Dr Dreyling on the Potential for Chemotherapy-Free Treatments in MCL

"BTK inhibitors are the cornerstone of treatment in mantle cell lymphoma [MCL]. Now, where [do] we go from here? The [TRIANGLE] study [data showed] that the addition of chemotherapy plus ibrutinib—in the United States, it’s likely the second-generation BTK inhibitors like acalabrutinib and zanubrutinib—is better than chemotherapy alone [in frontline MCL]. Now the question is if we can skip chemotherapy overall, and that’s the next study generation.”

Martin Dreyling, MD, full professor, Department of Medicine, University Hospital LMU Munich, discusses the clinical implications and future research directions for exploring chemotherapy-free frontline treatment options for patients with mantle cell lymphoma (MCL) following updated results from the randomized phase 3 TRIANGLE trial (NCT02858258).

TRIANGLE evaluated 3 regimens in younger patients with MCL: ibrutinib (Imbruvica) plus chemotherapy followed by autologous stem cell transplant (ASCT); ibrutinib plus chemotherapy without ASCT; and chemotherapy alone followed by ASCT. Findings presented at the 2024 ASH Annual Meeting showed an improvement in failure-free survival (FFS) for the 2 experimental regimens vs chemotherapy alone followed by ASCT. However, the omission of ASCT following ibrutinib plus chemotherapy did not lead to worse FFS outcomes.

Dreyling explains that although chemotherapy remains a backbone for the frontline treatment of patients with MCL, ongoing research is focusing on whether chemotherapy can be omitted without compromising efficacy for certain patient populations. Prior data have suggested that patients with low-risk MCL could achieve superior outcomes with ibrutinib plus rituximab (Rituxan) vs conventional chemotherapy. However, this was not the case for patients with intermediate- and high-risk MCL, Dreyling adds.

The European MCL Network is initiating 2 new randomized trials to further evaluate chemotherapy plus a BTK inhibitor vs novel non-cytotoxic regimens, Dreyling says. The next generation of clinical trials in MCL will be crucial in helping identify potential chemotherapy-free treatment options that could further alter the MCL treatment paradigm, he concludes.