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FDA Expands Imbruvica Label to Include Marginal-Zone Lymphoma
The FDA has approved ibrutinib (Imbruvica, Janssen Biotech/AbbVie) for the treatment of patients with relapsed/refractory marginal-zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti–CD20-based therapy. In the United States, ibrutinib now has five distinct indications: chronic lymphocytic leukemia, small lymphocytic lymphoma, Waldenström’s macroglobulinemia, previously treated mantle-cell lymphoma, and MZL.
MZL is a slow-growing B-cell lymphoma arising from lymphocytes at the edges of lymphoid tissue. It accounts for approximately 8% of all cases of non-Hodgkin’s lymphoma in adults, and the median age at diagnosis is 65 years.
The FDA’s decision was based on data from a phase 2, open-label, multicenter, single-arm study that evaluated the safety and efficacy of ibrutinib in MZL patients who required systemic therapy and had received at least one prior anti–CD20-based therapy. The efficacy analysis included 63 patients with the three subtypes of MZL: mucosa-associated lymphoid tissue (n = 32), nodal (n = 17), and splenic (n = 14).
The overall response rate (ORR) was 46%, as assessed by an independent review committee using the International Working Group criteria for malignant lymphoma, with efficacy observed across all three MZL subtypes. The median period to a response was 4.5 months (range, 2.3–16.4 months). In the study, 3.2% of patients had a complete response and 42.9% had a partial response. The median duration of responses was not reached.
The safety data from this study were consistent with the known safety profile of ibrutinib in B-cell malignancies. The most common adverse events included thrombocytopenia (49%), fatigue (44%), anemia (43%), diarrhea (43%), bruising (41%), musculoskeletal pain (40%), hemorrhage (30%), rash (29%), nausea (25%), peripheral edema and arthralgia (24% each), neutropenia (22%), cough (22%), dyspnea (21%), and upper respiratory tract infection (21%). The most common grade 3 or 4 adverse events included decreases in hemoglobin and neutrophils (13% each) and pneumonia (10%).
The new indication for ibrutinib was approved under accelerated approval based on the ORR, and continued approval may be contingent on the verification and description of clinical benefit in a confirmatory trial.
Source: AbbVie; January 19, 2017.