Bridging Radiation and CAR T-cell Therapy May Have Benefit in Relapsed/Refractory DLBCL

Timothy Robinson, MD, PhD, spoke with CancerNetwork^® during the 2024 American Society for Radiation Oncology (ASTRO) Annual Meeting about the potential clinical utility of combining bridging radiotherapy with CAR T-cell therapy for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). At ASTRO, he gave a presentation focusing on the rationale for combining these treatment modalities in this patient population.

Robinson, an assistant professor of therapeutic radiology at Yale Cancer Center, described how the addition of bridging radiotherapy may especially benefit patients with a single site of disease, detailing the factors of the tumor microenvironment that may limit the efficacy of CAR T-cell therapy when administered by itself. He spoke about his prior experience at Moffitt Cancer Center to illustrate how a protracted course of radiation before giving CAR T-cell therapy may improve outcomes for patients. Additionally, he acknowledged that the addition of radiation may not be suitable when a patient has several sites of disease.

Transcript:

There are absolutely patients [who] we think they would benefit from radiation in addition to CAR T. The nice thing about CAR T is that it goes all over the body. The place where it struggles is when you have a large tumor, for many reasons. One [reason is] the sheer tumor burden. T cells can only amplify so much before they just get worn out, give up, and get outnumbered [due to the] total burden.

[Additionally], we know that these very large tumors—this is an area of research; we haven’t shown this, but it’s possible—there could be things that are very inhospitable in that microenvironment. There could be areas of hypoxia and acidosis that these T cells just cannot deal with. We also know that, sometimes, [when] we have a large tumor, just the pressure of a solid tumor results in interstitial pressure, where it’s like a balloon or a tire that’s been blown up to full, and it’s just stiff and hard to physically get things into it, like T cells.

[Therefore,] there are a lot of reasons why a big, angry, single tumor is the most difficult thing for CAR T to address, whereas [with] radiation, that’s where we shine. For patients, in terms of bridging, if you have 1 site of disease that is large, bulky, high-risk, and hypoxic, that’s where radiation can have the most value for bridging. In my Moffitt Cancer Center days working with those folks, we had a paradigm shift, even in the early days, where [the idea was to] get in the CAR T as quickly as possible. But we shifted practice so that if you had somebody with a single site of disease, we would delay CAR T so that we could do a more protracted course of radiation to "cure" what we could see, and then have the CAR T come in afterward.

Localized disease up-front is definitely a place where radiation benefits. On the flip side, [it’s the] same thing. If you [have received prior] CAR T and have one site of the disease that’s not responding, that’s a great place for radiation. Where it’s not a great place for radiation is if you have 50 sites of disease, and they’re all small throughout [the body]. That is a very diffuse process that we’re not going to be able to help with in a focal way.

Reference

Robinson T. Radiotherapy’s effective incorporation with chimeric antigen receptor (CAR)-T cell therapy for relapsed/refractory diffuse large B-cell lymphoma. Presented at: 2024 American Society for Radiation Oncology Annual Meeting; September 29-October 2, 2024; Washington, DC.