Conditioning Prior To Car T Cells Predicts Response And Survival In Pediatric/Young Adult Relapse/Refractory (R/R) B-All

Introduction CD19-specific CAR T cells have clinical benefit in patients (pts) with R/R B-ALL. Several factors have been associated with response: conditioning chemotherapy, CD4/8 ratio, and post infusion CAR T cell expansion. Objective Determine feasibility of a multi-center CD19-specific CAR (19-28z) T cell product for R/R B-ALL, toxicity following infusion, and analysis of factors for optimal response. Methods Pediatric/young adults with R/R B-ALL were eligible for infusion. Patients received cyclophosphamide-based (Cy) conditioning of high dose (HD; 3g/m2) or low dose (LD; 1.5g/m2) chemotherapy. Outcomes of interest were complete response (CR) and overall survival (OS). Variables considered were conditioning regimen (HD vs LD), pre-treatment disease burden (MRD vs morphologic), complete remission (CR) status, absolute lymphocyte count (ALC) change, and in vivo CAR T cell expansion. Results 25 pts were included; 17 pts received HD-Cy and 8 pts received LD-Cy prior to CAR T cells. Among evaluable pts (n=24), CR/CRi was demonstrated in 94% and 38% for HD-Cy vs LD-Cy cohorts respectively (p=0a01). OS was superior in the HD-Cy cohort as compared to the LD-Cy cohort (median OS = not reached; NR) vs. 4a7 months (p=0a004; Figure 1). Lymphodepletion (Delta ALC: prior/following Cy) was higher in the HD-Cy cohort as compared to the LD-Cy cohort (p in vivo CAR T cell expansion (peak CAR T cell vector copy number/ml) in peripheral blood was higher in the HD-Cy cohort as compared to the LD-Cy cohort (p=0a01; Figure 2). To less extent, disease burden prior to treatment with conditioning chemotherapy and CAR T cells impacted response. Disease response was 93% (13/14) in low disease burden group (MRD-cohort) compared to 50% (5/10) in the high disease burden group (morphologic cohort) (p=0a05). OS was also superior in the low disease burden group (median OS = NR) compared to high disease burden group (median OS = 4.3 months; p=0a01). Combined response for HD-Cy/MRD was 100% (12/12), HD-Cy/Morphologic 75% (3/4), LD-Cy/MRD 50% (1/2), and LD-Cy/Morphologic 33% (2/6). Grade III/IV toxicity occurred in 32% (8/25) of pts including severe cytokine release syndrome (sCRS) in 16% of pts and severe CAR-associated neurotoxicity in 28% of pts. Findings In this preliminary analysis we demonstrate that dose intensity of conditioning chemotherapy positively correlated with CR and OS for pts treated with CAR T cells and confirms, to a lesser extent, pre-treatment disease burden impacts both CR and OS.