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Oxford Myeloma Workshop 2025 | The potential role of CELMoDs for overcoming IMiD resistance in patients with multiple myeloma
Sarah Gooding, MD, PhD, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK, comments on the potential role of cereblon E3 ligase modulators (CELMoDs) for overcoming resistance to immunomodulatory drugs (IMiDs), such as pomalidomide and lenalidomide, in patients with multiple myeloma (MM). Dr Gooding highlights that early data from trials of iberdomide and mezigdomide suggests these agents may be efficacious in a proportion of patients; however, work remains to be done to understand the underlying mechanisms and which patients will benefit. This interview took place at the 5th Oxford Myeloma Workshop in Oxford, UK.
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Transcript (AI-generated)
So, CELMoDs are going to be a very interesting and exciting class of drugs to work out how to use. The early data from iberdomide and mezigdomide trials shows that they do have the potential to overcome IMiD resistance in a reasonable proportion of patients. And it will take a lot more work to work out how and why that’s happening and which people it does happen in and which people it doesn’t happen in...
So, CELMoDs are going to be a very interesting and exciting class of drugs to work out how to use. The early data from iberdomide and mezigdomide trials shows that they do have the potential to overcome IMiD resistance in a reasonable proportion of patients. And it will take a lot more work to work out how and why that’s happening and which people it does happen in and which people it doesn’t happen in.
And it brings us into the really quite complicated landscape of IMiD resistance, because that involves genetic changes in the tumour, it involves phenotypic changes in the tumour, but also the immune microenvironment and, you know, the state of the T-cells, whether they can be affected by the CELMoD or the IMiD still, which really is potentially quite a big effect as well.
So I think there’s a lot of work still to be done. But the bottom line is that these are a class of drugs that will still work in patients who were resistant to pomalidomide and lenalidomide before. So that will be very exciting to work out and to see what we can combine them with. Can they be used to enhance the activity, for example, of immunotherapies like T-cell engagers? It’ll be great to watch that data come through in the next few years.
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