Contributions
Abstract: S1569
Type: Oral Presentation
Presentation during EHA23: On Sunday, June 17, 2018 from 09:00 - 09:15
Location: Room K1
Background
KTE-C19 showed promising efficacy (71% complete response [CR] or CR with incomplete hematologic recovery [CRi]) and manageable safety for patients with relapsed/refractory acute lymphoblastic leukemia (R/R ALL) in Phase 1 of ZUMA-3 (Shah ASH 2017; NCT02614066). Blinatumomab (blin), a CD19/CD3 bispecific T cell engager, is US FDA-approved for R/R ALL. The impact of prior blin on KTE-C19 efficacy is unknown.
Aims
To report responses to KTE-C19 in patients who received prior blin.
Methods
All patients provided written informed consent. Eligible patients were aged ≥ 18 years with R/R ALL (Ph+ allowed), ≥ 5% bone marrow blasts (documented CD19+), and ECOG 0-1. Patients received 2, 1, or 0.5 × 106 CAR T cells/kg after low-dose conditioning chemotherapy. Patients who received the 2 × 106 dose could not have prior blin. Outcomes assessed included efficacy, safety, product characteristics, and levels of CAR T cells and cytokines in blood.
Results
As of July 31, 2017, 29 patients were evaluable for safety, 24 for efficacy. A total of 6, 14, and 9 safety-evaluable patients received 2, 1, and 0.5 × 106 CAR T cells/kg, respectively. Patients with (n = 11) vs without (n = 18) prior blin had worse performance status (ECOG 0: 27% vs 44%) and were more likely to be R/R to ≥ 2nd-line therapy (55% vs 28%). With ≥ 8 weeks of follow-up, 63% vs 75% of patients with vs without prior blin had CR or CRi, respectively. Overall, 88% (21/24) had minimal residual disease-negative remission (7/8 with vs 14/16 without prior blin). Of patients with vs without prior blin, 27% vs 28% had Grade ≥ 3 cytokine release syndrome and 36% vs 61% had Grade ≥ 3 neurologic events. KTE-C19 was manufactured successfully in both groups, with similar product characteristics (eg, CD4/CD8 ratio, % transduction). Patients with vs without prior blin had similar proportions of naïve (43% vs 36%) and effector memory (19% vs 20%) T cells. Postinfusion CAR T expansion was observed regardless of prior blin; peak CAR T cell levels occurred between Days 7 and 14 for both groups.
Conclusion
While potentially confounded by multiple factors, these data demonstrate that prior blin did not preclude manufacturing of efficacious products. KTE-C19 continues to show promising efficacy and manageable safety in patients with R/R CD19+ ALL independent of prior blin.
Session topic: 2. Acute lymphoblastic leukemia - Clinical
Keyword(s): Acute lymphoblastic leukemia, Cancer immunotherapy, CD19
Abstract: S1569
Type: Oral Presentation
Presentation during EHA23: On Sunday, June 17, 2018 from 09:00 - 09:15
Location: Room K1
Background
KTE-C19 showed promising efficacy (71% complete response [CR] or CR with incomplete hematologic recovery [CRi]) and manageable safety for patients with relapsed/refractory acute lymphoblastic leukemia (R/R ALL) in Phase 1 of ZUMA-3 (Shah ASH 2017; NCT02614066). Blinatumomab (blin), a CD19/CD3 bispecific T cell engager, is US FDA-approved for R/R ALL. The impact of prior blin on KTE-C19 efficacy is unknown.
Aims
To report responses to KTE-C19 in patients who received prior blin.
Methods
All patients provided written informed consent. Eligible patients were aged ≥ 18 years with R/R ALL (Ph+ allowed), ≥ 5% bone marrow blasts (documented CD19+), and ECOG 0-1. Patients received 2, 1, or 0.5 × 106 CAR T cells/kg after low-dose conditioning chemotherapy. Patients who received the 2 × 106 dose could not have prior blin. Outcomes assessed included efficacy, safety, product characteristics, and levels of CAR T cells and cytokines in blood.
Results
As of July 31, 2017, 29 patients were evaluable for safety, 24 for efficacy. A total of 6, 14, and 9 safety-evaluable patients received 2, 1, and 0.5 × 106 CAR T cells/kg, respectively. Patients with (n = 11) vs without (n = 18) prior blin had worse performance status (ECOG 0: 27% vs 44%) and were more likely to be R/R to ≥ 2nd-line therapy (55% vs 28%). With ≥ 8 weeks of follow-up, 63% vs 75% of patients with vs without prior blin had CR or CRi, respectively. Overall, 88% (21/24) had minimal residual disease-negative remission (7/8 with vs 14/16 without prior blin). Of patients with vs without prior blin, 27% vs 28% had Grade ≥ 3 cytokine release syndrome and 36% vs 61% had Grade ≥ 3 neurologic events. KTE-C19 was manufactured successfully in both groups, with similar product characteristics (eg, CD4/CD8 ratio, % transduction). Patients with vs without prior blin had similar proportions of naïve (43% vs 36%) and effector memory (19% vs 20%) T cells. Postinfusion CAR T expansion was observed regardless of prior blin; peak CAR T cell levels occurred between Days 7 and 14 for both groups.
Conclusion
While potentially confounded by multiple factors, these data demonstrate that prior blin did not preclude manufacturing of efficacious products. KTE-C19 continues to show promising efficacy and manageable safety in patients with R/R CD19+ ALL independent of prior blin.
Session topic: 2. Acute lymphoblastic leukemia - Clinical
Keyword(s): Acute lymphoblastic leukemia, Cancer immunotherapy, CD19