How to treat MCL that is refractory to BTK inhibitors

During the Lymphoma Hub Steering Committee meeting, Martin Dreyling, Ludwig-Maximilians-Universität, Munich, DE, chaired a discussion on, How to treat mantle cell lymphoma (MCL) that is refractory to Bruton’s tyrosine kinase (BTK) inhibitors. This discussion also featured Gilles Salles, Francesc Bosch, Grzegorz Nowakowski, and Michael Dickinson.

Dreyling begins with providing an overview of regional MCL treatment guidelines and highlighted the treatment challenges in early and late relapses. In German, Austrian, and Swiss guidelines, the addition of BTK inhibitors is standard for younger patients, challenging the previous standard of care of autologous transplant. Treatment challenges vary based on the timing of relapse. For instance, late relapses provide greater flexibility in treatment options, whereas early relapses pose difficulties due to limited approved therapies.

The panel then delved into the challenges of treating patients with MCL who relapse after BTK inhibitor therapy by emphasizing the importance of tailoring treatment strategies based on disease biology, relapse timing, and patient factors such as age and comorbidities. Treatment approaches often include continuing BTK inhibitor therapy even after disease progression to manage accelerated disease. For fit patients, CAR T-cell therapies are a viable option, while bispecific antibodies are emerging as promising alternatives. Regional differences further complicate treatment. In Australia, limited access to frontline BTK inhibitors has increased reliance on clinical trials and therapies such as CAR T-cells and bispecific antibodies. Conversely, in the United States, CAR T-cell therapies are beneficial for fit but not frail patients who have not previously received them.

The discussion underscored the complexity of managing MCL that is refractory to BTK inhibitors, as well as the need for personalized approaches informed by regional availability and patient-specific considerations.