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ASCO 2026 | The current and future role of BTK inhibitors in DLBCL
Manali Kamdar, MD, University of Colorado Cancer Center, Denver, CO, comments on the potential of BTK inhibitors in diffuse large B-cell lymphoma (DLBCL), highlighting their role in certain groups of patients, particularly in those with non-germinal center B-cell–like (non-GCB) subtypes and in cases with central nervous system (CNS) relapse. Dr Kamdar also eagerly awaits the results of the Phase III ESCALADE study (NCT04529772), which is evaluating acalabrutinib plus R-CHOP in previously untreated non-GCB DLBCL. This interview took place during the 2026 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.
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Transcript
I am very optimistic about exploring BTK inhibitors in the right subset of diffuse large B-cell lymphoma. I think we do have some data coming out of the PHOENIX study that does establish that Ibrutinib plus R-CHOP, for example, in a certain subset, which is the non-GC, did extremely well compared to R-CHOP alone. So I’m looking forward to figuring out how to strategically manipulate BTK inhibition, whether in frontline or in the relapsed/refractory setting...
I am very optimistic about exploring BTK inhibitors in the right subset of diffuse large B-cell lymphoma. I think we do have some data coming out of the PHOENIX study that does establish that Ibrutinib plus R-CHOP, for example, in a certain subset, which is the non-GC, did extremely well compared to R-CHOP alone. So I’m looking forward to figuring out how to strategically manipulate BTK inhibition, whether in frontline or in the relapsed/refractory setting. I think BTK inhibitors are also very valuable in the fact that they can penetrate the blood-brain barrier. And with that, I think it’s important to highlight that MCD and C5 subtypes have a slightly higher predilection to having CNS relapses, we saw that at the ASCO meeting as well. And I think this is where we have immense therapeutic potential to explore these inhibitors a little bit more. So with relapsed diffuse large B-cell lymphoma, I still use a lot of BTK inhibition, especially if patients have CNS relapses and they are a non-GC subtype. I use a lot of BTK inhibitors if patients are dual exposed to CAR-T, CD20 bispecifics, and now have a non-GC phenotype of DLBCL. But I think I’m most excited about the ESCALADE study. The ESCALADE study is exploring acalabrutinib plus R-CHOP. It’s a randomized phase three study, and I think it may have a potential to further improve upon the existing survival rates that we have with newly diagnosed patients with DLBCL. So I’m eagerly looking forward to the ESCALADE study.
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