Where Do CELMoDs Fit With CAR T Cells and Bispecifics in Multiple Myeloma?

As CAR T-cell therapy and bispecific antibodies expand in multiple myeloma, CELMoDs such as iberdomide (Zenbexus) are being explored as a bridging therapy before CAR T-cell therapy, a maintenance option afterward, and a way to help reverse T-cell exhaustion between immunotherapies.

Surbhi Sidana, MD, associate professor of medicine at Stanford University, where she leads the myeloma cellular immunotherapy program and chairs the American Society of Hematology (ASH) Committee on Communications, spoke with CancerNetwork^® about where she sees CELMoDs fitting relative to other T-cell–redirecting therapies. She spoke in the context of the FDA granting accelerated approval to iberdomide in combination with daratumumab and hyaluronidase-fihj (Darzalex Faspro) and dexamethasone for patients with relapsed/refractory multiple myeloma.

Transcript:

CancerNetwork: Given your own focus on CAR T-cell therapy and bispecifics, where do you see CELMoDs fitting relative to T-cell–redirecting therapies? Do you see it as a bridge, a post-relapse option, a combination partner to boost immune effects, or fulfilling another role?

Sidana: Where do we see the role of this in academic centers, in a practice like mine, where we’re giving CAR T and bispecifics that have very high MRD-negative rates? It’s a complement. It’s available in the community for patients who can’t travel or come here, but for [patients who receive] CAR T, if I do CAR T as their first relapse, they need bridging; they can get this as bridging therapy for the 2 or 3 months while we want them to get a response.

Then, in some patients where we want to give maintenance [therapy], and we’re studying that in clinical trials, it’s becoming more commonplace. If they’re still MRD positive after CAR T, we know these patients don’t do well; if they’re functionally high risk or have extramedullary disease [EMD], we know they won’t get years and years [of benefit]. We want to give them some easy maintenance that doesn’t require coming back for injections or infusions. [CELMoDs] can play a very complementary role.

Then, post-relapse, it’s a great option. Just a couple of days ago, I had a patient who was relapsing and had everything under the sun. Before this approval, that would have been a very difficult conversation; they’d had all CAR T and bispecifics and weren’t eligible for a trial. I said, “Guess what, we have a new drug you might be eligible for that’s oral.” This is [also] an older patient, so this brings hope as a relapse option as well.

While patients get a lot of durable disease control, many still relapse. [It is a] relapse option, maintenance option, and bridging option. As we sequence these immunotherapies between bispecifics and CAR T, if someone got a bispecific first, we have concerns about T-cell exhaustion. We know these CELMoDs can reverse T-cell exhaustion to a level, so we can perhaps put someone on one of these CELMoDs, iberdomide right now, give them 2 or 3 months of it, get myeloma control, and then manufacture for CAR T. Those clinical trials are also ongoing. Even in academic practice, where we’re using CAR T and bispecifics, CELMoDs have a huge role to play. Of course, they’re also being tested in combination with bispecifics.

Reference

FDA grants accelerated approval to iberdomide with daratumumab and hyaluronidase-fihj and dexamethasone for multiple myeloma. News release. FDA. August 13, 2026. Accessed August 24, 2026. https://tinyurl.com/38258auk