Treatment kinetics and local response during and after bridging radiotherapy prior to CAR-T cell therapy for lymphomas

Bridging radiotherapy (BR) prior to CAR-T for non-Hodgkin lymphoma (NHL) can achieve durable cytoreduction, but optimal dosing remains undefined. We evaluated correlates of local progression (LP) among 33 patients (25 large B-cell lymphoma [LBCL], 8 Mantle Cell Lymphoma [MCL]) with relapsed/refractory NHL who received BR at our institution. Using image-guided radiotherapy (IGRT), we defined 'rapid bridging response' (RBR) as ≥10% volume reduction within 5 fractions. We estimated the cumulative incidence of LP with death as a competing risk. Five of 19 LBCL and 5/7 MCL patients with IGRT experienced RBR. LP occurred in 6 patients (all LBCL, 18-month cumulative incidence 19%), none of whom had RBR, and was increased for tumors with metabolic tumor volume > 100 mL. Among LBCL patients, median volume change during radiation for tumors with LP was 0% vs -4% for those without. Histology, radiomic features, and real-time radiotherapy response may guide a personalized approach to BR.