ASH 2025 | Bispecific antibodies in myeloma: top trial updates from ASH 2025

So at this year’s ASH 2025 meeting in Orlando, there’s been really many exciting abstracts being presented related to multiple myeloma. I think one of the really exciting themes that have emerged is the earlier incorporation of bispecific T-cell antibodies in the treatment paradigm for multiple myeloma. So over the last three to five years, we’ve seen an era of the T-cell redirecting agents, including CAR-T therapies and bispecific T-cell antibodies, incorporated in late-line and even earlier-line myeloma with CAR-T therapy specifically. And in the case of bispecific T-cell antibodies, really they have shown unprecedented activity for an off-the-shelf agent and heavily pre-treated relapsed/refractory multiple myeloma in patients with at least four prior lines of therapy, which is currently the current regulatory approval in the United States. And so the next step is, how do these agents potentially perform in earlier relapsed/refractory multiple myeloma and potentially newly diagnosed myeloma? And there have been several abstracts addressing this exact question at this year’s ASH meeting. 

So one of the most exciting abstracts being presented that’s being talked about a lot is a late-breaking abstract that will be presented later at the meeting, the MAJESTEC-3 trial, which basically compared the regimen of teclistamab and daratumumab versus standard of care triplets with daratumumab, bortezomib and dexamethasone or daratumumab, pomalidomide and dexamethasone in patients with one to three lines of prior therapy. And the regimen of teclistamab and daratumumab showed not only improvement of progression-free survival, but overall survival compared to the standard care triplets. So clearly, there’s clear efficacy of the use of bispecific antibodies in combination with daratumumab in earlier relapsed/refractory multiple myeloma. 

And then we also have data in newly diagnosed patients as well. And so there’s a couple abstracts in particular that looked at using bispecific antibodies either as part of induction or consolidation. One notable abstract is the IFM2021-01 arm A abstract, which looked at the combination of teclistamab and daratumumab in transplant ineligible newly diagnosed myeloma patients, really showing unprecedented 100% MRD negative rates at 10 to the minus 6 in MRD-evaluable patients, which is really unprecedented in this particular patient population. 

And then we also saw a really interesting abstract using bispecific antibodies as part of consolidation. So the immuno-plant study was being performed at the University of Miami, and essentially patients received standard induction therapy, three or four drug induction therapy. If they were MRD positive, then received linvoseltamab, which is a BCMA bispecific antibody, for four to six cycles as part of consolidation. Again, 100% MRD negative rates at 10 to the minus six. So I think all these abstracts have really shifted the focus of the use of these agents in earlier lines of therapy and in newly diagnosed myeloma. And I firmly believe this will be the future of the use of these agents in the years to come.

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