Dr. Dreyling on Key Safety Data from the TRIANGLE Trial in MCL

Martin Dreyling, MD, associate professor of medicine, University of Munich, head of the Lymphoma Program in the Department of Internal Medicine III, University Hospital of Munich (LMU), in Munich, Germany, discusses the key safety data from the phase 3 TRIANGLE trial (NCT02858258) in younger patients with mantle cell lymphoma (MCL).

Investigators evaluated the addition of ibrutinib (Imbruvica) to chemoimmunotherapy induction, followed by autologous stem cell transplant (ASCT) plus 2 years of ibrutinib maintenance vs chemoimmunotherapy and ASCT alone. A third arm also evaluated ibrutinib plus chemoimmunotherapy induction without ASCT, followed by ibrutinib maintenance. Induction therapy consisted of R-CHOP (rituximab [Rituxan], cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone) or R-DHAP (rituximab, dexamethasone, cytarabine, cisplatin).

Data from the study presented at the 2022 ASH Annual Meeting showed that the 3-year failure-free survival rate (FFS) was 72% with standard induction and ASCT alone compared with 88% for ibrutinib plus induction, ASCT, and ibrutinib maintenance (HR, 0.52; P = .0008).

Additionally, standard chemoimmunotherapy induction and ASCT failed to show superior FFS vs ibrutinib plus chemoimmunotherapy induction and 2-years of ibrutinib maintenance without ASCT. The 3-year failure-free survival rate was 72% for chemoimmunotherapy/ASCT vs 86% with ibrutinib without ASCT (HR, 1.77; P = .9979).

Because FFS and overall survival outcomes overlapped on the curves for the 2 experimental ibrutinib arms, evaluating safety was key to distinguish between the two regimens, Dreyling explains. Investigators found that the addition of ASCT to ibrutinib/chemoimmunotherapy induction and ibrutinib maintenance significantly increased toxicity, primarily for hematological adverse effects and also infections, Dreyling adds. Notably, safety data for ibrutinib induction and maintenance without ASCT was comparable to chemoimmunotherapy induction and ASCT alone, without the acute toxicity of transplantation, Dreyling continues.

Of the 3 treatment arms, the standard treatment with chemoimmunotherapy induction and ASCT alone was outperformed by both ibrutinib-containing arms, Dreyling says. Although investigators are still waiting for additional data to differentiate the 2 experimental arms, toxicity favors the ibrutinib arm without ASCT, which would represent a major shift in standard of care, Dreyling concludes.