RCT: Adding Ibrutinib to immunochemotherapy and autologous stem-cell transplantation improves PFS in young mantle cell lymphoma patients but increases toxicity – The Lancet

Study Design and Population:

This study is a three-arm, randomized, open-label, phase 3 superiority trial named TRIANGLE, conducted across 165 centers in Europe and Israel. It aimed to compare the effectiveness of adding ibrutinib to standard immunochemotherapy, both with and without autologous stem-cell transplantation (ASCT), in 870 previously untreated mantle cell lymphoma patients aged 18-65 years, suitable for ASCT.

Main Findings:

After a median follow-up of 31 months, the arm with ibrutinib added to immunochemotherapy followed by ASCT (group A+I) demonstrated a 3-year failure-free survival rate of 88% compared to 72% in the standard immunochemotherapy plus ASCT group (group A). This indicates a significant improvement (hazard ratio 0.52; p=0.0008). Conversely, the efficacy of ASCT in the presence of ibrutinib (group A+I vs. group I, ibrutinib without ASCT) remains under analysis. Adverse events were more frequent and severe post-ASCT, particularly concerning hematological complications and infections.

Implications for Practice:

The results suggest that adding ibrutinib to first-line immunochemotherapy regimens significantly enhances clinical outcomes in younger patients with mantle cell lymphoma. However, the increased toxicity observed warrants careful patient monitoring, especially following ASCT. Further research is needed to evaluate the necessity and timing of ASCT in regimens containing ibrutinib.

Reference (link to free full-text):

Dreyling, M., et al. (2024). Ibrutinib combined with immunochemotherapy with or without autologous stem-cell transplantation versus immunochemotherapy and autologous stem-cell transplantation in previously untreated patients with mantle cell lymphoma (TRIANGLE): a three-arm, randomised, open-label, phase 3 superiority trial of the European Mantle Cell Lymphoma Network. The Lancet, 404(10184), 1938-1952. DOI: https://doi.org/10.1016/S0140-6736(24)00184-3.