FDA Expands Approval of Ibrutinib to Waldenström’s macroglobulinemia

Richard Pazdur, MD

The FDA has expanded the approval of ibrutinib (Imbruvica) for the treatment of patients with Waldenström’s macroglobulinemia (WM). This approval represents the first in WM and comes more than two months ahead of its Prescription Drug User Fee Act (PDUFA) deadline of April 17.

The decision was based on a phase II study of 63 patients who received 420 mg ibrutinib once daily. The overall response rate on the trial was 62%, according to an independent review committee. Responses ranged from 2.8 to 18.8 months, though a median has not yet been reached.

“Today’s approval highlights the importance of development of drugs for supplemental indications,” Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research, said in a statement. “Continued research has discovered new uses of Imbruvica.”

In the study, 63 patients with relapsed/refractory WM received 420 mg/day oral ibrutinib for up to 2 years until disease progression or unacceptable toxicity. At baseline, patients’ mean hemoglobin level was 10.5 mg/dL and mean serum IgM level was 3610. Anemia was the most common reason for treatment initiation (87.3% of patients).

In total, 11% of patients had very good partial responses and 51% had partial responses. According to data presented at the 2013 ASCO Annual Meeting, the best overall response rate (minor response or better using consensus criteria adapted from the 3rd International Workshop on WM) was 83% following a median of 9 cycles.

The most common adverse events observed on the trial were neutropenia, thrombocytopenia, diarrhea, rash, nausea, muscle spasms, and fatigue. Adverse events led to dose reduction in 11% of patients and discontinuation in 6% of patients.

"Because there has never been an FDA-approved treatment for Waldenstrom's macroglobulinemia since it was first identified over 70 years ago, doctors had to rely on therapies borrowed from similar cancers to treat these patients," Steven P. Treon, MD, PhD, lead investigator of the trial and director of the Bing Center for Waldenstrom's Macroglobulinemia at the Dana-Farber Cancer Institute, said in a statement.

Ibrutinib is jointly developed and commercialized by Janssen Biotech Inc. and Pharmacyclics. This is the fourth indication for the agent. Ibrutinib is also approved for patients with chronic lymphocytic leukemia (CLL) with a 17p deletion, patients with CLL who had received at lease one prior treatment, and patients with mantle cell lymphoma who have received at least one prior treatment. The agent received a breakthrough therapy designation for WM in February 2013.

In 2014, approximately 70000 patients were diagnosed with non-Hodgkin lymphomas. WM is a rare form of non-Hodgkin lymphoma. Approximately 1000-1500 patients in the US are diagnosed with WM each year, according to the FDA.