5-5-5 ABRT (Dose of 5 Gy per Fraction for up to 5 Fractions Over 5 Weeks Adaptive Bridging Radiation Therapy)-Artificial Intelligence Enters the CAR (-T) (Chimeric Antigen Receptor-T) in Relapsed/Refractory Large B Cell Lymphoma.

Purpose: Bridging radiation therapy (BRT) is effective for local control in patients with relapsed or refractory large B cell lymphoma who are undergoing chimeric antigen receptor (CAR) T cell therapy. We hypothesized that adaptive BRT (ABRT), which can be used to personalize the radiation dose, fractionation, and volume based on real-time lymphoma target volume, is feasible, safe, and effective for local control.

Methods And Materials: We conducted a pilot study to investigate, once weekly, computed tomography-based adaptive radiation therapy (Varian Ethos) at a dose of 5 Gy per fraction for up to 5 fractions over 5 weeks in patients referred for BRT (NCT06004167).

Results: Ten patients were enrolled. Eleven sites were irradiated for palliative purposes, achieving an overall symptomatic response rate of 100%. Of the 40 total ABRT sessions, 26 fractions were delivered (65%). For 8 of the 11 target volumes treated, ABRT was held after the first 1 or 2 fractions. The in-field responses during ABRT pre-CAR T were: complete response (n = 3, 30%), partial response (n = 6, 60%), and in-field progression (n = 1, 10%). After CAR T cell infusion, the best overall response rate was 70% (n = 7), all of whom achieved complete response. Among all 10 patients, 3 experienced in-field recurrence after start date of BRT. Among those with immune effector cell-associated neurotoxicity syndrome (n = 6), grade 3 immune effector cell-associated neurotoxicity syndrome occurred in 50% (n = 3). No grade 3 or higher cytokine release syndrome events were reported. At the time of the last follow-up, 9 patients (90%) were still alive, and 1 patient (10%) died due to disease progression.

Conclusions: We demonstrate the safety and feasibility of ABRT at a dose of 5 Gy per fraction for up to 5 fractions over 5 weeks in this highly relapsed/refractory population, even in patients with high-volume disease, with the vast majority responding to 1 to 2 fractions of 5 Gy. All patients achieved symptomatic relief and were able to proceed to CAR T cell infusion.