Greater tumor burden before CD19-targeted chimeric antigen receptor T-cell (CAR T) therapy predicts lower complete response rate and shorter overall survival (OS) in aggressive non-Hodgkin lymphoma (NHL). Recent patterns of failure studies identified lesion characteristics including size, SUV, and extranodal location as associated with post-CAR T failure.
Here we analyze the effect of bridging radiation-containing regimens (BRT) on pre-CAR T lesion- and patient-level characteristics and post-CAR T outcomes including patterns of failure.
Consecutive NHL patients irradiated between 30d pre-leukapheresis until CAR T infusion were reviewed. Metabolic tumor volume (MTV) was contoured with threshold SUV 4. First post-CAR T failures were categorized as pre-existing/new/mixed with respect to pre-CAR T disease, and in-field/marginal/distant with respect to BRT.
Forty-one patients with diffuse large B cell lymphoma (DLBCL; n=33), mantle cell (n=7) and Burkitt’s lymphoma (n=1) were identified. BRT significantly improved established high-risk parameters of post-CAR T progression including in-field median MTV (45.5 to 0.2cc; p<0.001) maximum SUV (18.1 to 4.4; p<0.001), diameter (5.5 to 3.2cm; p<0.001), and LDH (312 to 232; p=0.025). DLBCL patients with lower LDH post-BRT had improved progression-free survival (PFS; p=0.001). In DLBCL, first failures were new in 7/19, pre-existing in 5/19, and mixed in 7/19; with respect to BRT, 4/19 were in-field and 4/19 marginal. Post-CAR T survival was similar in patients with initially low vs. newly low MTV post-BRT using a statistically determined threshold of 16cc (PFS: 26 vs. 31mo; OS unreached for both).
BRT produced significant cytoreduction in diameter, SUV, MTV, and LDH, all predictors of poor post-CAR T outcomes. Similar progression-free and overall survival in patients with initially low MTV and those who newly achieved low MTV after BRT suggest BRT may “convert” poor-risk patients to better risk. In the future, response to BRT may allow for risk stratification and individualization of bridging strategies.

Copyright © 2022. Published by Elsevier Inc.