As reported in The Lancet by Martin Dreyling, MD, PhD, and colleagues, results in the European Mantle Cell Lymphoma Network phase III TRIANGLE trial indicate that the addition of ibrutinib to immunochemotherapy and autologous stem cell transplantation (ASCT) significantly improved failure-free survival in the first-line treatment of patients with mantle cell lymphoma aged ≤ 65 years.

Martin Dreyling, MD, PhD

Study Details

In the open-label trial, 870 patients from sites in 14 countries were randomly assigned 1:1:1 between July 2016 and December 2020 to receive either immunochemotherapy and ASCT (group A, n = 288), ibrutinib and immunochemotherapy and ASCT (group A+I, n = 292), or ibrutinib and immunochemotherapy without ASCT (group I, n = 290). Patients in all groups received induction immunochemotherapy with six alternating cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-DHAP (rituximab, dexamethasone, cytarabine, cisplatin). Group A+I and group I received ibrutinib at 560 mg daily on days 1 to 19 of R-CHOP cycles and as daily maintenance for 2 years.

The primary outcome measure of the trial was failure-free survival in the intention-to-treat population.

Failure-Free Survival

Median follow-up was 31 months. Failure-free survival at 3 years was superior in group A+I (88%, 95% confidence interval [CI] = 84%–92%) vs group A (72%, 95% CI = 67%–79%), with a hazard ratio of 0.52 (one-sided 98.3% CI = 0.00–0.86, P = .0008). Superiority of group A over group I was not shown, with 3-year failure-free survival of 72% (95% CI = 67%–79%) vs 86% (95% CI = 82%–91%) and a hazard ratio of 1.77 (one-sided 98.3% CI = 0.00–3.76, P = .9979). Comparison of group A+I vs group I is ongoing.

Adverse Events

No marked differences in grade ≥ 3 adverse events were observed during induction or ASCT between group A and group A+I. During maintenance or follow-up, grade ≥ 3 hematologic adverse events (50%) and infections (25%) were more common after ASCT plus ibrutinib (group A+I) compared with group I (28% and 19%, respectively) and group A (21% and 13%, respectively). Fatal infections occurred in 1% of patients in each group.

The investigators concluded, “Adding ibrutinib to first-line treatment resulted in superior efficacy in younger mantle cell lymphoma patients with increased toxicity when given after ASCT. Adding ibrutinib during induction and as maintenance should be part of first-line treatment of younger mantle cell lymphoma patients. Whether ASCT adds to an ibrutinib-containing regimen is not yet determined.”

Dr. Dreyling, of the Department of Medicine III, LMU University Hospital, Munich, is the corresponding author for The Lancet article.

Disclosure: The study was funded by Janssen and the Leukemia & Lymphoma Society. For full disclosures of the study authors, visit thelancet.com.