In an analysis reported in The Lancet, Dreyling et al provided long-term findings with three first-line regimens in the phase III TRIANGLE trial among patients aged 18 to 65 years with mantle cell lymphoma.
Study Details
In the international (13 European countries and Israel) open-label trial, 870 patients with untreated stage II to IV disease suitable for autologous stem cell transplantation (ASCT) were randomly assigned 1:1:1 between July 2016 and December 2020 to:
- Control group A (n = 288), with treatment consisting of six alternating 21-day cycles of R-CHOP and R-DHAP or R-DHAOx, followed by ASCT
- Experimental treatment A+I group (n = 292), with treatment consisting of the addition of ibrutinib on days 1 to 19 of R-CHOP cycles and as 2-year maintenance after ASCT
- Experimental treatment I group (n = 290), with treatment consisting of the addition of ibrutinib with no ASCT.
The initial results from the trial showed that adding ibrutinib to standard first-line immunochemotherapy improved failure-free survival.
Key Findings
Median follow-up was 54.9 months (95% confidence interval [CI] = 54.4–56.0 months).
Group A+I did not show superiority over group I, with a 4-year failure-free survival of 82% (95% CI = 78%–87%) vs 81% (95% CI = 76%–86%; hazard ratio [HR] = 0.86, 98.33% CI = 0.00–1.27, P = .21). Group A+I was superior to group A (70%, 95% CI = 65%–76%; HR = 0.63, 98.33% CI = 0.00–0.89, P = .0026). Group A did not show superiority over group I (HR = 1.45, 98.33% CI = 0.00–2.02, P = .99).
Overall survival at 4 years was 88% (95% CI = 84%–92%) in group A+I vs 81% (95% CI = 76%–85%) in group A (HR = 0.59, 95% CI = 0.38–0.92, P = .0036), and 90% (95% CI = 87%–94%) in group I (HR vs group A = 0.57, 95% CI = 0.36–0.90, P = .0019).
During maintenance or follow-up, the most common grade 3 to 5 adverse events were hematologic disorders, occurring in 54% of group A+I vs 28% of group I and 23% of group A, and infections, occurring in 34%, 26%, and 15% of patients, respectively.
The investigators concluded: “After a prolonged follow-up of 55 months, both ibrutinib-containing groups showed relevant improvements not only in failure-free survival—a modified form of progression-free survival—but also in overall survival. In contrast, the addition of ASCT to an ibrutinib-containing regimen had no supplementary benefit but increased toxicity. Induction treatment with ibrutinib and R-CHOP plus R-DHAP (or R-DHAOx), followed by 2 years of maintenance treatment with ibrutinib, should be considered as a new standard of care for younger patients with mantle cell lymphoma.”
Martin Dreyling, MD, PhD, of the Department of Medicine III, LMU University Hospital, Munich, Germany, is the corresponding author for The Lancet article.
DISCLOSURE: The study was funded by Janssen. For full disclosures of the study authors, visit thelancet.com.
