Bridging Radiation Therapy Prior to Commercial Chimeric Antigen Receptor T-Cell Therapy for relapsed/refractory aggressive B-cell lymphoma

Abstract: Purpose CD19-targeting chimeric antigen receptor T-cell (CART) therapy has emerged as a promising treatment for relapsed/refractory aggressive B-cell lymphoma (r/rABL), culminating in two FDA-approved therapies, tisagenlecleucel (tisa-cel) and axicabtagene ciloleucel (axi-cel). Following leukapheresis and in preparation for CART infusion, contemporary bridging and lymphodepletion regimens rely mostly on cytotoxic chemotherapy. Here, in a cohort of patients treated with commercial tisa-cel and axi-cel, we show that bridging radiation therapy (bridging-RT) may offer a supplemental approach. Methods and Materials Thirty-one patients receiving commercial tisa-cel (n=13) or axi-cel (n=18) between August 2018 and February 2019 for r/rABL were retrospectively reviewed. Patients were divided into two groups: a) bridging-RT within 30 days (d) of CART infusion or b) non-bridging-RT (NBRT), where patients received either remote RT greater than 30d before CART infusion or no prior RT. Results Five patients received bridging-RT within 30d of CART infusion. Median bridging-RT dose was 37.5 Gy and completed a median of 13d prior to infusion. No grade 3 (G3) or higher RT-toxicities occurred. No patients in the bridging-RT group experienced G3 or higher CART-related toxicities (CRS or neurotoxicity), while 23% (n=6) and 15% (n=4) experienced G3-5 CRS and G3-5 neurotoxicity in the NBRT group, respectively. Overall treatment response in the bridging-RT and NBRT groups was 80% and 64%, respectively. The axi-cel CART product was associated with CRS (OR=26.67 p=.001) and CRS correlated with neurotoxicity (OR=12.22, p=.028). There was a trend towards an association for CRS with MTV (OR=1.06/mL, p=0.141) and TLG (OR=1.01/mL*SUV, p=0.099). Conclusions Bridging-RT prior to commercial CART does not appear to increase risk for CART-related toxicities or negatively impact outcomes in r/rABL patients. No G3 or higher RT-toxicities occurred in this series. Pre-treatment metabolic tumor burden may be associated with CART-associated CRS, however, larger patient numbers are required to elucidate significant associations. Future work to prospectively assess the value of bridging-RT is warranted.