IMS 2026 | Emerging combination strategies at first relapse in multiple myeloma

The treatment of myeloma at first relapse is rapidly changing due to the advent of T-cell directed immunotherapies. What I’ve been discussing is how the treatment paradigm is going to shift now that we have data with combination therapies of bispecific antibodies and indeed with the new cell mods. So what we’ve seen so far is data with teclistamab, either as monotherapy in the MajesTEC-9 study or in combination with daratumumab in the MajesTEC-3 study. Both clinical trials show significant improvements in progression-free survival and overall survival compared to the standard of care control arms. What we also see in the MajesTEC-3 study is really an unprecedented PFS and potentially a plateau emerging at about six months. We also find that for high-risk patients that they are also maintaining a very high level of progression-free survival, superior to anything that we’ve seen before, which is very encouraging. We also have data with talquetamab in combination with daratumumab and pomalidomide, all just with daratumumab. But the effect of the pomalidomide doesn’t seem to be so great, although it does induce higher rates of grade three or four neutropenia. Now, moving away from the bispecific antibodies, we have mezigdomide, which is a new cell mod. And in the SUCCESSOR-2 clinical trial, there was a significant improvement in progression pre-survival of MeziKd as compared to Kd. We haven’t yet seen a survival benefit, but the follow-up time is quite short. So where do I think this is going to be in the future? Well, certainly I think some of the conventional treatments that we’ve been using, our second line will now disappear and we’ll move predominantly to a BCMA-directed therapy moving forward, whether that’s with the belantamab combinations, Siltacel combinations which are already in existence, or now with teclistamab monotherapy, teclistamab and daratumumab. I think that the GPRC5D combinations can then follow after that. Due to the GPRC5D targets, there are some on-target off-tumor side effects, which can cause some problems with patients. So we tend to recommend the BCMA ahead of that. And certainly, mezigdomide and carfilzomib is a very good treatment for patients who might be a little bit frailer or for a patient who’s failing an immune therapy. Finally, if we think about patients with high-risk disease or extramedullary disease, I’m particularly interested in the MonumenTAL-6 trial, which is not yet fully published, but the press release suggests a hazard ratio of 0.11, showing a substantial improvement in PFS and overall survival compared to standard therapy. And we know that this is very effective for patients with extramedullary disease.

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