Metabolic parameters predict survival and toxicity in chimeric antigen receptor T-cell therapy-treated relapsed/refractory large B-cell lymphoma.

Abstract

CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment for patients with relapsed/refractory large B-cell lymphoma (LBCL). However, data available concerning the impact of the prognostic value of quantitative 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) parameters on the CAR T-related outcomes and toxicities are limited. Therefore, we aimed to evaluate the predictive value of pre- and post-CAR T metabolic parameters on survival and toxicities following CAR T-cell therapy. Fifty-nine patients with PET/CT scans done pre-and post-CAR T infusion were retrospectively identified and analyzed in a single institution database of LBCL patients treated with commercial CD19-targeted CAR T-cell therapy. The median follow-up was 10.7months [interquartile range (IQR): 2.6-25.5months]. The overall response (complete response-CR and partial response) and CR rates post-CAR T were 76% (n=45) and 53% (n=31), respectively. On univariate analysis, low pre-CAR T total lesion glycolysis (TLG) and metabolic tumor volume (MTV) predicted improved overall response post-CAR T (OR=4.7, p=0.01, OR=9.5, p=0.03, respectively) and CR post-CAR T (OR=12.4, p=0.0004, OR=10.9, p=0.0001, respectively). High TLG pre-CAR T was correlated with cytokine release syndrome (CRS, OR=3.25, p=0.04). High MTV pre-CAR T was correlated with developing immune effector cell neurotoxicity syndrome (ICANS) events (OR=4.3, p=0.01), and high SUV pre-CAR T was associated with grade 3-4 neurological events (OR=12, p=0.01). High MTV/TLG/SUVmax post-CAR T were significantly associated with inferior Overall survival (OS). On multivariate analysis, high TLG pre-CAR T (HR=2.4, p=0.03), age ≥60 (HR=2.7, p=0.03), and bulky disease (≥5cm) at the time of apheresis (HR=2.5, p=0.02) were identified to be independent prognostic factors for inferior PFS. High MTV post-CAR T was identified as the most prognostic factor associated with inferior OS.