Prolonged follow-up of a phase 3 superiority trial of addition of ASCT to ibrutinib-containing first-line treatment for mantle cell lymphoma

First results of the multinational phase 3 superiority TRIANGLE trial, in 165 centers in 13 European countries and Israel, showed that adding ibrutinib to standard first-line immunochemotherapy improves failure-free survival (FFS) in patients aged 18-65 years with mantle cell lymphoma (MCL). Prolonged follow-up of the trial evaluated addition of autologous stem-cell transplantation (ASCT) to an ibrutinib-containing regimen. Patients with untreated, stage II-IV MCL and suitable for ASCT were randomized 1:1:1 to control group A (n=288) or experimental groups A + I (n=292) or I (n=290). Patients in group A received 6 alternating 21-day cycles of R-CHOP and R-DHAP or R-DHAOx, followed by ASCT. In group A + I, ibrutinib was added on days 1-19 of R-CHOP cycles and as 2-year maintenance after ASCT. In group I, ibrutinib was given in the same way, but ASCT was omitted. After median follow-up of 54.9 months, group A + I did not show FFS superiority over group I, but remained superior to group A, and group A did not show superiority over group I. Four-year overall survival (OS) was superior in group A + I versus group A and in group I versus group A. During maintenance or follow-up the most common grade 3-5 adverse events were hematological disorders (54% in group A + I, 28% in group I, and 23% in group A) and infections (34%, 26%, and 15%, respectively). The authors conclude that after a prolonged follow-up of 55 months, both ibrutinib containing groups showed relevant improvements not only in FFS but also in OS. In contrast, the addition of ASCT to an ibrutininb-containing regimen had no supplementary benefit but increased toxicity.