Ibrutinib plus venetoclax in refractory mantle cell lymphoma

Results of the SYMPATICO trial, recently published on The Lancet Oncology, suggest a positive benefit–risk profile for ibrutinib plus venetoclax treatment in refractory mantle cell lymphoma.

SYMPATICO trial is a multicentre, randomised, double-blind, placebo-controlled, phase 3 study where 267 patients with pathologically confirmed relapsed or refractory mantle cell lymphoma after one to five previous lines of therapy where randomly assigned to receive ibrutinib-venetoclax or ibrutinib-placebo. After a median follow-up of 51.2 months, median progression-free survival was 31.9 months in the ibrutinib–venetoclax group and 22.1 months in the ibrutinib–placebo group. Secondary endpoints, such as complete response rate and time to next treatment, also significantly improved with ibrutinib–venetoclax treatment, whereas the overall response rate and overall survival (at interim analysis) were not statistically significant. The safety profile was consistent with known safety profiles of the individual drugs: serious adverse events occurred in 60% of both groups, treatment-related deaths occurred in 2% of both groups. As authors say, «Improvements in progression-free survival were generally robust across prespecified subgroups, including in the subgroup of patients with a TP53 mutation who have unmet medical needs. The venetoclax combination could represent a valuable chemo-free option for relapsed/refractory mantle cell lymphoma patients, prolonging remission duration and response quality over ibrutinib monotherapy. These data have the potential to change current practice for the treatment of patients with relapsed or refractory mantle cell lymphoma».