Dr Dreyling on the Rationale Behind the TRIANGLE Study in MCL

"We examined the most effective salvage treatments for relapsed mantle cell lymphoma and, based on a nonrandomized data set, identified BTK inhibitors (BTKis) as the most potent approach. Consequently, we incorporated BTKis into first-line treatment, comparing the traditional standard of care—including ASCT—with two experimental arms."

Martin Dreyling, MD, full professor in the Department of Medicine at the University Hospital LMU Munich, discusses the rationale for the randomized phase 3 TRIANGLE trial (NCT02858258), which evaluated the role of ibrutinib (Imbruvica) in combination with chemotherapy and rituximab (Rituxan) with or without autologous stem cell transplant (ASCT) vs chemoimmunotherapy and ASCT alone for in previously untreated patients with mantle cell lymphoma (MCL).

The study aimed to determine whether incorporating ibrutinib into first-line therapy could improve outcomes compared with the conventional approach of induction chemotherapy followed by ASCT and rituximab maintenance. Investigators sought to assess whether ibrutinib could enhance treatment efficacy when added to ASCT or potentially replace ASCT altogether. The trial included three arms: standard induction chemotherapy with ASCT and rituximab maintenance (arm A); induction chemotherapy plus ibrutinib followed by ASCT and rituximab maintenance (arm A+I); and a novel regimen of chemotherapy plus ibrutinib without ASCT (arm I).

The rationale for the trial was based on evidence supporting the role of cytarabine-based induction and rituximab maintenance in improving long-term disease control, Dreyling explains. Additionally, ibrutinib had previously demonstrated efficacy in relapsed/refractory MCL, prompting investigation into its integration into first-line therapy. TRIANGLE aimed to establish whether an ibrutinib-containing regimen could offer comparable or superior efficacy while reducing the treatment burden associated with ASCT.

By comparing these strategies, the trial sought to clarify whether ASCT remains necessary in the era of targeted therapy, particularly for patients who might achieve durable remissions with chemotherapy, rituximab, and ibrutinib alone.