1122 - Radiation Therapy as a Bridging Strategy in CAR-T Cell Therapy and the Impact of Tumor Control Status at CAR-T Cell Infusion

T. Shimizuguchi¹, Y. Kanemasa², Y. Yagi², S. Hayakawa¹, K. Taguchi¹, K. Ito¹, K. Murofushi¹, Y. Sasaki², S. Nakamura², S. Matsuda², T. Shimoyama², T. Toya³, H. Shimizu³, Y. Najima³, T. Kobayashi³, N. Doki³, K. Haraguchi⁴, and Y. Okuyama⁴; ¹Department of Radiation Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan, ²Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan, ³Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan, ⁴Division of Transfusion and Cell Therapy, Tokyo Metropolitan Cancer and Infectious Diseases Center, Tokyo, Japan

Purpose/Objective(s): The role of CD19-targeted chimeric antigen receptor T cell (CAR-T) therapy for large B cell lymphoma (LBCL) is expanding, and there is growing interest in how it can be optimally combined with radiation therapy (RT). Tumor control status before a CAR-T infusion is an important, predictive factor of outcomes, but little is known whether tumor control status is important in patients receiving RT as bridging therapy. The present study aimed to evaluate the relationship of pre-CAR-T infusion tumor control status with therapeutic outcomes in RT recipients. Materials/

Methods: Patients who received CAR-T therapy for relapsed or refractory LBCL between June 2020 and November 2023 at a single, tertiary cancer center were identified, and those who received RT within four months before a CAR-T infusion were enrolled. RT was indicated mainly for localized disease after systemic treatment as bridging or for the palliation of local symptoms in accordance with the International Lymphoma Radiation Oncology Group guidelines. Patients were classified into a complete response/ partial response (CR/PR) group or a no-response, stable disease/ progressive disease (SD/PD) group by tumor control status at the time of the CAR-T infusion in accordance with the Lugano criteria. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Additionally, risk factors of local failure following RT were explored. Tumor size > 5 cm on CT obtained for RT planning was defined as bulky.
Results: Of 76 CAR-T recipients, 30 eligible patients with a median age of 55 years (range: 18-75) were identified. All the eligible patients received two or more (median: 3) systemic treatment regimens at the time of leukapheresis. A median dosage of RT 40 Gy (range: 9.3-50 Gy) was administered in equal, 2-Gy doses daily using an alpha/beta ratio of 10. Sixteen patients achieved CR/PR before CAR-T infusion, and 14 patients had SD/PD. At the 17-month median follow-up, the CR/PR cohort had significantly greater 1-year PFS (78% vs 18%; P < .001) and OS (94% vs 29%; P < .001) than the SD/PD cohort. Local tumor progression was observed in six patients, and all were within the planning target volume. Of these, four patients had only local recurrences. Bulky tumor was identified as a risk factor of local recurrence (P = 0.02). Two patients with a bulky tumor who received a higher radiation dosage (50 Gy in 25 fractions) experienced no local recurrence thereafter.
Conclusion: When RT is used as bridging for CAR-T therapy, the tumor control status before CAR-T infusion predicts the outcome. A higher RT dosage may be effective for controlling bulky tumors.