Once-daily ibrutinib and rituximab (IR) was superior to placebo and rituximab in terms of prolonging progression-free survival (PFS) and providing sustained hemoglobin improvements in patients with symptomatic Waldenstrom macroglobulinemia (WM), according to five-year follow-up data from the phase III iNNOVATE trial, which was presented at the 62nd American Society of Hematology Annual Meeting & Exposition.
The study, which was presented by Christian Buske, MD, of the University Hospital of Ulm in Germany, randomly assigned patients with confirmed symptomatic WM to either once-daily ibrutinib 420 mg with rituximab (n=75) or placebo plus rituximab (n=75). The endpoints of the study were PFS and response rates, overall survival (OS), hemoglobin improvement, and safety.
Over a median follow-up of 50 months, the median PFS in the IR arm had not been reached, whereas the median PFS in the placebo and rituximab arm was 20.3 months (P<0.0001). At the 54-month landmark timepoint, the PFS rates for IR as well as rituximab with placebo were 68% versus 25%, respectively.
The PFS benefit with IR versus placebo plus rituximab was observed in both treatment-naïve and previously treated patients. Additionally, the PFS benefit with IR was observed across patient subgroups, including baseline age, sex, serum immunoglobulin, hemoglobin, and International Prognostic Scoring System for WM.
A significantly greater proportion of major responses were observed in the IR arm (76% vs. 31%; P<0.0001). The overall response rates were 92% in the IR group versus 44% in the placebo arm (P<0.0001).
In addition, more patients who received IR experienced sustained hemoglobin improvements (77% vs. 43%; P<0.0001). The median OS was not reached in either arm, but the OS rates at the 54-month landmark timepoint were 86% with IR compared with 84% with rituximab and placebo.
The most common grade 3/4 adverse events in the study population included atrial fibrillation (AF), hypertension, neutropenia, and anemia. Approximately 75% of the 12 patients with grade 3/4 AF remained on treatment, and up to 45% of patients remained on treatment at time of study closure.