A few days after the first drug with a breakthrough therapy designation was approved by the US Food and Drug Administration (FDA), ibrutinib (Imbruvica; Pharmacyclics/Janssen Biotech)—the second drug with such a designation—received an accelerated FDA approval for the treatment of patients with mantle-cell lymphoma (MCL), a rare form of non-Hodgkin lymphoma (NHL). MCL represents approximately 6% of all cases of NHL in the United States.
This aggressive type of cancer is usually diagnosed when it has already spread to the lymph nodes, bone marrow, and other organs. Ibrutinib is an oral Bruton’s tyrosine kinase inhibitor that blocks the activity of malignant B-cells.
Ibrutinib is indicated for use in patients with MCL who have received at least 1 previous therapy with bortezomib (Velcade) or with lenalidomide (Revlimid), the only 2 other drugs approved by the FDA for the treatment of patients with MCL.
Ibrutinib was approved under the FDA’s priority review path, and has received an orphan drug designation, by demonstrating its safety and efficacy in the treatment of MCL, which is considered a rare disease.
“Imbruvica’s approval demonstrates the FDA’s commitment to making treatments available to patients with rare diseases,” said Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.
The FDA’s accelerated approval of ibrutinib for MCL was based on a multicenter, single-arm trial of 111 patients who were previously treated for MCL; they received ibrutinib therapy daily until their disease progressed or their side effects became intolerable.
The results showed an overall response rate of 65.8% (95% confidence interval, 56.2-74.5); of these, 17% of the patients achieved complete response and 49% achieved partial response. The median duration of response was 17.5 months. The trial did not demonstrate an improvement in overall survival or in MCL-related symptoms.
The most common side effects reported included thrombocytopenia, diarrhea, neutropenia, anemia, fatigue, musculoskeletal pain, edema, upper respiratory infection, nausea, bruising, dyspnea, constipation, rash, abdominal pain, vomiting, and reduced appetite. Other clinically significant side effects include bleeding, infections, kidney problems, and the risk for developing other types of cancers.
