The FDA granted priority-review designation to the combination of ibrutinib and rituximab for the treatment of Waldenström macroglobulinemia (WM). The Bruton tyrosine kinase inhibitor ibrutinib is approved as a single agent for this indication.
The supplemental new drug application was supported by data from the phase III iNNOVATE trial, which included 150 patients with relapsed/refractory and treatment-naive WM. Patients were randomized to receive either 420 mg ibrutinib or placebo; all patients also received once-weekly 375 mg/m2 intravenous rituximab for four consecutive weeks, followed by rituximab administered every four weeks after a three-month interval.
At 30-month follow-up, the progression-free survival (PFS) rates among patients receiving the ibrutinib combination or placebo were 82 percent and 28 percent, respectively. The median PFS was not reached in the combination cohort, compared with 20.3 months in the placebo cohort (ranges not reported; hazard ratio [HR] = 0.20; 95% CI 0.11-0.38; p<0.0001).
Rates of adverse events (AEs) were similar in each group: All patients experienced at least one AE, and 45 and 46 patients (60% and 61%) in the combination and placebo arms, respectively, experienced a grade ≥3 AE. The most frequent grade ≥3 AEs to occur in the combination group compared with the placebo group included atrial fibrillation (12% vs. 1%; p value not reported) and hypertension (13% vs. 4%; p value not reported).
Sources: AbbVie press release, June 25, 2018; Dimopoulos MA, Tedeschi A, Trotman J, et al. Randomized phase 3 trial of ibrutinib/rituximab vs placebo/rituximab in Waldenström’s macroglobulinemia. Abstract #8003. Presented at the 2018 American Society of Clinical Oncology Annual Meeting, June 1, 2018; Chicago, IL.