Abstract:

Chimeric antigen receptor (CAR) T cell therapy has emerged as a completely new method of targeting relapsed/refractory B cell malignancies with impressive results leading to FDA approval. Nonetheless, a subset of patients will not respond to CAR T cell therapy, as evidenced by refractory disease on imaging 4-6 weeks after CAR T infusion. While radiation therapy is already being studied in the ‘bridging’ setting at other institutions, we hypothesize that RT at the time of early refractory disease may enhance CAR T cell therapy by providing local control in a context in which patients typically have no remaining systemic therapy options. Furthermore, it has also been shown that RT has the potential to improve immunologic response against cancer cells, by increasing tumor associated antigen repertoire and providing an antigen-independent mechanism of tumor cells resistant to CAR T cell. We will review the background of CAR T in relapsed/refractory lymphoma and highlight the importance of my pilot clinical trial involving CAR T cell therapy lymphoma patients who have refractory disease in short-term follow-up after CAR T cell therapy infusion to investigate A) Feasibility, safety, toxicity, and efficacy of RT in the early refractory setting in CAR T cell therapy B) Biomarkers of RT response, such as CAR T infiltration into tumor, and pathway changes induced by RT which may enhance CAR T cell therapy.  

Short bio: