1099 - Bridging Radiotherapy for Chimeric Antigen Receptor T-Cell Therapy in Relapsed/Refractory Multiple Myeloma
Presenter(s)
K. Daniels1, C. Costello2, A. R. Jeong1, P. Sanghvi3, and K. R. Tringale4; 1UC San Diego, La Jolla, CA, 2University of California San Diego, San Diego, CA, 3Assistant Dean for Admissions and Director, Learning Environment, UCSD SOM, La Jolla, CA, 4Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA
Purpose/Objective(s): Chimeric antigen receptor T-cell therapy (CAR-T) is an emerging treatment for relapsed/refractory multiple myeloma (RRMM). The manufacturing time for CAR-T often necessitates bridging therapy for symptom and disease control. Data on outcomes, toxicities, and optimal timing for radiotherapy (RT) relative to CAR-T in RRMM are limited. We hypothesized that RT prior to CAR-T would not increase CAR-T-associated toxicity and sought to describe patterns of disease failure.
Materials/Methods:
All patients with RRMM who received commercial BCMA-targeting CAR-T between 2021-2024 at a single institution were included. Patients who received RT before CAR-T were grouped by timing of most recent RT relative to apheresis: Group A (> 1 year prior), B (= 1 year prior), and C (after apheresis but before CAR-T). Patterns of disease failure were evaluated. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were defined as per the American Society for Transplantation and Cellular Therapy. Progression was defined as the time at which it was first documented by the treating provider. Kaplan Meier survival analyses were performed from time of apheresis.Results: Of 51 patients, 26 (51%) received cilta-cel, 25 (49%) received ide-cel. Most had CRS (43, 84%) and few had ICANS (7, 14%). 18 (35%) received RT, 2 for salvage post-CAR-T (180 and 693 days after apheresis). Of the 16 with RT pre-CAR-T (Group A n=4, B n=5, C n=7), most (10, 63%) received ide-cel. The most common RT regimen was 20Gy/10fx (n=9, 56%; range 8-30Gy) and all Group C received 20Gy (2-4Gy-per-fraction). Median number of irradiated sites was 4 (1-5) and most were treated to bone only (12, 75%; 1 lymph node [LN], 1 bone + LN, 2 bone + paramedullary). Median overall survival among those with RT pre-CAR-T was not reached (95%CI 19.6m-NA) and did not differ by RT timing (p=0.8). Median progression-free survival was 37.1 months (95%CI 21.9-NR) and did not differ by RT timing (p=0.8) or CAR-T product (p=0.1). Of 6 who progressed after CAR-T, 1 had a recurrent site only (LN), 1 had both recurrent and new sites (bony), and 4 had new sites (1 biochemical, 1 kidney + muscle, 1 liver, 1 LN). Only 1 patient failed at the irradiated site, a LN that received 20Gy/8fx (Group C). RT at any time pre-CAR-T was not associated with CRS or ICANS (chi-square p=0.2 and p=0.9, respectively). Timing of RT was also not associated with CRS or ICANS (Fisher’s p=0.6 and p=0.5, respectively).
Conclusion: This is one of few studies evaluating RT prior to CAR-T and disease failure patterns in patients with RRMM. We showed that RT pre-CAR-T was not associated with post-CAR-T toxicity. Most relapses were extramedullary, including the only in-RT-field failure, highlighting the challenge of potentiating T-cell infiltration in plasmacytomas. Further work is needed to compare outcomes to those who did not receive RT to better optimize bridging regimens.