Park et al. describe the long-term effects of 19-28z CAR T cell therapy in adults with relapsed B-cell ALL in this phase 1 clinical trial. In patients with a low initial disease burden, CAR T therapy correlated with an increase in both median event-free and overall survival, as well as lower rates of cytokine release syndrome, compared to patients with a high disease burden, who saw only moderate anticancer effects. Peak CAR T cell expansion also correlated with complete remission with minimal residual disease.

Background CD19-specific chimeric antigen receptor (CAR) T cells induce high rates of initial response among patients with relapsed B-cell acute lymphoblastic leukemia (ALL) and long-term remissions in a subgroup of patients. Methods We conducted a phase 1 trial involving adults with relapsed B-cell ALL who received an infusion of autologous T cells expressing the 19-28z CAR at the Memorial Sloan Kettering Cancer Center (MSKCC). Safety and long-term outcomes were assessed, as were their associations with demographic, clinical, and disease characteristics. Results A total of 53 adults received 19-28z CAR T cells that were manufactured at MSKCC. After infusion, severe cytokine release syndrome occurred in 14 of 53 patients (26%; 95% confidence interval [CI], 15 to 40); 1 patient died. Complete remission was observed in 83% of the patients. At a median follow-up of 29 months (range, 1 to 65), the median event-free survival was 6.1 months (95% CI, 5.0 to 11.5), and the median overall survival was 12.9 months (95% CI, 8.7 to 23.4). Patients with a low disease burden (<5% bone marrow blasts) before treatment had markedly enhanced remission duration and survival, with a median event-free survival of 10.6 months (95% CI, 5.9 to not reached) and a median overall survival of 20.1 months (95% CI, 8.7 to not reached). Patients with a higher burden of disease (>/=5% bone marrow blasts or extramedullary disease) had a greater incidence of the cytokine release syndrome and neurotoxic events and shorter long-term survival than did patients with a low disease burden. Conclusions In the entire cohort, the median overall survival was 12.9 months. Among patients with a low disease burden, the median overall survival was 20.1 months and was accompanied by a markedly lower incidence of the cytokine release syndrome and neurotoxic events after 19-28z CAR T-cell infusion than was observed among patients with a higher disease burden. (Funded by the Commonwealth Foundation for Cancer Research and others; ClinicalTrials.gov number, NCT01044069 .).

Author Info: (1) From the Leukemia Service, Department of Medicine (J.H.P., C.S., P.M., R.J.B.), the Michael G. Harris Cell Therapy and Cell Engineering Facility (I.R., X.W., B

Author Info: (1) From the Leukemia Service, Department of Medicine (J.H.P., C.S., P.M., R.J.B.), the Michael G. Harris Cell Therapy and Cell Engineering Facility (I.R., X.W., B. Senechal, Y.W.), the Center for Cell Engineering (J.H.P., I.R., X.W., R.J.B., M.S.), and the Departments of Epidemiology and Biostatistics (M.G.), Pediatrics (K.J.C.), Neurology (B. Santomasso), Anesthesiology and Critical Care Medicine (E.M.), and Pathology (M.R.), Memorial Sloan Kettering Cancer Center, and the Department of Medicine, Joan and Sanford Weill Medical College of Cornell University (J.H.P., C.S., R.J.B.) - all in New York; and the Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center, Tampa, FL (M.D.). (2) From the Leukemia Service, Department of Medicine (J.H.P., C.S., P.M., R.J.B.), the Michael G. Harris Cell Therapy and Cell Engineering Facility (I.R., X.W., B. Senechal, Y.W.), the Center for Cell Engineering (J.H.P., I.R., X.W., R.J.B., M.S.), and the Departments of Epidemiology and Biostatistics (M.G.), Pediatrics (K.J.C.), Neurology (B. Santomasso), Anesthesiology and Critical Care Medicine (E.M.), and Pathology (M.R.), Memorial Sloan Kettering Cancer Center, and the Department of Medicine, Joan and Sanford Weill Medical College of Cornell University (J.H.P., C.S., R.J.B.) - all in New York; and the Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center, Tampa, FL (M.D.). (3) From the Leukemia Service, Department of Medicine (J.H.P., C.S., P.M., R.J.B.), the Michael G. Harris Cell Therapy and Cell Engineering Facility (I.R., X.W., B. Senechal, Y.W.), the Center for Cell Engineering (J.H.P., I.R., X.W., R.J.B., M.S.), and