Phase III SYMPATICO trial: Ibrutinib + venetoclax in nonblastoid MCL

Results from the open-label, first-line cohort of the phase III SYMPATICO (NCT03112174) trial evaluating first-line ibrutinib + venetoclax in patients, aged ≥65 years (n = 65) or aged ≥18 years with a TP53 mutation (TP53m; n = 11), with previously untreated nonblastoid mantle cell lymphoma (MCL) were published in Blood by Wang et al. The primary endpoint was complete response (CR) rate.

Key data: The CR rate was 69% (95% confidence interval [CI], 58–79) and the overall response rate (ORR) was 95% (95% CI, 87–99). Median progression-free survival (PFS) was 40.2 months, with a 3-year PFS rate of 59% (95% CI, 46–69). Median overall survival (OS) was not reached, and the 3-year OS rate was 79% (95% CI, 68–86). Outcomes were better in patients without vs those with TP53m (CR rate, 77% vs 55%; median PFS, 40.2 vs 22.0 months; 3-year OS rate, 86% vs 68%). The most common Grade ≥3 treatment-emergent adverse events (TEAEs) were neutropenia (29%), hypertension (12%), and neutrophil count decreased (10%); serious TEAEs occurred in 59% of patients. Adverse events (AEs) of special interest included atrial fibrillation (17%) and laboratory tumor lysis syndrome (TLS; 6%).

Key learning: In this trial, first-line ibrutinib + venetoclax demonstrated promising efficacy in patients with previously untreated nonblastoid MCL, supporting its potential as a treatment option for patients aged ≥65 years or aged ≥18 years with TP53m.