FDA Approves Ibrutinib for Mantle-Cell Lymphoma

The US Food and Drug Administration has approved ibrutinib (Imbruvica) for the treatment of patients with mantle-cell lymphoma (MCL), an aggressive and rare blood cancer, who have received at least one prior therapy. The new drug is an oral inhibitor of Bruton’s tyrosine kinase, a crucial signaling molecule in the B-cell receptor pathway that has been shown to cause cell death and to lower the rate of movement of cancerous B cells.

MCL accounts for about 6% of all non-Hodgkin lymphoma cases in the United States, often presenting at an advanced stage where the disease has spread to the lymph nodes, bone marrow, and other organs.

“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, in a press release. “The agency worked cooperatively with the companies to expedite the drug’s development, review, and approval, reflecting the promise of the Breakthrough Therapy Designation program.”

The trial that led to the accelerated approval of ibrutinib for MCL included 111 patients. Ibrutinib was administered daily until either disease progression or until adverse events became intolerable. Ibrutinib had an overall response rate of 66%. Improvement in survival has not yet been established.

Most of the adverse events in the trial were low-grade, including diarrhea, fatigue, nausea, anemia, neutropenia, edema, dyspnea, bruising, constipation, upper respiratory tract infection, rash, abdominal pain, vomiting, and decreased appetite. High-grade pneumonia occurred in 6% of patients. High-grade hematological events included thrombocytopenia and anemia. Four patients suffered from subdural hematomas, but all four patients had factors that put them at risk for such an event, including anticoagulant and antiplatelet therapies. Other adverse events include kidney problems, bleeding, infections, and the development of other cancer types.

Ibrutinib is the third drug approved to treat MCL. The FDA approved bortezomib in 2006 and lenalidomide in 2013.

Following the recent approval of obinutuzumab (Gazyva) for chronic lymphocytic leukemia, ibrutinib is now the second approved drug to have received a breakthrough therapy designation from the FDA. The designation can be used when preliminary evidence indicates a drug may offer a substantial improvement over current therapies for serious or life-threatening diseases.