Prior reports have indicated that the combination of ibrutinib and rituximab showed sustained responses and a manageable toxicity profile in rituximab-refractory Waldenström’s macroglobulinemia (Dimopoulos MA, et al. Lancet Oncol. 2016). Here, researchers present follow-up findings from the phase 3 iNNOVATE study.
There were 3 treatment arms in the study. Patients in the randomized part of the trial received prior rituximab therapy and required a response to their last rituximab-based regimen. These patients were randomized to either daily 420 mg of ibrutinib plus rituximab (IR) or placebo plus rituximab (R) at a dose of 375 mg/m2 per week intravenously at weeks 1 to 4 and 17 to 20. In an open-label substudy, patients who failed to achieve a minor response or better, or relapsed within 12 months of their last rituximab-containing therapy, received daily 420 mg of ibrutinib until disease progression or unacceptable toxicity.
With extended follow-up and a median duration of treatment of 33.4 months, overall response rates (ORRs) were 95% with IR versus 48% with R (P <.0001), respectively. With continued IR treatment, 25% of patients achieved a very good partial response compared with only 3% in the R arm. Median progression-free survival (PFS) was not reached with IR versus 20.3 months with R (hazard ratio, 0.22 [0.12-0.39]; P <.0001). At 36 months, PFS was 76% for patients receiving IR treatment versus 31% for R. The 36-month overall survival (OS) rates were 93% for IR and 90% for R, a nonsignificant difference.
Completion of treatment was 93% among patients receiving IR compared with 71% in patients receiving R. Overall, grade ≥3 adverse events (AEs) occurred in 49% of patients in the IR arm and 42% in the R arm.
In the open-label substudy, 31 patients received single-agent ibrutinib. In this group, with longer follow-up, median PFS was 41 months, estimated 36-month PFS was 61%, ORR was 90%, and estimated 36-month OS was 84%. Median duration of ibrutinib treatment was 38.4 months, with no major hemorrhagic or atrial fibrillation events reported. Grade ≥3 AEs occurred in 77% of patients; however, no fatal AEs were reported.
Researchers concluded that IR showed continued superiority over R in treatment-naïve and previously treated patients with Waldenström’s macroglobulinemia, regardless of genotypic factors. In both relevant study arms, ibrutinib had a manageable safety profile and no new safety signals were identified with longer follow-up.
Buske C, et al. ASH 2018. Abstract 149.