COMy 2022 | Recent updates on CELMoDs in multiple myeloma
Sagar Lonial, MD, FACP, Winship Cancer Institute of Emory University, Atlanta, GA, shares some recent updates on cereblon E3 ligase modulators (CELMoDs) for multiple myeloma and how these novel agents are transforming the treatment landscape. Prof. Lonial first reports on some data on the use of iberdomide plus dexamethasone in patients with triple-class refractory disease. Following this, Prof. Lonial discusses the encouraging activity observed in various CELMoDs and compares this to the use of immunomodulatory imide drugs (IMiDs). To conclude, Prof. Lonial discusses the activity and safety profile of CC-92480 and the impact that CELMoDs will have on the myeloma treatment landscape. This interview took place at the 8th World Congress on Controversies in Multiple Myeloma (COMy) 2022, held in Paris, France.
Transcript (edited for clarity)
So CELMoDs are the newest class of drugs that bind cereblon that are the grandson and the great grandson if you will, of thalidomide, lenalidomide and pomalidomide. And what I reported on here, was data that we’ve described before looking at iberdomide or CC-220 in combination with dexamethasone, showing about a 25% response rate in a large class, our large group of triple-class refractory myeloma, about 107 patients that I reported on at ASH...
So CELMoDs are the newest class of drugs that bind cereblon that are the grandson and the great grandson if you will, of thalidomide, lenalidomide and pomalidomide. And what I reported on here, was data that we’ve described before looking at iberdomide or CC-220 in combination with dexamethasone, showing about a 25% response rate in a large class, our large group of triple-class refractory myeloma, about 107 patients that I reported on at ASH. And then another cohort that looked at post-BCMA treatment and saw a similar 25% response rate with iber plus dex in that group as well. I think what we’re really encouraged about is activity of another drug in this class. What I think separates the CELMoDs from the IMiDs is that they are more potent in immune activation than we saw with len or pom. And we know that’s a major mechanism of their action, but really sets them up to be great partners with immune therapies like bispecifics, antibodies or even CAR-T cells.
The other data set that we looked at was the 92480, which is another CELMoD more potent perhaps even than iberdomide, slightly different adverse event profile, probably a little bit more on the heme toxicity. But what we know about both 480 and iberdomide is that their non-heme toxicity is much less significant than what we saw with len or with pom, making it easier to take them for a longer period of time. And so, what we saw with 480 was very high response rates in combination with dex, 40 to 50% in the recommended Phase II doses and similar to iberdomide, great partnership with bortezomib. And what we know about iber again, is great partnership with dara and carfilzomib as well.
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