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SOHO 2025 | Treating MCL after covalent BTKi: CAR T-cells, non-covalent BTKi, antibody-drug conjugates, & more
Krish Patel, MD, Sarah Cannon Research Institute, Nashville, TN, shares insights into the treatment of mantle cell lymphoma (MCL) after it has progressed following therapy with a covalent BTK inhibitor (BTKi). Dr Patel notes that emerging tools, such as CD19 autologous CAR T-cells, non-covalent BTKis, bispecifics, and antibody-drug conjugates, offer new hope for patients. This interview took place at the 13th Annual Meeting of the Society of Hematologic Oncology (SOHO 2025) in Houston, TX.
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Transcript
So we know that BTK inhibitors have really been a huge asset in mantle cell lymphoma. We see the shift now from second line into first line. But we also know that outcomes after progression on a covalent BTK inhibitor have historically been very poor. And there’s a number of reasons for that. We see enrichment of a lot of adverse mutations and so there’s a shift in biology...
So we know that BTK inhibitors have really been a huge asset in mantle cell lymphoma. We see the shift now from second line into first line. But we also know that outcomes after progression on a covalent BTK inhibitor have historically been very poor. And there’s a number of reasons for that. We see enrichment of a lot of adverse mutations and so there’s a shift in biology. The tools we have today are CD19 autologous CAR T-cells and pirtobrutinib, which is a non-covalent BTK inhibitor. And these are fabulous tools, but we need more. CAR T-cells are not available to all patients. Pirtobrutinib is really a drug that has a binary response, so people either respond really well or they don’t respond. So what we’re starting to see now are the development of more bispecifics, ADCs, things that we can really reach for off the shelf because progression after covalent BTK inhibitor in mantle cell tends to be very rapid and so we really need to be able to deliver therapy very quickly. So I think we’re going to see more combinations of those agents as well mixing ADCs with maybe non-covalent BTK inhibitors and then lastly we also have this class of BTK degraders which we’ve seen great activity for in CLL we’re starting to see some of that in mantle cell lymphoma also.
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