ICML 2025 | The efficacy & toxicity of radiation therapy prior to CAR T-cell therapy in R/R myeloma

So CAR T-cell therapy is very promising for multiple myeloma. We know it’s a very effective strategy. We’re using it now regularly in relapsed refractory disease at UC San Diego, where I am now. And we also know that radiation is a very fast-acting, effective local approach to treating myeloma. So radiation has emerged as an effective bridging strategy and very promising bridging strategy for patients to either temporarily bridge them, you know, get them through that process. Sometimes it can take time to get your CAR-T ready. So we can use radiation to bridge that time. We can use it to palliate patients who may have painful lesions. And we also can use it to cytoreduce patients, which we know is associated with better outcomes after CAR-T. So with all this in mind, we looked at all of the patients at UC San Diego treated with BCMA-directed CAR T-cell therapy with a commercial product over the recent years. And we saw 51 patients. About half of them had received radiation. Half of them had systemic therapy alone. We wanted to see really what the efficacy and toxicity differences were between these approaches of using radiation versus not. We did not see any differences in outcomes. There is similar progression-free survival, similar toxicity profile, so both seem safe. We then looked at the differences between the timing of radiation. So did patients get radiation greater than a year before they got CAR-T, within a year of getting CAR-T, or really after apheresis and before CAR-T infusion? And similarly, we did not see any differences in outcomes based on the timing of radiation. And similarly, no differences in toxicity. I think one of the more interesting findings, besides just showing, again, adding to the literature that this can be safe and effective to do for bridging, I think that we looked at our patterns of failure. And interestingly, we saw higher rates of extramedullary disease being involved in the failures. And so that really calls into question, does CAR-T or do we have a hard time getting this immune cell infiltration into extramedullary masses? And so I think that we need more patients, we need more data to really see how we can address this. But I do think radiation could be a promising option. And I’m excited that there are several groups working on this question. I mean, the group at Penn has published, Mass General, and then my good friend and colleague, Dr Alexi Dreyfuss at Sloan Kettering, she really has focused on this work. So I’m excited that this is an opportunity for us all to contribute to the literature. And hopefully it’d be great if we can collaborate in the future to get these numbers together to answer some of these questions with small relapse rates.

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