Multinational phase 3 trial of addition of venetoclax to ibrutinib for relapsed or refractory mantle cell lymphoma

Ibrutinib (Ibr) is a BTK inhibitor approved in multiple countries for patients with previously treated mantle cell lymphoma (MCL). Venetoclax (Ven) is a BCL-2 inhibitor approved for patients with CLL and AML. Ibr and Ven have distinct and complementary mode of action, and the combination has shown promising results in early phase studies in MCL. The multinational phase 3 SYMPATICO study compared Ibr+Ven versus Ibr plus placebo (Pbo) for relapsed or refractory (R/R) MCL. The study found significantly improved investigator-assessed progression-free survival with Ibr+Ven compared with Ibr+Pbo. Ibr+Ven also significantly improved complete response rates (54% versus 32%) and time to next treatment (median not reached versus 35.2 months). At the current 51.2 months median follow-up, median overall survival was 44.9 months with Ibr+Ven versus 38.6 months with Ibr+Pbo. Grade ≥3 adverse events occurred in 84% of patients with Ibr+Ven and 76% of patients with Ibr+Pbo. The authors conclude that these results demonstrate a favorable benefit-risk proflie for Ibr+Ven in patients with R/R MCL.