The autologous anti-CD19 CAR T cell therapy KTE-X19 appears safe and had encouraging efficacy as a treatment for patients with relapsed/refractory acute lymphoblastic leukemia, according to updated phase 1 results from ZUMA-3 presented at the 2019 ASCO Annual Meeting.

ZUMA-3 enrolled patients for CAR T cell therapy at a starting dose of 2 x 106 cells/kg to assess dose-limiting toxicity. Additional patients were enrolled at 2 x 106, 1 x 106 and 0.5 x 106 cells/kg. All included patients had to have greater than 5% bone marrow blasts; adequate renal, hepatic, and cardiac function; and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

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In total, 54 patients were enrolled and underwent leukapheresis; 49 continued on to conditioning chemotherapy; and 45 receiving KTE-X19.

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No dose-limiting toxicities occurred in the 3 patients who were evaluable for dose-limiting toxicities. Two patients experienced grade 5 KTE-X19-related adverse events during the study: 1 from multiorgan failure secondary to cytokine release syndrome and 1 who developed a stroke after infusion in the context of cytokine release syndrome and neurologic events. No cerebral edema occurred.

At all doses, 93% of patients experienced cytokine release syndrome with 29% being grade 3 or worse. Neurologic events occurred in 78% of patients, with 38% being grade 3 or worse.

The researchers revised the adverse event management guidelines for patients receiving doses of 1 x 106. Tocilizumab was not administered for neurologic events unless they occurred in the context of cytokine release syndrome, and steroids were initiated for grade 2 neurologic events compared with grade 3 previously.

With this revised strategy, improved safety was observed. No grade 4 or worse cytokines release syndrome or neurologic events occurred and the median duration of neurologic events was shorter in those receiving this revised management.

Final efficacy results showed that 68% of patients had a complete response or a complete response with incomplete hematologic recovery. At the 1 x 106 dose, the combined complete response rate was 84%. Of the 16 patients who achieved a complete response in the 1 x 106 dose group, 75% have ongoing responses.

Based on these data, the recommended phase 2 dose is 1 x 106 cells/kg with the modified adverse event management guidelines.


Shah BD, Bishop MR, Oluwqole OO, et al.. End of phase 1 results of ZUMA-3, a phase ½ study of KTE-X19, antiCD19 chimeric antigen receptor (CAR) T cell therapy, in adult patients (pts) with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL). Presented at: 2019 ASCO Annual Meeting; May 31-June 3, 2019; Chicago, IL. Abstract 7006.