Dr Dreyling on the Expanding Role of BTK Inhibitors in the Treatment of 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? That’s the next study generation.”

Martin Dreyling, MD, full professor in the Department of Medicine at University Hospital LMU Munich, discussed the expanding role of BTK inhibitors in the treatment of mantle cell lymphoma (MCL) and the potential for chemotherapy-free regimens to redefine future therapeutic approaches in the frontline setting.

BTK inhibitors have emerged as a cornerstone in the management of MCL, and updated data have supported their integration into frontline strategies, Dreyling said. Although the combination of BTK inhibitors such as ibrutinib (Imbruvica) with chemotherapy has demonstrated improved outcomes compared with chemotherapy alone, current research efforts are increasingly focused on the potential to omit cytotoxic agents entirely. This shift reflects a growing interest in non-cytostatic, targeted strategies for select patient populations.

The European MCL Network is initiating 2 randomized clinical trials to further investigate the comparative effectiveness of chemoimmunotherapy plus a BTK inhibitor vs fully targeted, chemotherapy-free regimens. These trials aim to determine whether non-cytotoxic combinations could deliver durable disease control with minimal toxicity, particularly for biologically favorable MCL subsets.

Dreyling emphasized that the next generation of MCL trials will be critical in refining risk-adapted strategies and identifying patients who may safely forgo chemotherapy. These studies are expected to inform a new standard of care by exploring the feasibility and efficacy of fully targeted treatment platforms in MCL.