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ASCO 2026 | How the toxicity profile of golcadomide varies from that of lenalidomide
Marc Hoffmann, MD, University of Kansas Medical Center, Kansas City, KS, discusses how the toxicity profile of golcadomide, a cereblon E3 ligase modulator (CELMoD), differs from that of lenalidomide. Although golcadomide results in a significant risk of neutropenia, there is a lack of some of the toxicities associated with lenalidomide, including gastrointestinal (GI) toxicities, rash, and fatigue. This interview took place during the 2026 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.
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Transcript
So, with this particular compound, it is distinctly different from prior drugs that folks may have experience with, such as lenalidomide. So, it results in much deeper protein degradation, and I think most importantly, it binds at a different site, and so we do see a different toxicity profile compared to lenalidomide. We see the same on-target effects, so the proteins getting degraded, which are Ikaros and Aiolos, they directly cause cytopenias and in particular neutropenia...
So, with this particular compound, it is distinctly different from prior drugs that folks may have experience with, such as lenalidomide. So, it results in much deeper protein degradation, and I think most importantly, it binds at a different site, and so we do see a different toxicity profile compared to lenalidomide. We see the same on-target effects, so the proteins getting degraded, which are Ikaros and Aiolos, they directly cause cytopenias and in particular neutropenia. So we do significantly see neutropenia in the study. That did not compromise delivery of the chemoinmunotherapy backbone and did not result in any other significant challenges. But Golcadomide was free of a lot of the other really irritating toxicities of lenalidomide, GI toxicities, rash, some of the fatigue that can be associated with lenalidomide. So it’s a much easier drug to deliver and retains a lot of the benefits and in fact capitalizes on the overall mechanism of action and leads to significantly improved results without having some of the irritating toxicities of lenalidomide.
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