Oxford Myeloma Workshop 2025 | Challenging the current paradigm of sequencing in multiple myeloma

In myeloma, we used to have three big drug classes: proteasome inhibitors, immunomodulatory drugs, and then CD38 antibodies. We now have new targets, and they can be targeted by new therapies. So philosophically, we were thinking about, well, we’ll start with an immunomodulatory drug plus a proteasome inhibitor, and then go to a second-generation proteasome inhibitor and an immunomodulatory drug and we did have clinical benefits. They’re all licensed. But the key challenge to this paradigm is because we now have trials showing that if you move from patients who have been exposed to proteasome inhibitors and immunomodulatory drugs to, say, a BCMA-targeted therapy, patients are clearly getting a significant benefit in some of the trials that have come through. So this is starting to challenge the paradigm of moving from first-generation to second-generation immunomodulatory drug and proteasome-based combination to completely changing drug class. We need further data. There may be patients who may be more beneficial by switching classes. There may be patients we feel that who could benefit from a second-generation approach. But in time with further data I think we’ll be clearer about whether switching class or maintaining the same drug class is beneficial and if so for which sort of patients.

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