The U.S. Food and Drug Administration (FDA) has accepted for Priority Review a supplemental new drug application (sNDA) for ibrutinib (Imbruvica) in combination with rituximab (Rituxan) as a new treatment option for Waldenström's macroglobulinemia. If approved, the sNDA would expand the prescribing information of ibrutinib in Waldenström's macroglobulinemia beyond its current approved use as a single agent for all lines of therapy to include combination use with rituximab. As a single-agent therapy, ibrutinib—a first-in-class Bruton's tyrosine kinase (BTK) inhibitor—is the first and only FDA-approved treatment available for patients with Waldenström's macroglobulinemia.
“We are excited about the data from the phase III iNNOVATE study, which indicate that ibrutinib plus rituximab was able to improve progression-free survival vs rituximab alone across all lines of therapy and Waldenström's macroglobulinemia patient subgroups that were studied," said Thorsten Graef, MD, PhD, Head of Clinical Development at Pharmacyclics LLC, an AbbVie company. “These promising findings build on our commitment to exploring the full potential of ibrutinib alone and in combination with other treatments. If approved, this chemotherapy-free combination will provide another treatment opportunity for patients living with this rare disease, which continues to have very limited treatment options.”
The sNDA is supported by data from the phase III iNNOVATE (PCYC-1127) trial assessing ibrutinib in combination with rituximab vs rituximab alone in patients with previously untreated and relapsed or refractory Waldenström's macroglobulinemia. These data were recently presented at the 2018 ASCO Annual Meeting and simultaneously published by Dimopoulos in The New England Journal of Medicine.
iNNOVATE is a randomized, placebo-controlled, double-blind, phase III study, which enrolled 150 patients with relapsed/refractory and treatment-naive Waldenström's macroglobulinemia. Patients were randomized to receive intravenous rituximab 375 mg/m2 once weekly for 4 consecutive weeks, followed by a second 4-weekly rituximab course following a 3-month interval. All patients received either ibrutinib 420 mg or placebo once daily continuously until criteria for permanent discontinuation were met. The primary endpoint was progression-free survival, with secondary objectives including overall response rate, hematological improvement measured by hemoglobin, time-to-next treatment, overall survival, and number of participants with adverse events as a measure of safety and tolerability within each treatment arm.
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