The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) is recommending that ibrutinib (Imbruvica) be approved to treat Waldenström’s macroglobulinemia (WM).
The CHMP is recommending the drug for use in WM patients who have received at least 1 prior therapy as well as previously untreated WM patients who are not suitable candidates for chemo-immunotherapy.
The European Commission will review this recommendation and should make a decision later this year.
Ibrutinib is already approved to treat WM in the US. The drug is also approved in the European Union, the US, and other countries to treat chronic lymphocytic leukemia and mantle cell lymphoma.
Janssen-Cilag International NV (Janssen) holds the marketing authorization for ibrutinib in Europe, and its affiliates market the drug in Europe and the rest of the world. In the US, ibrutinib is under joint development by Pharmacyclics and Janssen Biotech, Inc.
Phase 2 study
The CHMP’s recommendation for ibrutinib was based on a multicenter, phase 2 study in which researchers tested the drug in 63 patients with previously treated WM. Initial data showed an overall response rate of 87.3% in patients who received the drug for a median of 11.7 months.
Updated results from the study were published in NEJM in April. After a median treatment duration of 19.1 months, the overall response rate was 91%.
At 24 months, the estimated rate of progression-free survival was 69%, and the estimated rate of overall survival was 95%.
The most common grade 2-4 adverse events were neutropenia (22%) and thrombocytopenia (14%). Ibrutinib-related neutropenia and thrombocytopenia were reversible but required a dose reduction in 3 patients and treatment discontinuation in 4 patients.
Grade 2 or higher bleeding events occurred in 4 patients, and there were 15 infections considered possibly related to ibrutinib.
Treatment-related atrial fibrillation (AFib) occurred in 3 patients, all of whom had a prior history of paroxysmal AFib. AFib resolved when treatment was withheld, and all 3 patients were able to continue on therapy per protocol without an additional event.
