FDA Expands Approved Use of Ibrutinib for Waldenström’s Macroglobulinemia

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The U.S. Food and Drug Administration (FDA) today expanded the approved use of ibrutinib (Imbruvica) for patients with Waldenström’s macroglobulinemia, a rare, indolent type of B-cell lymphoma. Ibrutinib is the first therapy indicated specifically for Waldenström’s macroglobulinemia and previously received Breakthrough Therapy designation for this use.

A type of non-Hodgkin lymphoma, Waldenström’s macroglobulinemia usually gets worse slowly over time and causes B lymphocytes to grow within the bone marrow, lymph nodes, liver, and spleen. The abnormal B cells also overproduce a protein known as immunoglobulin M or IgM (macroglobulin) that may lead to excess bleeding and problems with vision and the nervous system.

Ibrutinib works by blocking the Bruton’s tyrosine kinase that allows B cells in Waldenström’s macroglobulinemia to grow and divide.

“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. “Continued research has discovered new uses of [ibrutinib].”

The FDA initially granted ibrutinib accelerated approval in November 2013 for use in patients with mantle cell lymphoma who received one prior therapy. In February 2014, the FDA granted accelerated approval to ibrutinib for use in patients with previously treated chronic lymphocytic leukemia (CLL), and then in July 2014, expanded its use to include initial treatment of CLL patients who carry a deletion in chromosome 17p.

Phase II Study

The new approval was based on data from a phase II multicenter study of 63 previously treated patients with Waldenström’s macroglobulinemia. All study participants received a daily 420-mg dose of ibrutinib until disease progression or side effects became intolerable. Results showed 62% of participants had their cancer shrink after treatment (overall response rate). Nearly 51% of patients achieved a partial response, and 11% achieved a very good partial response. No complete responses were reported. At the time of the study, the duration of response ranged from 2.8 months to approximately 18.8 months.

The most common side effects associated with the drug are thrombocytopenia, neutropenia, diarrhea, anemia, fatigue, musculoskeletal pain, bruising, nausea, upper respiratory tract infection, and rash. Health-care professionals should inform patients of the risk for hemorrhage, infections, atrial fibrillation, second primary malignancies tumor lysis syndrome, and embryo-fetal toxicity associated with the use of ibrutinib.

According to the National Cancer Institute, approximately 70,800 Americans were diagnosed and 18,990 died from non-Hodgkin lymphomas in 2014. ■