FDA expands approved use of Imbruvica for rare form of non-Hodgkin lymphoma

January 30, 2015

FDA has approved expanded use of ibrutinib for the treatment of Waldenstroms Macroglobulinemia.

FDA has approved expanded use of ibrutinib (ImbruvicaPharmacyclics and Janssen Biotech) for the treatment of Waldenstrom’s Macroglobulinemia (WM).

WM is a form of non-Hodgkin lymphoma (NHL), which is a type of cancer that begins in the body’s immune system. In WM, cancer cells grow mainly in the bone marrow and overtime cause abnormal blood cells, known as B lymphocytes (B-cells), to grow within the bone marrow, lymph nodes, liver and spleen. The defective B-cells make large amounts of a certain type of antibody known as immunoglobulin M, or IgM. The build-up of the antibody can lead to the symptoms associated with WM, including excess bleeding, problems with vision, and nervous system problems

Imbruvica works as a potent and irreversible inhibitor of Bruton’s tyrosine kinase (BTK), which is an important signaling molecule in the B-cell receptor pathway. Activation of B-cell receptor signaling is important for the survival of malignant B-cells. By inhibiting BTK, Imbruvica prevents malignant B-cell proliferation and survival.

Related: Study bolsters support of ibrutinib as second-line therapy in CLL treatment

FDA granted Imbruvica for WM breakthrough therapy designation, priority review, and orphan product designation and the drug’s new indication is being approved more than two months ahead of April 17, 2015, which was the date that the FDA was originally scheduled to complete review of the drug application.

The FDA had previously granted Imbruvica approval for use in patients with mantle cell lymphoma who received one prior therapy, for use in patients with previously treated chronic lymphocytic leukemia (CLL), as well as expanded its use to include treatment of CLL patients who carry a deletion in chromosome 17.

“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 FDA’s Center for Drug Evaluation and Research. “Continued research has discovered new uses of Imbruvica.”

FDA’s latest expansion of Imbruvica’s indications was based on a clinical study of 63 participants previously treated for WM. All participants received a 420 mg orally administered dose of Imbruvica daily until disease progression or side effects became intolerable; and results showed that 62% of participants had their cancer shrink after treatment.

Common side effects associated with the use of Imbruvica include thrombocytopenia, neutropenia, diarrhea, anemia, fatigue, bruising, upper respiratory tract infection, and rash. Healthcare professionals should also notify patients of the potential risks of bleeding, infections, abnormal heartbeat, secondary cancer development and metabolic disturbances following treatment.

Erin Bastick is a PharmD Candidate 2016, Ohio Northern University, Ada, Ohio, and an inpatient intern at University Hospitals, Cleveland.