Outcomes of Bridging and Salvage Radiotherapy in Relapsed or Refractory Mantle Cell Lymphoma Patients Undergoing CD19-Targeted CAR T-Cell Therapy.

Abstract

We sought to describe our early experience of using bridging and salvage radiation therapy (RT) in patients with relapsed/refractory mantle cell lymphoma (MCL) undergoing CD19-targeted chimeric antigen receptor (CAR) T-cell therapy. A retrospective study was conducted for consecutive MCL patients who were treated with commercially available CD19-targeted CAR T-cell therapy between 2020 and 2022 at a single institution. Patients who received RT pre-and post-CAR T-cell therapy were identified and analyzed using descriptive and statistical analysis. Overall survival (OS) from the date of CAR T infusion was estimated with the Kaplan-Meier method. The duration of local control (LC) was defined as the time between the start date of RT and the date of in-field progression/relapse. Response to RT was analyzed based on the total number of irradiated sites. A total of 21 patients with MCL who received CD19-targeted CAR T-cell therapy were identified (17 brexu cel, 3 tisa-cel, and 1 liso-cel) with a median follow-up of 15.3 months (24 days-36.2 months). The median age was 65 years at time of apheresis (43-83 years). The median OS for the entire cohort following CAR T-cell therapy was 17 months (95% CI: 14.2 months-not reached). Of the 21 patients, 1 patient received bridging RT prior to CAR T infusion, 1 patient received RT pre-and post-CAR T, and 5 patients received salvage RT post-CAR T with a total of 23 irradiated sites. Sites of RT include: extremities (10), central nervous system (3), pelvis/groin (3), head and neck (3), chest (2), abdomen (1), and multiple sites (1). The median dose/fractionation were 16.5 Gy (range, 3.6-45 Gy) and 5.5 fractions (range, 2-16 fractions)- radiation data was incomplete only for 1 patient who received RT at an outside institution. The in-field responses of the 21 evaluable sites were as follows: complete response (CR) (n = 18, 86%) and partial response (PR) (n = 3, 14%), translating into an LC rate of 100%; the remaining 2 sites were not evaluable since the patient died shortly after receiving RT due to progressive lymphoma. Notably, there was no correlation between RT dose and LC; 9 sites received low-dose RT (3.6-6 Gy) with responses as follows: CR (n = 6, 67%) and PR (n = 3, 33%). Only 1 patient experienced grade 3-4 RT-related toxicities. At the time of the last follow-up, 4 patients remained alive, and 3 patients succumbed to progressive lymphoma. As no studies exclusively focusing on CAR T-cell therapy and bridging or salvage RT have been published among relapsed/refractory MCL patients, our early experience underlines that using RT as a bridging and salvage approach is associated with excellent in-field control and limited toxicity in the peri-CAR T setting. Low-dose RT for MCL appears to be very effective in this highly refractory population and warrants further investigation.