Outcomes following CAR-T therapy in adults with relapsed/refractory B-ALL according to prior inotuzumab exposure.

e18626 Background: Chimeric antigen receptor T-cell (CAR-T) therapy represents a novel approach to relapsed and refractory B cell acute lymphoblastic leukemia (B-ALL). Its use is associated with toxicity events, namely cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS). Inotuzumab ozogamicin (InO) is a CD22 antibody-drug conjugate that was approved in 2017 for the treatment of R/R B-ALL. We report on the association between prior InO exposure and outcomes following CAR-T therapy. Methods: Retrospective cohort analysis was done through TriNetX, aggregating de-identified patient data from multiple healthcare organizations. Patient cohorts were constructed using clinical codes including all individuals >18 years of age with a diagnosis of B-ALL who subsequently received CAR-T. Cohort analysis was run to evaluate the differences in event free survival (EFS) and overall survival (OS) from 1 to 1825 days. CRS/ICANS were the primary endpoint, while mortality, proxy measures of toxicity (tocilizumab use, ICU admission, etc.), and acute/subacute hepatic disease represented secondary endpoints. Results: A total of 148 patients with and 618 without prior InO exposure were identified. After propensity score matching patients for demographic factors, age at CAR-T administration, sex, and prior chemotherapy/HSCT, 124 patients remained per cohort. The hazard of CRS/ICANS after CAR-T administration was significantly increased in the InO cohort (HR = 1.48, 95% CI 1.04-2.10). Prior InO use was associated with an increased hazard of CAR-T toxicity proxy events (HR 2.41, 95% CI 1.80-3.24) as well as increased cumulative incidence (RR 1.34, 95% CI 1.17-1.53). Hepatic toxicity or disease events occurred in 49.1% of InO patients compared to 35.4% in non-Ino patients (HR 1.65, 95% CI 1.11-2.44). InO exposure was also associated with significantly worse OS after CAR-T (HR = 1.97, 95% CI 1.27-3.04). Conclusions: InO exposure prior to CAR-T was associated with higher rates of CRS/ICANS, hepatic toxicity, and increased mortality in the analyzed B-ALL cohorts. Increased mortality may reflect underlying disease severity and cumulative treatment exposure in patients receiving prior InO. Inotuzumab use may identify a subgroup predisposed to a higher rate of complications that would benefit from additional supportive measures and monitoring post CAR-T. Comparison of post-CAR-T outcomes in InO vs InO-free patients. Outcome Inotuzumab (n=124) No Inotuzumab (n=124) Measure of Association CRS/ICANS 72 55 HR 1.48 (1.04, 2.10) CAR-T Event Proxies 113 84 HR 2.41 (1.80, 3.24) Hepatic Toxicity 61 44 HR 1.62 (1.11, 2.44) Death 55 33 HR 1.97 (1.27, 3.04)