FDA Approves Ibrutinib for Waldenström Macroglobulinemia

Ibrutinib had already been approved for both mantle cell lymphoma and chronic lymphocytic leukemia

The US Food and Drug Administration (FDA) expanded the approved use of ibrutinib (Imbruvica) earlier today to include patients with Waldenström macroglobulinemia, a rare form of non-Hodgkin lymphoma that develops slowly and causes abnormal B cells to grow within the lymph nodes, bone marrow, spleen, and liver.

“Today’s approval highlights the importance of development of drugs for supplemental indications,” 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. “Continued research has discovered new uses of Imbruvica.”

The single-arm, multicenter trial that led to the expanded approval included 63 patients with previously treated Waldenström macroglobulinemia. Study participants received a daily 420 mg dose of oral ibrutinib until disease progression or unacceptable toxicity.

The study found that ibrutinib produced an overall response rate of 62% (no complete responses were achieved). The median time to response was 1.2 months. The median response duration was not reached, though responses ranged from 2.8 months to 18.8 months.

Adverse events among patients in the trial include nausea, diarrhea, anemia, fatigue, thrombocytopenia, neutropenia, rash, bruising, musculoskeletal pain, and upper respiratory tract infection.

Patients should be informed of the risk of hemorrhage, infections, atrial fibrillation, embryo-fetal toxicity, tumor lysis syndrome, and second primary malignancies.

Approximately 70,800 new cases of non-Hodgkin lymphoma were diagnosed in 2014 in the United States, according to the National Cancer Institute, with Waldenström macroglobulinemia comprising about 1,000 to 1,500 of these cases.

The abnormal B cells in patients with Waldenström macroglobulinemia also overproduce immunoglobulin M, which can lead to bleeding, vision problems, and symptoms of nervous system involvement.

Ibrutinib is a selective and covalent inhibitor of the Bruton tyrosine kinase enzyme, an enzyme that allows abnormal B cells to grow and divide.

The FDA first approved ibrutinib for the treatment of patients with mantle cell lymphoma in November 2013. The drug was approved to treat patients with chronic lymphocytic leukemia (CLL) in February 2014. In July 2014, this approval was expanded to include CLL patients who carry a deletion in chromosome 17.

Data presented at the 2014 American Society of Hematology (ASH) Annual Meeting found that ibrutinib shows activity in multiple myeloma.