Contributions
Abstract: EP341
Type: E-Poster Presentation
Session title: Acute lymphoblastic leukemia - Clinical
Background
We present long-term Phase 1 results of ZUMA-4, a study of KTE-X19 autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in pediatric/adolescent patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL).
Aims
To evaluate the long-term safety and efficacy of KTE-X19 in pediatric/adolescent patients with R/R B-ALL.
Methods
Patients (aged 2–21 years) with R/R B-ALL (Philadelphia chromosome-positive allowed) and >5% bone marrow blasts received 2×106 or 1×106 CAR T cells/kg after conditioning chemotherapy. The primary endpoint was incidence of dose-limiting toxicities. KTE-X19 formulation was optimized in a second 1×106-dose group using a lower infusion volume (40-mL vs 68-mL).
Results
As of 9/9/2020, the median follow-up was 36.1 months (range, 24.0–53.9), with 24 patients (median age, 14 years [range, 3–20]) of 31 enrolled receiving KTE-X19. The median time from leukapheresis to KTE-X19 product release was 14 days. Four patients received 2×106 cells/kg, with no dose-limiting toxicities in evaluable patients (n=3). Additionally, the 1×106 cells/kg dose level was explored (68-mL, n=11; 40-mL, n=9). Overall, Grade ≥3 adverse events occurred in 100% of patients, most commonly hypotension (50%) and anemia (42%). Rates of Grade ≥3 neurologic events/cytokine release syndrome were 25%/75% (2×106), 27%/27% (1×106 [68-mL]), and 11%/22% (1×106 [40-mL]). All 4 Grade 5 events (B-ALL, n=2; disseminated mucormycosis, n=1; Escherichia sepsis, n=1) were considered unrelated to KTE-X19. Overall complete remission rates (complete remission plus complete remission with incomplete hematologic recovery) were 75%, 64%, and 67% in the 2×106, 1×106 (68-mL), and 1×106 (40-mL) groups, respectively. Of responding patients, 100% had undetectable minimal residual disease. Sixteen patients (2×106, n=2; 1×106 [68-mL], n=8; 1×106 [40-mL], n=6) underwent subsequent allogeneic stem cell transplantation (median, 2.3 months post–KTE-X19). In the 2×106, 1×106 (68-mL), and 1×106 (40-mL) groups, the medians for duration of response (months) were 4.14, 10.68, and not reached, respectively. The median overall survival was not reached for the 1×106 groups (24-month rate: 68-mL, 73%; 40-mL, 88%) and was 8 months for the 2×106 group. In the 1×106 40-mL group (selected as Phase 2 dose), the median peak (range) of CAR gene copies per microgram of DNA in blood was 2.5×104 (0–2.5×105); among responders in this group, CAR T cells were undetectable by 3 months post-infusion.
Conclusion
Treatment with KTE-X19 at the recommended Phase 2 dose led to high complete remission rates, with the median overall survival not yet reached and a manageable safety profile. Phase 2 of ZUMA-4 is enrolling pediatric patients with R/R B-ALL or non-Hodgkin lymphoma, including patients with minimal residual disease-positive disease and early relapse (<18 months) after first-line therapy.
Keyword(s): ALL, CAR-T, Pediatric, Relapsed acute lymphoblastic leukemia
Abstract: EP341
Type: E-Poster Presentation
Session title: Acute lymphoblastic leukemia - Clinical
Background
We present long-term Phase 1 results of ZUMA-4, a study of KTE-X19 autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in pediatric/adolescent patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL).
Aims
To evaluate the long-term safety and efficacy of KTE-X19 in pediatric/adolescent patients with R/R B-ALL.
Methods
Patients (aged 2–21 years) with R/R B-ALL (Philadelphia chromosome-positive allowed) and >5% bone marrow blasts received 2×106 or 1×106 CAR T cells/kg after conditioning chemotherapy. The primary endpoint was incidence of dose-limiting toxicities. KTE-X19 formulation was optimized in a second 1×106-dose group using a lower infusion volume (40-mL vs 68-mL).
Results
As of 9/9/2020, the median follow-up was 36.1 months (range, 24.0–53.9), with 24 patients (median age, 14 years [range, 3–20]) of 31 enrolled receiving KTE-X19. The median time from leukapheresis to KTE-X19 product release was 14 days. Four patients received 2×106 cells/kg, with no dose-limiting toxicities in evaluable patients (n=3). Additionally, the 1×106 cells/kg dose level was explored (68-mL, n=11; 40-mL, n=9). Overall, Grade ≥3 adverse events occurred in 100% of patients, most commonly hypotension (50%) and anemia (42%). Rates of Grade ≥3 neurologic events/cytokine release syndrome were 25%/75% (2×106), 27%/27% (1×106 [68-mL]), and 11%/22% (1×106 [40-mL]). All 4 Grade 5 events (B-ALL, n=2; disseminated mucormycosis, n=1; Escherichia sepsis, n=1) were considered unrelated to KTE-X19. Overall complete remission rates (complete remission plus complete remission with incomplete hematologic recovery) were 75%, 64%, and 67% in the 2×106, 1×106 (68-mL), and 1×106 (40-mL) groups, respectively. Of responding patients, 100% had undetectable minimal residual disease. Sixteen patients (2×106, n=2; 1×106 [68-mL], n=8; 1×106 [40-mL], n=6) underwent subsequent allogeneic stem cell transplantation (median, 2.3 months post–KTE-X19). In the 2×106, 1×106 (68-mL), and 1×106 (40-mL) groups, the medians for duration of response (months) were 4.14, 10.68, and not reached, respectively. The median overall survival was not reached for the 1×106 groups (24-month rate: 68-mL, 73%; 40-mL, 88%) and was 8 months for the 2×106 group. In the 1×106 40-mL group (selected as Phase 2 dose), the median peak (range) of CAR gene copies per microgram of DNA in blood was 2.5×104 (0–2.5×105); among responders in this group, CAR T cells were undetectable by 3 months post-infusion.
Conclusion
Treatment with KTE-X19 at the recommended Phase 2 dose led to high complete remission rates, with the median overall survival not yet reached and a manageable safety profile. Phase 2 of ZUMA-4 is enrolling pediatric patients with R/R B-ALL or non-Hodgkin lymphoma, including patients with minimal residual disease-positive disease and early relapse (<18 months) after first-line therapy.
Keyword(s): ALL, CAR-T, Pediatric, Relapsed acute lymphoblastic leukemia