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Chimeric antigen receptor (CAR) T-cells are autologous genetically engineered T cells recognizing tumor surface antigens. CAR-T cell targeting CD19 antigen has transformed salvage approach in relapsed/refractory B-cell lymphomas, achieving high response rates and durable remissions. However, several issues still need to be resolved to further optimize outcomes. One this challenges is to identify the optimal therapeutic regimen to maintain disease control prior to infusion of anti-CD19 CAR T-cells, during the 4 weeks period of product manufacturing (so called bridging therapy). In this context, radiation therapy (RT) may be a valuable bridging therapy to CAR T-cell therapy, offering tumor control and reduced toxicity, especially when disease burden is limited. Preliminary data from retrospective analysis showed early evidence that RT can be safe and effective as a bridging treatment. Therefore, RT may have complementary immunomodulatory activity with CAR-T cells. Here we describe a case series of our patients affected by high grade non Hodgkin Lymphoma, receiving radiation as a bridge therapy to anti-CD19 CAR T-cells. 

Between August 2020 and July 2021, 7 patient (3 M, 4 F) received bridging radiation before antiCD19 CAR T-cells. Median age was 47 years (25-69). Patient were affected by Diffuse Large B cell Lymphoma relapsed and/or refractory to chemotherapy and autologous stem cell transplantation, with a median of 5 lines of prior therapy (2-12). All patients received 2 to 2.5 Gy/fraction to a median dose of 32.4 Gy (20-42) with extended field RT surrounding disease involvement. One patient received concurrent chemotherapy. Median time from the end of RT to CAR-T cell infusion was 39 day(16-66).

After the end of RT and before CAR-T cell infusion, 3/7 patient experienced haematological toxicities (1 grade III pancytopenia; 1 grade IV pancytopenia in the patient treated with concomitant chemotherapy), while 4/7 patients showed no significant toxicities. Disease assessment by PET-CT after RT in 6/7 patient, showed 5 complete remissions and 1 stable disease. At a median follow-up was 7.8 months (2–12) after CAR-T cell therapy, all patient are in complete remission.

RT can be considered as a safe and effective bridge approach to CAR-T cell therapy in patient affected by Diffuse Large B cell Lymphoma. Future investigation is warranted to optimize timing and dose of bridging radiation before CAR T therapy.