Dr Dreyling on the Role of ASCT in Ibrutinib-Containing First-Line Therapy for Younger Patients With MCL

Martin Dreyling, MD, full professor, Department of Medicine, University Hospital LMU Munich, discusses updated results from the randomized phase 3 TRIANGLE trial (NCT02858258) conducted by the European MCL Network.

The study assessed the role of ASCT in the context of ibrutinib (Imbruvica)-containing first-line therapy for younger patients with mantle cell lymphoma (MCL). The analysis addressed questions regarding progression-free survival (PFS), overall survival (OS), and the post-induction roles of rituximab (Rituxan) maintenance and ASCT.

Data presented at the 2024 ASH Annual Meeting, demonstrated that 870 patients were randomly assigned to 1 of 3 treatment arms: chemotherapy plus ASCT (arm A; n = 288), chemotherapy plus ibrutinib and ASCT (A + I; n = 292), and chemotherapy plus ibrutinib without ASCT (I; n = 290). The study population had a median age of 57 years (range, 27-68), with 87% having stage IV disease and 58% classified as low risk by the Mantle Cell Lymphoma International Prognostic Index (MIPI).

At a median follow-up of 53 months, arm I demonstrated superior failure-free survival (FFS) compared with arm A (3-year FFS: 85% vs. 75%; two-sided p = 0.0102; hazard ratio [HR]: 1.38). FFS superiority of A+I over A was confirmed (3-year FFS: 86% vs. 75%; one-sided p = 0.0034; HR: 0.64), but FFS superiority of A+I over I was not established (3-year FFS: 86% vs. 85%; one-sided p = 0.28; HR: 0.87).

Overall survival (OS) was improved in arms I and A+I compared with arm A. The 3-year OS rates were 91% in arm I (p = 0.0041; HR: 0.59), 90% in arm A+I (p = 0.0069; HR: 0.61), and 85% in arm A.

Safety data indicated that autologous SCT provided no benefit for the overall population and was associated with higher toxicity. For the 10% of patients with high-risk features, including blastoid variants, high Ki-67 expression, or TP53 mutations, autologous SCT demonstrated potential benefit.

Dreyling noted that rituximab maintenance independently improved outcomes in all arms, and combining rituximab with ibrutinib maintenance emerged as the most effective post-induction strategy.

Dreyling concludes that ibrutinib-containing regimens significantly improve outcomes in younger patients with MCL, challenging the necessity of routine autologous SCT in this population. He emphasizes that ongoing studies are essential to further refine and personalize treatment strategies for this disease, particularly in identifying subgroups that may benefit most from SCT or other targeted approaches.