Ps962 phase 1 results of zuma-4: kte-x19, an anti-cd19 chimeric antigen receptor t cell therapy, in pediatric and adolescent patients with relapsed/refractory b cell acute lymphoblastic leukemia

Please indicate where the abstract has been published before: This abstract has also been submitted to ASPHO 2019 Background: KTE‐X19, formerly KTE‐C19, is an autologous anti‐CD19 chimeric antigen receptor T cell therapy. Early clinical experience with KTE‐X19 in children and adolescents with relapsed/refractory B cell acute lymphoblastic leukemia is promising. Here, we present end of Phase 1 results from ZUMA‐4. Aims: Evaluate the safety and efficacy of KTE‐X19 in pediatric and adolescent patients with relapsed/refractory B cell acute lymphoblastic leukemia. Methods: In this dose‐finding study, patients aged 2–21 years with relapsed/refractory B cell acute lymphoblastic leukemia (Philadelphia chromosome‐positive allowed) and > 5% bone marrow blasts received either 2 or 1 × 10 6 chimeric antigen receptor T cells/kg following conditioning chemotherapy. The primary endpoint was incidence of dose‐limiting toxicities. Secondary endpoints included complete remission (CR) rate (CR and CR with incomplete hematologic recovery [CR + CRi]) and overall survival. KTE‐X19 formulation was optimized in a second 1 × 10 6 dose group using a lower infusion volume (40‐mL versus 68‐mL). Results: As of October 11, 2018, 24 patients received KTE‐X19 (median age of 13 years [range, 3–20 years]; 42% ≥ 3 prior regimens; 29% primary refractory disease; 25% relapsed/refractory post‐allogeneic stem cell transplantation; 37% [range, 0%–100%], median preconditioning bone marrow blast count). The median follow‐up was 13.2 months. Four patients received a targeted 2 × 10 6 cells/kg with no dose limiting toxicities in evaluable patients (n = 3). Patients were then enrolled at a targeted 1 × 10 6 cells/kg to improve the overall safety profile: 11 received the 68‐mL formulation, and 9 received the 40‐mL. Overall, the most common Grade ≥ 3 adverse events were hypotension (50%) and anemia (33%). Rates of Grade ≥ 3 neurologic events were 25%, 36%, and 11% in the 2 × 10 6 , 1 × 10 6 (68‐mL), and 1 × 10 6 (40‐mL) groups, respectively, and rates of Grade ≥ 3 cytokine release syndrome were 75%, 18%, and 22%. Overall, there were 3 Grade 5 adverse events that were unrelated to KTE‐X19. All but 2 patients in the 40‐mL, 1 × 10 6 group were evaluable for efficacy with ≥ 2 months of follow‐up. The CR + CRi rate was 100%, 64%, and 71% in the 2 × 10 6 , 1 × 10 6 (68‐mL), and 1 × 10 6 (40‐mL) groups, respectively, with 25%, 71%, and 100% of CR + CRi patients in ongoing response as of the data cutoff; and 75%, 73%, and 86% of all patients had undetectable minimal residual disease. Median overall survival was not reached for either 1 × 10 6 group and was 8 months for the 2 × 10 6 group. Chimeric antigen receptor T cell expansion was observed in all dose/formulation groups. Summary/Conclusion: Children and adolescents with relapsed/refractory B cell acute lymphoblastic leukemia achieved high minimal residual disease‐negative remission rates with a manageable safety profile and promising efficacy after a single dose of KTE‐X19. Phase 2 of ZUMA‐4 is ongoing at the 40‐mL, 1 × 10 6 cells/kg dose.