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EHA 2026 | The promise and impending approval of CELMoDs for multiple myeloma
Fredrik Schjesvold, MD, PhD, Oslo University Hospital, Oslo, Norway, discusses the promise and impending approval of cereblon E3 ligase modulators (CELMoDs) for the treatment of relapsed/refractory (R/R) multiple myeloma (MM), highlighting key trials that will support regulatory decisions. Dr Schjesvold notes that the results of the SUCCESSOR-2 trial (NCT05552976) are particularly exciting, showing a doubling of progression-free survival (PFS) with mezigdomide, carfilzomib, and dexamethasone (MeziKd) versus Kd in a heavily pretreated population. This interview took place at the 31st Congress of the European Hematology Association (EHA) in Stockholm, Sweden.
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Transcript
I think this talk you’re referring to is a talk that’s mostly based on the CELMoDs, the upcoming data on the CELMoDs. I think it’s an exciting year for the CELMoDs. We have had lenalidomide and pomalidomide the IMiDs, for many years, but now we have more efficacious products with iberdomide and mezigdomide and they’re getting closer to approval and we’re going through those data...
I think this talk you’re referring to is a talk that’s mostly based on the CELMoDs, the upcoming data on the CELMoDs. I think it’s an exciting year for the CELMoDs. We have had lenalidomide and pomalidomide the IMiDs, for many years, but now we have more efficacious products with iberdomide and mezigdomide and they’re getting closer to approval and we’re going through those data. What we know about iberdomide is still a bit less than for mezigdomide. We know that the EXCALIBER trial which is the second line relapse trial, where you compare iber-dara-dex versus dara-bortezomib-dex, we know that the MRD results, which are what the approval is going to be based on, are positive, but we will not see the data until this autumn in Glasgow. At the same time, there is an iberdomide maintenance trial ongoing versus lenalidomide after transplant with a chosen dose of 0.75. The running data looks really good but now we have to wait some time for those results.
More exciting today is mezigdomide where the SUCCESSOR-2 trial just at ASCO a couple of weeks ago showed doubling of PFS over carfilzomib-dex in patients that are all dara-exposed, so a quite heavily pretreated population. Those data with a PFS of 18 months is similar to the cilta-cel study with CARTITUDE-4 in the same population of patients that are exposed. And it’s an immunotherapy-free regimen. So it means that you can use it before. It doesn’t hamper the later immunotherapy. You can use it after. It’s a tablet, so it’s very sort of, if approved, available in every possible center that treats with carfilzomib, but everybody does that. So I think it’s a regimen with many possibilities. And now it will be approved in the US, and a little bit later probably in Europe, and become the first CELMoD to be approved and efficacious in a randomized trial in this population. There is even another CELMoD coming, it’s selinexor, which is still in early phase trials, but looking very efficacious. It’s the first CELMoD or drug that’s not coming from Celgene or BMS. So it’s exciting to see that they also get a competitor.
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