Bridging radiotherapy before anti-CD19 CAR T-cell therapy for Large B-cell lymphoma – results from a single-center study

BACKGROUND: Radiotherapy (RT) with immunochemotherapy (ICT) followed by CAR T-cell therapy may have synergistic effects due to cytoreduction and enhancing antigen spread, thereby inducing anti-cancer immune responses. The aim of this study was to analyze retrospective comparative data on the use of RT prior to anti-CD19 directed CAR T-cell therapy with a special focus on cytoreduction and RT related side effects. METHODS: All patients aged ≥ 18 years with relapsed/ refractory Large B-Cell-lymphoma (r/r LBCL) treated with anti-CD19 CAR T-cell therapy in our institution from 05/ 2019-08/2023 were analyzed retrospectively, with the RT therapy group comprising all patients receiving RT with or without concomitant systemic therapy. The control (CO) group was manually matched on age, prior therapy lines and remission state at lymphodepletion. Post-RT tumor volumes (TV) were calculated for 6 out of 7 patients pre-CAR T and for 1 patient post-CAR T. Primary endpoints were reduction of TV and CAR T as well as RT related side effects. Secondary endpoints included overall survival (OS) and progression free survival (PFS). RESULTS: 8 patients receiving RT within 60 days prior to CAR T-cell infusion and 8 controls were included in the final analysis. 6 out of 8 patients received concomitant bridging therapy. RT alone or in combination with concomitant systemic therapy led to a significant reduction of TV (average reduction of 68%) within the radiated field from baseline to post RT (p = 0.028). The combination of RT and CAR T-cell therapy was not associated with an increased rate of CAR T related side effects or complications (cytokine release syndrome p = 0.6, immune effector cell-associated neurotoxicity p = 0.2, corticosteroid use p > 0.9, Tocilizumab use p > 0.9, transfer to intensive care unit p = 0.6). OS and PFS did not differ between the RT- and CO-group (OS p = 0.64, PFS p = 0.35). CONCLUSIONS: Our data indicate that RT is a feasible and effective way of cytoreduction before CAR T-cell therapy, also in combination with systemic chemotherapy. CLINICAL TRIAL NUMBER: Not applicable.