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iwCLL 2025 | The potential role of BCL2 inhibitors in the CLL treatment landscape
Jacob Soumerai, MD, Massachusetts General Hospital, Boston, MA, provides insight into the potential role of the BCL2 inhibitors venetoclax, sonrotoclax, and lisaftoclax in the treatment landscape for chronic lymphocytic leukemia (CLL). Dr Soumerai highlights that data from ongoing clinical trials, such as the VENETIAN (NCT06428019) and GLORA (NCT06104566) trials, will inform how these agents are integrated into the current treatment paradigm. This interview took place at the biennial International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2025 in Krakow, Poland.
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Transcript
I think that all of these BCL2 inhibitors have potential to fit into the future landscape of therapies in CLL. For one, venetoclax is a terrific agent, and in particular, if they’re able to develop a more simplified TLS mitigation approach with the VENETIAN study that can be used in the community. This is a drug with a very established track record over many years and has much greater potential to improve patient outcomes if it can be delivered to more patients...
I think that all of these BCL2 inhibitors have potential to fit into the future landscape of therapies in CLL. For one, venetoclax is a terrific agent, and in particular, if they’re able to develop a more simplified TLS mitigation approach with the VENETIAN study that can be used in the community. This is a drug with a very established track record over many years and has much greater potential to improve patient outcomes if it can be delivered to more patients.
Sonrotoclax is, you know, we await data from the randomized phase three trial in which sonrotoclax and zanubrutinib is being compared against venetoclax and obinutuzumab. This is a very important study. It’s got a primary progression-free survival endpoint, and certainly if this proves to be more effective than the current standard of venetoclax and obinutuzumab, this would have a major impact and likely be used quite a bit in the future for patients who require initial therapy for their CLL. Of course, we’re eager to see if the relatively low rates of GI toxicities in the phase 1-2 study, which were generally grade 1, if this, again, translates into favorable safety outcomes in the phase three data, this could have an impact. But I think that the most important question here is what the final ramp-up strategy and TLS laboratory requirements will look like. Given that for years we’ve had venetoclax-based therapies that are not being used despite terrific activity, in unfortunately not enough patients. I think that what the ramp-up strategy will look like is going to be really key to determining its uptake in the community and really throughout the CLL community.
Lisaftoclax has really a distinct development program. It’s being explored as this add-on strategy. And so if the phase three GLORA trial is successful, this would tell us that the addition of lisaftoclax to patients with inferior long-term responses on acalabrutinib might benefit from the addition of lisaftoclax. How this would fit into the current treatment landscape and what this means for its future development, I think, has some additional questions. But clearly, this is a very important agent in this disease as well with significant potential.
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