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SOHO Italy 2025 | What lies ahead for bispecifics in multiple myeloma?
Joshua Richter, MD, Mount Sinai Medical Center, New York City, NY, comments on the future of bispecific antibody treatment in multiple myeloma (MM), highlighting the potential for combination therapies and the exploration of fixed-duration therapy. Dr Richter also mentions the possibility of targeting FCRH5 with cevostamab, as an increasing number of patients will likely become refractory to BCMA and GPRC5D with the currently used therapeutic approaches. This interview took place at the SOHO Italy Annual Conference 2025 in Rome, Italy.
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Transcript
The first thing to look out for in myeloma is, you know, the natural progression of all therapies in myeloma is what I like to call looking for the dance partner. So we don’t like to give monotherapy, we like to give drugs with other drugs.
So I think the next big thing for bispecifics is going to be combinations...
The first thing to look out for in myeloma is, you know, the natural progression of all therapies in myeloma is what I like to call looking for the dance partner. So we don’t like to give monotherapy, we like to give drugs with other drugs.
So I think the next big thing for bispecifics is going to be combinations. So bispecifics with IMiDs like pomalidomide and lenalidomide and in the future, CELMoDs, combinations with daratumumab, talquetamab and dara, combinations even with selinexor or cyclophosphamide, or maybe even checkpoint inhibitors or gamma secretase inhibitors. And some data that we recently saw published from the RedirecTT-1 study about giving two bispecifics at the same time, giving teclistamab and talquetamab.
So I think the first big thing is going to be going beyond monotherapy with bispecifics. For example, the IMiDs, remember, you can give full dose IMiDs to kill plasma cells, but remembering that they’re immune modulators and they modulate NK T-cell activity, you can give lower doses not designed to kill plasma cells, but to boost the T-cell response. And we’ve seen some amazing data from the MonumenTAL-2 study presented by Jeff Matous about talquetamab and pomalidomide. And we typically get this in the clinic with two milligrams, not the four milligrams that’s normally given.
The other is additional targets. And to me, cevostamab, the FCRH5 bispecific, is really going to be a potent agent in the coming years because just as patients are now triple class refractory, refractory to Dara, an IMiD, and a proteasome inhibitor, we’re now engendering patients to be refractory to both BCMA and GPRC5D. So having FCRH5 as the next place to go is going to be an amazing way to go.
The other is now looking at who can we stop the bispecifics. Instead of keeping people on forever, we’re trying to figure out algorithms of who has the type of disease that we can give fixed duration so we can get patients off long-term therapy.
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