed MCL.
The recommended dose and schedule for ibrutinib is 560 mg (four 140 mg capsules) taken orally once daily.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm
, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).