Ibrutinib Prolongs PFS, Leads to Sustained Hemoglobin Improvements in Patients With Waldenstrom’s Macroglobulinemia

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’s macroglobulinemia (WM), according to 5-year follow-up data from the phase 3 iNNOVATE trial presented at the 62^nd American Society of Hematology Annual Meeting and 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 period 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% and versus 25%, respectively.

The PFS benefit with IR versus placebo plus rituximab was observed in patients who were both treatment naïve and patients who were previously treated. Additionally, the PFS benefit with IR was observed across patient subgroups including baseline age, sex, serum immunoglobulin, hemoglobin, and International Prognostic Scoring System for Waldenström Macroglobulinemia.

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.

https://ash.confex.com/ash/2020/webprogram/Paper134460.html