EHA 2026 | Emerging BTK inhibitor combination strategies being explored in CLL

Certainly, in chronic lymphocytic leukemia, the novel doublets are very interesting, very effective. Acalabrutinib plus venetoclax has been approved in treatment of previously untreated CLL. Zanubrutinib is being investigated in combination with another BCL2 inhibitor, sonrotoclax, in CLL, in a frontline setting in a randomized study. I do believe we can anticipate high efficacy of that regimen as well, followed by hopefully regulatory approvals. There are also interesting studies employing pirtobrutinib. At this EHA, there is data which show high efficacy of pirtobrutinib, venetoclax, rituximab in relapsed CLL setting. So that is a regimen which I think some of us will start using more frequently in the future. So the doublets and triplets with BCL2 inhibitor CD20 antibodies is certainly where the field is moving, also them being time-limited therapies. And would be interested to see some data with bispecific antibody combinations. There are some studies in Germany which are combining BTK inhibitor pirtobrutinib with epcoritamab in Richter’s. So there is still a lot of work to be done with those. And, you know, in the field of CAR-T, CAR T-cell therapy still is, by itself, seems to be maybe a bit too toxic, maybe a bit less efficacy than we would like in chronic lymphocytic leukemia, specifically talking about liso-cel. But we did an analysis, retrospective analysis of real-world efficacy of liso-cel. And it seems higher than in the original study, actually. And I think that is in part because in many instances, liso-cel has been actually given together with pirtobrutinib or other BTK inhibitors. So there is clearly a combination effect there. So that needs to be studied as well, as I think that would be one way to improve efficacy of CAR T-cells in CLL. So a lot of exciting studies with multiple agents combining BTK inhibitors in CLL and other malignancies.Certainly, in chronic lymphocytic leukemia, the novel doublets are very interesting, very effective. Acalabrutinib plus venetoclax has been approved in treatment of previously untreated CLL. Zanubrutinib is being investigated in combination with another BCL2 inhibitor, sonrotoclax, in CLL, in a frontline setting in a randomized study. I do believe we can anticipate high efficacy of that regimen as well, followed by hopefully regulatory approvals. There are also interesting studies employing pirtobrutinib. At this EHA, there is data which show high efficacy of pirtobrutinib, venetoclax, rituximab in relapsed CLL setting. So that is a regimen which I think some of us will start using more frequently in the future. So the doublets and triplets with BCL2 inhibitor CD20 antibodies is certainly where the field is moving, also them being time-limited therapies. And would be interested to see some data with bispecific antibody combinations. There are some studies in Germany which are combining BTK inhibitor pirtobrutinib with epcoritamab in Richter’s. So there is still a lot of work to be done with those. And, you know, in the field of CAR-T, CAR T-cell therapy still is, by itself, seems to be maybe a bit too toxic, maybe a bit less efficacy than we would like in chronic lymphocytic leukemia, specifically talking about liso-cel. But we did an analysis, retrospective analysis of real-world efficacy of liso-cel. And it seems higher than in the original study, actually. And I think that is in part because in many instances, liso-cel has been actually given together with pirtobrutinib or other BTK inhibitors. So there is clearly a combination effect there. So that needs to be studied as well, as I think that would be one way to improve efficacy of CAR T-cells in CLL. So a lot of exciting studies with multiple agents combining BTK inhibitors in CLL and other malignancies.

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