Multinational phase 3 trial of ibrutinib plus venetoclax versus ibrutinib plus placebo for relapsed or refractory mantle cell lymphoma

The multinational phase 3 SYMPATICO study compared ibrutinib plus venetoclax versus ibrutinib plus placebo among patients with relapsed or refractory mantle cell lymphoma (R/R MCL) after one tot five previous lines of therapy and and ECOG performance status 0-2. The primary endpoint was investigator-assessed progression-free survival. The median progression-free survival was 31.9 months with ibrutinib-venetoclax versus 22.1 months with ibrutinib-placebo (HR 0.65; p=0.0052). The most common grade 3 or 4 adverse events were neutropenia (31% of patients in the ibrutinib-venetoclax group versus 11% of patients in the ibrutinib-placebo group), thrombocytopenia (13% versus 8%), and pneumonia (12% versus 11%). Serious adverse events occurred in 60% versus 60%, and treatment-related deaths in 2% versus 2%. The authors conclude that the combination of ibrutinib-venetoclax significantly improved progression-free survival compared with ibrutinib-placebo in patients with R/R MCL. The safety profile was consistent with known safety profiles of the individual drugs.