ICML 2023 | Evaluating radiotherapy bridging in patients with LBCL receiving CD19 CAR-T therapy

So we’re very good at real-world evidence from several thousands of patients with large B-cell lymphoma treated with CD 19 CAR-T. But our knowledge about optimal bridging for these patients is still quite limited. So bridging therapy being treatment you can give between leukapheresis and the actual CAR-T infusion, which might be systemic therapy, radiotherapy or a combination of both. So the potential advantage of using radiotherapy as bridging is that A, we know that radiotherapy is highly effective even in disease that is chemo-refractory with limited toxicity and largely non-overlapping toxicity to CAR-T. We also know that radiotherapy can control critical sites of disease that are more likely to become CAR-T refractory later on and more and more preclinical data to suggest that there is a priming and synergistic effect of radiotherapy with CAR-T. So despite these potential advantages for radiotherapy, bridging is not widely used and that’s partly due to the logistical challenges to plan and deliver radiotherapy within this very tight timeline in the CAR-T pathway, but also some uncertainty about patient selection because most of these patients heading to CAR-T will be advanced stage, high-risk patients. So until now we had quite limited data available to guide radiotherapy bridging, so small single center studies. And this was our aim to look into outcomes of radiotherapy bridged patients from a larger multicenter cohort. So we included 763 patients approved for third line standard of care CAR-T across 12 UK centers, and 90% of these patients received some form of bridging therapy, 24% radiotherapy containing bridging mostly single modality, but also a few combined modality treatments. And what we saw is that patients receiving radiotherapy as bridging had excellent outcomes, so low dropout rate and long progression-free and overall survival, which importantly was also seen in advanced stage disease. So somehow indicating that the potential benefit of radiotherapy might go beyond this classical indication of limited stage disease. And what was also interesting to see is that the use of radiotherapy bridging increased over time. So centers appear to be more and more confident to use this bridging modality for the CAR-T context. Obviously, we can’t directly compare different bridging modalities because of a significant selection bias. So if a patient has very fast progressing high-risk disease, we would tend to choose systemic therapy. But what we can say from these data is that radiotherapy bridged patients have excellent outcomes and we should be encouraged to extend the indication of radiotherapy bridging beyond limited stage disease. And hopefully these data will provide some baseline to develop specific radiotherapy bridging protocols and hopefully more pre-clinical data will be released to indicate how from an priming point of view, how the optimal sequence would be or in terms of fractionation, dose and timing prior to CAR-T, so we optimally harness this potential priming effect.