Dr Martin on the Role of BTK Inhibitors in the Management of MCL

A lot of questions have been answered over the past decade but we’re left with even more questions. [BTK inhibitors] work well as single agents in the second-line setting but we can do better, and combination strategies are likely to be that way forward.”

Peter Martin, MD, associate professor, medicine, chief, Lymphoma Program, Weill Cornell Medicine, discusses ongoing challenges and emerging strategies regarding the role of BTK inhibitors in the treatment of patients with mantle cell lymphoma (MCL). Martin shared these insights during the 42nd Annual Chemotherapy Foundation Symposium.

In his presentation, Martin explained how BTK inhibitors, such as ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa), have transformed the treatment paradigm for MCL, particularly in the second-line setting, Martin explains. These agents are effective as single agents in patients with relapsed disease but are not curative, leaving room for improvement, he adds. Combination approaches may represent a way forward to enhance outcomes, particularly in high-risk disease subsets such as blastoid MCL and TP53-mutated MCL, where single-agent BTK inhibitors provide limited benefit, Martin says.

In high-risk MCL, adding agents such as venetoclax (Venclexta), lenalidomide (Revlimid), or rituximab (Rituxan) to BTK inhibitors has shown promise, Martin continues. However, these combinations are associated with increased risks of adverse effects, raising concerns about tolerability and quality of life (QOL) for patients, he notes. Identifying which patients will derive the most benefit from these intensified regimens remains a critical area of research, Martin explains.

For patients with lower-risk MCL, BTK inhibitors in combination with other agents may enhance efficacy but require careful consideration of long-term QOL impacts due to prolonged treatment durations, Martin continues. Developing personalized, risk-adapted strategies is essential to balance efficacy with tolerability in this population, he says.

Sequencing strategies for BTK inhibitors also remain an unmet need, Martin notes. Whether BTK inhibitors should be used earlier in treatment, combined with other agents, or reserved for specific patient subsets requires further investigation, he says. Additionally, the integration of newer modalities, such as CAR T-cell therapy or bispecific antibodies, alongside BTK inhibitors is an emerging area of interest, according to Martin.