On Route to Chimeric Antigen Receptor T-cell (CAR T) Therapy, Less Is More: Adaptive Bridging Radiotherapy in Large B-cell Lymphoma

Abstract

CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has appreciably advanced treatment for relapsed or refractory large B-cell lymphoma (LBCL). During the critical interim of four to six weeks, until CAR T-cells are ready, radiation therapy (RT) can be used to control the disease. We present the case of a 64-year-old female with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who received adaptive RT for bilateral adrenal masses as a bridging strategy before undergoing CAR T-cell therapy and enrolled in an adaptive RT clinical trial. A plan was developed to deliver up to five once-weekly fractions (5 Gy per fraction) of CT-based online adaptive RT (Varian Ethos with HyperSight imaging, Varian Medical Systems, Palo Alto, CA). The patient experienced rapid symptomatic relief, with no RT-related toxicities. The patient received RT at only half of the sessions (two out of four sessions) due to excellent tumor shrinkage on cone-beam CT (CBCT). As such, the patient was treated at a lower total dose (10 Gy) than she otherwise would have received with standard RT. Post-RT PET/CT showed significant disease regression, compatible with partial response, prior to CAR T-cell infusion. This case shows the successful application of adaptive RT as bridging therapy prior to CAR T-cell therapy, and we expect the results of this adaptive RT trial to guide the future of adaptive RT in relapsed/refractory B-cell lymphomas.