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OUTCOMES OF PATIENTS WITH RELAPSED/REFRACTORY ACUTE LYMPHOBLASTIC LEUKEMIA TREATED WITH PRIOR BLINATUMOMAB IN ZUMA-3, A STUDY OF KTE-C19, AN ANTI-CD19 CHIMERIC ANTIGEN RECEPTOR (CAR) T CELL THERAPY
Author(s): ,
Olalekan O. Oluwole
Affiliations:
Vanderbilt-Ingram Cancer Center,Nashville,United States
,
Bijal D. Shah
Affiliations:
Moffitt Cancer Center,Tampa,United States
,
Maria R. Baer
Affiliations:
University of Maryland, Greenebaum Comprehensive Cancer Center,Baltimore,United States
,
Michael R. Bishop
Affiliations:
The University of Chicago Medicine,Chicago,United States
,
Houston Holmes
Affiliations:
Texas Oncology-Baylor Charles A. Sammons Cancer Center,Dallas,United States
,
Gary J. Schiller
Affiliations:
David Geffen School of Medicine at UCLA,Los Angeles,United States
,
William Donnellan
Affiliations:
Sarah Cannon Research Institute,Nashville,United States
,
Kristen M. O'Dwyer
Affiliations:
University of Rochester,Rochester,United States
,
Armen Mardiros
Affiliations:
Kite, a Gilead company,Santa Monica,United States
,
John M. Rossi
Affiliations:
Kite, a Gilead company,Santa Monica,United States
,
Tong Shen
Affiliations:
Kite, a Gilead company,Santa Monica,United States
,
Allen Xue
Affiliations:
Kite, a Gilead company,Santa Monica,United States
,
Rajul K. Jain
Affiliations:
Kite, a Gilead company,Santa Monica,United States
,
Remus Vezan
Affiliations:
Kite, a Gilead company,Santa Monica,United States
William G. Wierda
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
(Abstract release date: 05/17/18) EHA Library. O. Oluwole O. 06/17/18; 214484; S1569
Olalekan O. Oluwole
Olalekan O. Oluwole
Contributions
Abstract

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

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