Ibrutinib (Imbruvica, Pharmacyclics) has become the first drug for the treatment of Waldenstrom's macroglobulinemia, a rare, indolent type of B-cell lymphoma, to be approved by the US Food and Drug Administration (FDA). The agency granted breakthrough therapy designation, priority review, and orphan product designation for the drug for this indication.
"Since the first description of Waldenstrom's macroglobulinemia more than 70 years ago, there has been no approved treatment for this cancer. Rather, doctors relied on therapies borrowed from similar cancers to treat these patients. I am truly grateful to the FDA for their thorough review and expedited approval of ibrutinib for this indication," said Steven P. Treon, MD, PhD, director of the Bing Center for Waldenstrom's Macroglobulinemia at the Dana-Farber Cancer Institute and associate professor at Harvard Medical School in Boston. He was principal investigator on the phase 2 trial that resulted in this approval.
This is an additional indication for ibrutinib, which is already approved for use in mantle cell lymphoma and chronic lymphocytic leukemia, in which it has been hailed as a "turning point" as it could spell the end of chemotherapy.
Ibrutinib has a novel mechanism of action. It is the first-in-class inhibitor of Bruton's tyrosine kinase, developed specifically for the treatment of B-cell cancers.
The FDA describes Waldenstrom's macroglobulinemia as a type of non-Hodgkin's lymphoma, which usually gets worse slowly over time. It causes B lymphocytes to grow within the bone marrow, lymph nodes, liver, and spleen. These 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 with the nervous system.
Ibrutinib works by blocking the enzyme that allows the abnormal B-cells in Waldenstrom's macroglobulinemia to grow and divide, the agency explains.
According to the National Cancer Institute, approximately 70,800 Americans were diagnosed and 18,990 died from non-Hodgkin's lymphomas in 2014.
Approval Based on Phase 2 Trial
The approval for the use of ibrutinib in Waldenstrom's macroglobulinemia was based on a phase 2 multicenter study conducted in 63 patients with previously treated disease (median age of 63 years) who took ibrutinib 420 mg once daily.
The overall response rate was 62%, as assessed by an Independent Review Committee using criteria adopted from the International Workshop on Waldenstrom's macroglobulinemia.
Nearly 51% of patients achieved a partial response (PR) and 11% achieved a very good PR, the manufacturer notes. No complete responses were reported. The median duration of response has not yet been reached (duration of response ranges from 1.8 to 2.8 months), the company said. The median time to response was 1.2 months (range, 0.7 - 13.4 months).
The most commonly occurring adverse reactions (reported by >20% patients) were neutropenia, thrombocytopenia, diarrhea, rash, nausea, muscle spasms, and fatigue, the company noted. Adverse events leading to dose reduction occurred in 11% of patients, and 6% of patients discontinued treatment due to adverse events.
The FDA adds that healthcare professionals should inform patients of the risk of bleeding (hemorrhage), infections, atrial fibrillation, development of new cancers (second primary malignancies), metabolic disturbances following treatment (tumor lysis syndrome), and embryo-fetal toxicity associated with the use of ibrutinib.
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Cite this: Ibrutinib Approved in US for Rare Lymphoma - Medscape - Jan 30, 2015.