the Departments of Epidemiology and Biostatistics (M.G.), Pediatrics (K.J.C.), Neurology (B. Santomasso), Anesthesiology and Critical Care Medicine (E.M.), and Pathology (M.R.), Memorial Sloan Kettering Cancer Center, and the Department of Medicine, Joan and Sanford Weill Medical College of Cornell University (J.H.P., C.S., R.J.B.) - all in New York; and the Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center, Tampa, FL (M.D.). (4) From the Leukemia Service, Department of Medicine (J.H.P., C.S., P.M., R.J.B.), the Michael G. Harris Cell Therapy and Cell Engineering Facility (I.R., X.W., B. Senechal, Y.W.), the Center for Cell Engineering (J.H.P., I.R., X.W., R.J.B., M.S.), and the Departments of Epidemiology and Biostatistics (M.G.), Pediatrics (K.J.C.), Neurology (B. Santomasso), Anesthesiology and Critical Care Medicine (E.M.), and Pathology (M.R.), Memorial Sloan Kettering Cancer Center, and the Department of Medicine, Joan and Sanford Weill Medical College of Cornell University (J.H.P., C.S., R.J.B.) - all in New York; and the Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center, Tampa, FL (M.D.). (5) From the Leukemia Service, Department of Medicine (J.H.P., C.S., P.M., R.J.B.), the Michael G. Harris Cell Therapy and Cell Engineering Facility (I.R., X.W., B. Senechal, Y.W.), the Center for Cell Engineering (J.H.P., I.R., X.W., R.J.B., M.S.), and the Departments of Epidemiology and Biostatistics (M.G.), Pediatrics (K.J.C.), Neurology (B. Santomasso), Anesthesiology and Critical Care Medicine (E.M.), and Pathology (M.R.), Memorial Sloan Kettering Cancer Center, and the Department of Medicine, Joan and Sanford Weill Medical College of Cornell University (J.H.P., C.S., R.J.B.) - all in New York; and the Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center, Tampa, FL (M.D.). (6) From the Leukemia Service, Department of Medicine (J.H.P., C.S., P.M., R.J.B.), the Michael G. Harris Cell Therapy and Cell Engineering Facility (I.R., X.W., B. Senechal, Y.W.), the Center for Cell Engineering (J.H.P., I.R., X.W., R.J.B., M.S.), and the Departments of Epidemiology and Biostatistics (M.G.), Pediatrics (K.J.C.), Neurology (B. Santomasso), Anesthesiology and Critical Care Medicine (E.M.), and Pathology (M.R.), Memorial Sloan Kettering Cancer Center, and the Department of Medicine, Joan and Sanford Weill Medical College of Cornell University (J.H.P., C.S., R.J.B.) - all in New York; and the Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center, Tampa, FL (M.D.). (7) From the Leukemia Service, Department of Medicine (J.H.P., C.S., P.M., R.J.B.), the Michael G. Harris Cell Therapy and Cell Engineering Facility (I.R., X.W., B. Senechal, Y.W.), the Center for Cell Engineering (J.H.P., I.R., X.W., R.J.B., M.S.), and the Departments of Epidemiology and Biostatistics (M.G.), Pediatrics (K.J.C.), Neurology (B. Santomasso), Anesthesiology and Critical Care Medicine (E.M.), and Pathology (M.R.), Memorial Sloan Kettering Cancer Center, and the Department of Medicine, Joan and Sanford Weill Medical College of Cornell University (J.H.P., C.S., R.J.B.) - all in New York; and the Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center, Tampa, FL (M.D.). (8) From the Leukemia Service, Department of Medicine (J.H.P., C.S., P.M., R.J.B.), the Michael G. Harris Cell Therapy and Cell Engineering Facility (I.R., X.W., B. Senechal, Y.W.), the Center for Cell Engineering (J.H.P., I.R., X.W., R.J.B., M.S.), and the Departments of Epidemiology and Biostatistics (M.G.), Pediatrics (K.J.C.), Neurology (B. Santomasso), Anesthesiology and Critical Care Medicine (E.M.), and Pathology (M.R.), Memorial Sloan Kettering Cancer Center, and the Department of Medicine, Joan and Sanford Weill Medical College of Cornell University (J.H.P., C.S., R.J.B.) - all in New York; and the Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center, Tampa, FL (M.D.). (9) From the Leukemia Service, Department of Medicine (J.H.P., C.S., P.M., R.J.B.), the Michael G. Harris Cell Therapy and Cell Engineering Facility (I.R., X.W., B. Senechal, Y.W.), the Center for Cell Engineering (J.H.P., I.R., X.W., R.J.B., M.S.), and the Departments of Epidemiology and Biostatistics (M.G.), Pediatrics (K.J.C.), Neurology (B. Santomasso), Anesthesiology and Critical Care Medicine (E.M.), and Pathology (M.R.), Memorial Sloan Kettering Cancer Center, and the Department of Medicine, Joan