Using Radiotherapy Strategically Alongside CAR T, Bispecifics in Myeloma

CancerNetwork^® spoke with Alexandra Dreyfuss, MD, MS, an assistant professor in the Department of Radiation Oncology at the University of Miami Sylvester Comprehensive Cancer Center, about 2 presentations she gave at the 2026 American Society for Radiation Oncology (ASTRO) Annual Meeting, which related to the evolving role of radiotherapy in multiple myeloma.

In the first presentation, a lesion-level PET/CT analysis of 102 patients with relapsed/refractory multiple myeloma treated with ciltacabtagene autoleucel (Carvykti), 24-month progression-free survival (PFS) and overall survival (OS) rates were 48% (95% CI, 37%-61%) and 74% (95% CI, 64%-85%), respectively.¹ Extramedullary and paramedullary disease, present in 26% and 12% of patients before CAR T-cell therapy, increased to 47% and 25% of patients at progression, and both were independently associated with inferior PFS (HR, 7.1 and 20.4, respectively) and OS (HR, 3.9 and 5.4, respectively).¹ In the second presentation, an educational session on strategic radiotherapy integration in multiple myeloma, Dreyfuss discussed how radiotherapy might be sequenced around CAR T-cell therapy and bispecific antibodies as those agents become standard parts of the treatment course.²

Dreyfuss discussed how the role of radiation is expanding in multiple myeloma, how to weigh bridging vs consolidative radiotherapy strategies around CAR T-cell infusion, the current evidence for combining radiation with bispecific antibodies, the biggest gaps in prospective data, and when community radiation oncologists should loop in a multidisciplinary hematology-radiation discussion. She noted that patients with multiple myeloma are living longer on CAR T-cell therapy and bispecific antibodies, creating more opportunities to use modern, lower-toxicity radiotherapy strategically rather than purely for palliation, and that lesion-level data on where progression occurs could help identify which patients benefit most from earlier integration of radiation.

CancerNetwork: How is the role of radiation in multiple myeloma expanding as CAR T-cell therapy and bispecific antibodies become standard parts of the treatment sequence?

Dreyfuss: I think it’s expanding in several ways in relation to bispecifics, CAR T, and novel therapies in multiple myeloma in general. From the radiation oncology perspective, we are seeing that patients respond well, but they do eventually typically relapse. That means not only are patients living longer, but they may need more therapy, so there’s more time where radiation can come into play. It’s also made us more interested in seeing if we can use radiation earlier on, before relapse, in a strategic way to help either prolong the time patients get benefit from these therapies or prevent some of the relapses that are happening.

How do you see radiotherapy fitting in as a bridging strategy before infusion vs a consolidative strategy afterward for high-risk disease sites?

At this point, both are considered very viable options. I don’t know that we have data to suggest one is more effective than the other. In a preliminary way, the way I’d think about it is that for patients with certain higher-risk features, whether systemic or radiologic high-risk features, incorporating radiation earlier might make sense. Number one, we have a clearer target of what we’d want to treat with radiation, and number two, if a patient is higher risk, they probably need more therapy to get them to a place where they could respond better to CAR T.

Whereas for a patient with fewer risk factors prior to CAR T, it might make more sense to see how they do with CAR T first, and if they have an incomplete response, at least in the early setting, intervene with radiation then, potentially sparing some patients from needing any additional therapy. That’s how I’d think about it now. I don’t know that we can say one approach is better than the other at this point.

What's the current evidence base for combining radiotherapy with bispecific antibodies in multiple myeloma? How does timing differ from what's been learned in the CAR T setting?

A few centers have just started to look at radiation combined with bispecifics. There was initially a small study that combined [patients with multiple] myeloma and lymphoma because there were so few patients, and it reported basic safety signals. A larger study came out from the University of Pennsylvania within the past year or so, specifically in multiple myeloma, that looked at radiation combined with bispecifics and again reported basic safety and toxicity data showing it’s a feasible approach; there aren’t typically high-grade toxicities with the combination.³ That study also reported some efficacy outcomes suggesting that comprehensive radiation, meaning all sites of disease present on imaging, could potentially improve PFS.

I’ve been part of a similar effort at Memorial Sloan Kettering Cancer Center, where I did my residency, looking at bispecifics and radiation, and we’ve seen similar results in terms of feasibility and safety, and in terms of not needing to delay a patient’s bispecific treatment because of radiation therapy. We’ve expanded that into looking at what radiation approaches would best fit with the goal of combining with bispecifics, which might be a little different than how radiation is used in other settings in multiple myeloma.

To summarize, there are basic emerging clinical data on safety signals, but I don’t think we have great data yet on how best to combine radiation with bispecifics. Whether there are ways to be more strategic than simply palliating a site that’s causing a patient’s symptoms—that’s hopefully what we’ll be working on.

What do you see as the biggest gap in prospective data for radiotherapy integration in multiple myeloma, and what would you prioritize studying first?

There’s a general gap in prospective studies of radiation use in multiple myeloma. There have probably only been a handful of studies ever done on any question related to radiation in multiple myeloma. We have an ongoing study looking at a dose question for radiation in myeloma, and dose has always been a big question in myeloma; there’s a huge range of doses used, from some of the lowest doses we use for any cancer to some of the highest doses we use for very radioresistant cancers.

But looking toward the future, I’d say I would probably start with prospective studies in either the CAR T or bispecific space because those therapies are becoming increasingly common and have had very good response rates. Some of the ideas for those studies are alluded to in some of my presentations at ASTRO, whether that’s using radiation in the pre-CAR T bridging setting or the early post-CAR T setting.¹ I’m not presenting on this specifically, but in relation to bispecifics, using radiation to target what we think are higher-risk sites for failure is another aspect. I think there’s an opportunity in those 2 populations to translate what we’re seeing on a retrospective basis into prospective work.

How should community radiation oncologists who see multiple myeloma less often than academic centers think about when to loop in a multidisciplinary hematology-radiation discussion vs treating more reflexively for palliation?

I’d say you can think about it in 2 ways. For any patient who is particularly high risk, whether molecularly or radiologically, or who has received multiple therapies they’ve been refractory to and progressed on quickly, that’s a patient who deserves a little more thought from the radiation perspective. Those patients probably need more therapy than whatever is typically offered. That’s one population where I’d suggest looping in a multidisciplinary discussion.

Then, on the opposite end, patients who have fairly well-controlled and managed disease, but maybe have something come up here or there [like] a suspicious site on imaging, could also potentially be referred to more multidisciplinary management, where imaging can help guide the use of radiation in combination with systemic therapy.

References

1. Dreyfuss A, Yahalom J, Nemorovsky D, et al. Patterns of progression after BCMA CAR T-cell therapy in relapsed/refractory multiple myeloma: a lesion-level PET/CT analysis. Presented at: 2026 ASTRO Annual Meeting; September 26-30, 2026; Boston, MA. Abstract 207.
2. Dreyfuss A. Strategic integration of RT in multiple myeloma. Presented at: 2026 ASTRO Annual Meeting; September 26-30, 2026; Boston, MA.
3. Patel H, Hubbeling H, Yu K, et al. Outcomes of radiation integrated with T-cell-engaging bispecific antibodies in relapsed/refractory multiple myeloma. Blood Adv. 2026;10(4):1395-1399. doi:10.1182/bloodadvances.2025017939