For patients with relapsed/refractory multiple myeloma, recent therapeutic advances—including the continued development of bispecific and trispecific antibodies—are poised to reshape the treatment landscape and offer renewed clinical momentum, according to Joshua Richter, MD.
“I think [trispecific antibodies] are going to be part of the future of the management of myeloma,” Richter said. “We’re excited about these and other assets that are coming along. The question is: Can we get somebody the perfect balance of efficacy and toxicity—but with 1 drug?”
In an interview with OncLive®, Richter discussed the evolving treatment paradigm in 2025, including the FDA approval of linvoseltamab-gcpt (Lynozyfic) and the anticipated decision on belantamab mafodotin (Blenrep)–based combination regimens. He highlighted how novel modalities such as CAR T-cell therapies and trispecific antibodies targeting BCMA and GPRC5D are enabling deeper and more durable remissions. Richter also reflected on recent regulatory developments and emphasized the importance of practical, accessible therapies for patients who may not be candidates for advanced cellular treatments.
Richter is an associate professor of medicine at the Tisch Cancer Institute and director of Myeloma at the Blavatnik Family – Chelsea Medical Center at Mount Sinai in New York, New York.
OncLive: What is the current state of the treatment landscape for relapsed/refractory multiple myeloma in 2025?
Richter: 2025 has become an exciting time for the world of relapsed and refractory multiple myeloma. We’ve had several recent approvals, including the approval of linvoseltamab, the BCMA×CD3 bispecific antibody. We have a Prescription Drug User Fee Act date of October 23 for the potential approval of belantamab mafodotin[–based regimens], the BCMA-targeted antibody-drug conjugate, either in combination with bortezomib (Velcade) or pomalidomide (Pomalyst) [and dexamethasone] in early relapsed myeloma.
We’re really trying to figure out in the relapsed/refractory world not, ‘Can we cure the disease?’ All the frontline trials are seeking to do that, [and we’re asking], ‘The disease has come back; can we push it so far down in remission that it really doesn’t come back within the patient’s lifetime?’
There are a lot of great trials that are seeking to do this, either with CAR T-cell therapy—and we have a whole bunch of new CAR T-cell therapies in the relapsed world—targeting things like BCMA, GPRC5D, and some [other agents] are dual-targeted, such as BCMA and CD19, where we’re trying to not just kill the myeloma cell but also the myeloma stem cell.
What has driven the recent momentum with bispecific and trispecific antibody development within this space?
[There are] a bunch of trispecific antibodies now in the relapsed/refractory world—with the Janssen BCMA×GPRC5D×CD3 trispecific [JNJ-79635322] and [ISB 2001] recently acquired by AbbVie, which is a BCMA×CD38×CD3 trispecific. Over the next couple of years, we [may increase] from 2 or 3 [agents], and we’re leveling up in the world of relapsed and refractory myeloma.
Trispecific data [for JNJ-79635322 presented] at the 2025 EHA Congress showed a 100% response rate at the [recommended phase 2 dose]. The sky’s the limit. We’re excited about what the future holds in this landscape.
In light of the recent Oncologic Drugs Advisory Committee (ODAC) vote regarding belantamab mafodotin, what were your key takeaways from the discussion, and how do you see the advisory committee’s stance influencing access to therapies in the relapsed/refractory myeloma space moving forward?
One of the things that the ODAC really brings to light in my mind is some of the competing interests that we have to think about. As a clinician, my sole focus is the patient in front of me, but I recognize that the government is trying to balance everything here because they need to evaluate what the impact is going to be on a much broader scale.
My hope is that the patient advocate voice that was heard very loudly during the ODAC [meeting] will resonate, and my hope is that the drug will still be approved. My guess is that they will take a tack that they’ve used in previous approvals in myeloma—when the ODAC voted negatively—by approving the drug but with black box warnings.
There are a lot of places in the United States where CAR T-cell therapy are not available, and even bispecifics may not be feasible. The reality is, a drug like [belantamab mafodotin] could be given anywhere. I’m hoping that we have this agent in our tool shed. It’s not for everybody, but there are quite a number of people out there who would benefit from having belantamab [mafodotin].
What excites you most about the clinical potential of trispecific antibodies in relapsed/refractory myeloma?
One of the things that we’ve learned across the last few years is the importance of 2 main targets: BCMA and GPRC5D. We’ve seen this with a number of CAR T-cell therapies and bispecific antibodies. With the phase 1/2 RedirecTT-1 trial [NCT04586426], we saw that when we combined these two targets by giving both talquetamab-tgvs [Talvey] and teclistamab-cqyv [Tecvayli], we saw unprecedented response rates, especially in some of the harder-to-treat [patients with] extramedullary disease.
The question is: Can we achieve the same type of efficacy, but with one drug instead of multiple drugs, in an effort to maintain those response rates but reduce the adverse effects? That’s one of the things that the trispecifics are trying to do. So far, we’re starting to get a hint that these are highly efficacious drugs.