Navigating Relapse and Sequencing Treatment After BTK Inhibitors in MCL

Peter Martin, MD, addressed the question of how to sequence subsequent lines of therapy for patients with mantle cell lymphoma (MCL) who have relapsed after initial Bruton tyrosine kinase (BTK) inhibitor treatment.

Martin navigated the current treatment void, noting that the field is rapidly moving BTK inhibitors to the frontline, leaving multiple questions for subsequent lines of treatment. He discussed 2 distinct scenarios for relapse and provided a thoughtful look at potential strategies, from retreatment with BTK inhibitors to the use of novel combinations.

Furthermore, he explores the emerging roles of CAR T-cells and bispecific antibodies, highlighting the need for oncologists to extrapolate from existing data as the MCL treatment paradigm continues its rapid evolution.

Martin is a professor of medicine and chief of the Lymphoma Program at Weill Cornell Medicine.

Transcript:

All the data we have currently for previously treated MCL is with BTK inhibitors in [patients] who have not received their prior BTK inhibitor. As we start to move BTK inhibitors from subsequent lines of therapy into the initial line of therapy, it opens this [mass] of questions: what do you do afterwards? There are a couple of different scenarios there. One is a scenario where somebody gets a BTK inhibitor, they’ve responded well, and the intention was to stop it to limit the exposure to the treatment and the [adverse] effects. We can assume that a retreatment strategy should be considered again with a BTK inhibitor that was initially successful, either alone or in combination. There are data that suggest that a BTK inhibitor plus a BCL-2 inhibitor can, in some ways, be superior to a BTK inhibitor alone.

The other question, though, is what to do in the setting of somebody who has received a BTK inhibitor…and has progressed in the context of that BTK inhibitor. Right now, it’s probably a bit of a guess in an extrapolation of data. If that were to happen in a second or third line of therapy setting, we would then move on to use CAR T-cells. There would certainly be a consideration of whether a bispecific antibody should factor in there. If somebody hasn’t received any chemotherapy, that’s an unknown. If somebody just gets a BTK inhibitor without chemotherapy, should there be a consideration for chemotherapy? We don’t have data there, so I don’t think I can answer that particular question. It's a good one, though.