TRIANGLE phase III: Ibrutinib-containing first-line treatment with or without auto-HSCT for MCL

Results from the three-arm, randomized, open-label, phase III TRIANGLE trial (NCT02858258) evaluating ibrutinib-containing first-line treatment with or without autologous hematopoietic stem cell transplantation (auto-HSCT) in 870 patients aged 18–65 years with mantle cell lymphoma (MCL) were published in The Lancet by Dreyling et al. Eligible patients were randomized 1:1:1 to group I (n = 290), receiving ibrutinib + R-CHOP (rituximab + cyclophosphamide + doxorubicin + vincristine + prednisone)/R-DHAP/R-DHAOx (rituximab + dexamethasone + high-dose cytarabine + cisplatin/oxaliplatin) without auto-HSCT; group A+I (n = 292), receiving ibrutinib + R-CHOP/R-DHAP with auto-HSCT and 2 years of ibrutinib maintenance; or group A (n = 288), receiving R-CHOP/R-DHAP with auto-HSCT. The primary endpoint was investigator-assessed failure-free survival (FFS).

Key data: After a median follow-up of 54.9 months, group A+I did not demonstrate superior 4-year FFS vs group I (82% vs 81%; hazard ratio [HR], 0.86; p = 0.21). Ibrutinib-containing groups showed significantly improved 4-year overall survival (OS) vs group A (group A+I, 88% vs 81% [HR, 0.59; 95% CI, 0.38–0.92; p = 0.0036]; group I, 90% vs 81% [HR, 0.57; 95% CI, 0.36–0.90; p = 0.0019]). During the maintenance period or follow-up, Grade 3–5 hematologic adverse events (AEs) occurred in 54%, 28%, and 23% of patients, while infections occurred in 34%, 26%, and 15% of patients in groups A+I, I, and A, respectively.

Key learning: Ibrutinib, added to R-CHOP/R-DHAP induction, followed by 2 years of ibrutinib maintenance, represents a new standard of care for transplant-eligible patients aged ≤65 years with MCL. Auto-HSCT provided no additional efficacy benefit in the overall population but increased toxicity.