and Sanford Weill Medical College of Cornell University (J.H.P., C.S., R.J.B.) - all in New York; and the Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center, Tampa, FL (M.D.). (10) From the Leukemia Service, Department of Medicine (J.H.P., C.S., P.M., R.J.B.), the Michael G. Harris Cell Therapy and Cell Engineering Facility (I.R., X.W., B. Senechal, Y.W.), the Center for Cell Engineering (J.H.P., I.R., X.W., R.J.B., M.S.), and the Departments of Epidemiology and Biostatistics (M.G.), Pediatrics (K.J.C.), Neurology (B. Santomasso), Anesthesiology and Critical Care Medicine (E.M.), and Pathology (M.R.), Memorial Sloan Kettering Cancer Center, and the Department of Medicine, Joan and Sanford Weill Medical College of Cornell University (J.H.P., C.S., R.J.B.) - all in New York; and the Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center, Tampa, FL (M.D.). (11) From the Leukemia Service, Department of Medicine (J.H.P., C.S., P.M., R.J.B.), the Michael G. Harris Cell Therapy and Cell Engineering Facility (I.R., X.W., B. Senechal, Y.W.), the Center for Cell Engineering (J.H.P., I.R., X.W., R.J.B., M.S.), and the Departments of Epidemiology and Biostatistics (M.G.), Pediatrics (K.J.C.), Neurology (B. Santomasso), Anesthesiology and Critical Care Medicine (E.M.), and Pathology (M.R.), Memorial Sloan Kettering Cancer Center, and the Department of Medicine, Joan and Sanford Weill Medical College of Cornell University (J.H.P., C.S., R.J.B.) - all in New York; and the Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center, Tampa, FL (M.D.). (12) From the Leukemia Service, Department of Medicine (J.H.P., C.S., P.M., R.J.B.), the Michael G. Harris Cell Therapy and Cell Engineering Facility (I.R., X.W., B. Senechal, Y.W.), the Center for Cell Engineering (J.H.P., I.R., X.W., R.J.B., M.S.), and the Departments of Epidemiology and Biostatistics (M.G.), Pediatrics (K.J.C.), Neurology (B. Santomasso), Anesthesiology and Critical Care Medicine (E.M.), and Pathology (M.R.), Memorial Sloan Kettering Cancer Center, and the Department of Medicine, Joan and Sanford Weill Medical College of Cornell University (J.H.P., C.S., R.J.B.) - all in New York; and the Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center, Tampa, FL (M.D.). (13) From the Leukemia Service, Department of Medicine (J.H.P., C.S., P.M., R.J.B.), the Michael G. Harris Cell Therapy and Cell Engineering Facility (I.R., X.W., B. Senechal, Y.W.), the Center for Cell Engineering (J.H.P., I.R., X.W., R.J.B., M.S.), and the Departments of Epidemiology and Biostatistics (M.G.), Pediatrics (K.J.C.), Neurology (B. Santomasso), Anesthesiology and Critical Care Medicine (E.M.), and Pathology (M.R.), Memorial Sloan Kettering Cancer Center, and the Department of Medicine, Joan and Sanford Weill Medical College of Cornell University (J.H.P., C.S., R.J.B.) - all in New York; and the Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center, Tampa, FL (M.D.). (14) From the Leukemia Service, Department of Medicine (J.H.P., C.S., P.M., R.J.B.), the Michael G. Harris Cell Therapy and Cell Engineering Facility (I.R., X.W., B. Senechal, Y.W.), the Center for Cell Engineering (J.H.P., I.R., X.W., R.J.B., M.S.), and the Departments of Epidemiology and Biostatistics (M.G.), Pediatrics (K.J.C.), Neurology (B. Santomasso), Anesthesiology and Critical Care Medicine (E.M.), and Pathology (M.R.), Memorial Sloan Kettering Cancer Center, and the Department of Medicine, Joan and Sanford Weill Medical College of Cornell University (J.H.P., C.S., R.J.B.) - all in New York; and the Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center, Tampa, FL (M.D.). (15) From the Leukemia Service, Department of Medicine (J.H.P., C.S., P.M., R.J.B.), the Michael G. Harris Cell Therapy and Cell Engineering Facility (I.R., X.W., B. Senechal, Y.W.), the Center for Cell Engineering (J.H.P., I.R., X.W., R.J.B., M.S.), and the Departments of Epidemiology and Biostatistics (M.G.), Pediatrics (K.J.C.), Neurology (B. Santomasso), Anesthesiology and Critical Care Medicine (E.M.), and Pathology (M.R.), Memorial Sloan Kettering Cancer Center, and the Department of Medicine, Joan and Sanford Weill Medical College of Cornell University (J.H.P., C.S., R.J.B.) - all in New York; and the Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center, Tampa, FL (M.D.).

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