PHASE 1 RESULTS OF ZUMA-4: KTE-X19, AN ANTI-CD19 CHIMERIC ANTIGEN RECEPTOR T CELL THERAPY, IN PEDIATRIC AND ADOLESCENT PATIENTS WITH RELAPSED/REFRACTORY B CELL ACUTE LYMPHOBLASTIC LEUKEMIA
Author(s): ,
Alan S. Wayne
Affiliations:
Children’s Hospital Los Angeles, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California,Los Angeles,United States
,
Van Huynh
Affiliations:
CHOC Children’s Hospital,Orange,United States
,
Nobuko Hijiya
Affiliations:
Lurie Children's Hospital of Chicago,Chicago,United States
,
Rayne Rouce
Affiliations:
Texas Children’s Hospital,Houston,United States
,
Patrick A. Brown
Affiliations:
Johns Hopkins University School of Medicine,Baltimore,United States
,
Joerg Krueger
Affiliations:
The Hospital for Sick Children, University of Toronto,Ontario,Canada
,
Michael Rytting
Affiliations:
University of Texas MD Anderson Cancer Center,Houston,United States
,
Carrie L. Kitko
Affiliations:
Vanderbilt University Medical Center,Nashville,United States
,
Edward Dela Ziga
Affiliations:
University of Miami Miller School of Medicine,Miami,United States
,
Michelle Hermiston
Affiliations:
University of California San Francisco,San Fransico,United States
,
Michael K. Richards
Affiliations:
Children’s Minnesota,Minneapolis,United States
,
Andre Baruchel
Affiliations:
Hôpital Universitaire Robert Debré (APHP) and University Paris Diderot,Paris,France
,
Tong Shen
Affiliations:
Kite, a Gilead Company,Santa Monica,United States
,
Lovely Goyal
Affiliations:
Kite, a Gilead Company,Santa Monica,United States
,
Remus Vezan
Affiliations:
Kite, a Gilead Company,Santa Monica,United States
,
Rajul Jain
Affiliations:
Kite, a Gilead Company,Santa Monica,United States
Daniel W. Lee
Affiliations:
University of Virginia,Charlottesville,United States
EHA Library. S. Wayne A. Jun 15, 2019; 267263; PS962
Alan S. Wayne
Alan S. Wayne
Contributions
Abstract

Abstract: PS962

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

Background
KTE-X19, formerly KTE-C19, is an autologous anti-CD19 chimeric antigen receptor T cell therapy. Early clinical experience with KTE-X19 in children and adolescents with relapsed/refractory B cell acute lymphoblastic leukemia is promising. Here, we present end of Phase 1 results from ZUMA-4.

Aims
Evaluate the safety and efficacy of KTE-X19 in pediatric and adolescent patients with relapsed/refractory B cell acute lymphoblastic leukemia.

Methods
In this dose-finding study, patients aged 2–21 years with relapsed/refractory B cell acute lymphoblastic leukemia (Philadelphia chromosome-positive allowed) and > 5% bone marrow blasts received either 2 or 1 × 106 chimeric antigen receptor T cells/kg following conditioning chemotherapy. The primary endpoint was incidence of dose-limiting toxicities. Secondary endpoints included complete remission (CR) rate (CR and CR with incomplete hematologic recovery [CR + CRi]) and overall survival. KTE-X19 formulation was optimized in a second 1 × 106 dose group using a lower infusion volume (40-mL versus 68-mL).

Results
As of October 11, 2018, 24 patients received KTE-X19 (median age of 13 years [range, 3-20 years]; 42% ≥ 3 prior regimens; 29% primary refractory disease; 25% relapsed/refractory post-allogeneic stem cell transplantation; 37% [range, 0%–100%], median preconditioning bone marrow blast count). The median follow-up was 13.2 months. Four patients received a targeted 2 × 106 cells/kg with no dose limiting toxicities in evaluable patients (n = 3). Patients were then enrolled at a targeted 1 × 106 cells/kg to improve the overall safety profile: 11 received the 68-mL formulation, and 9 received the 40-mL. Overall, the most common Grade ≥ 3 adverse events were hypotension (50%) and anemia (33%). Rates of Grade ≥ 3 neurologic events were 25%, 36%, and 11% in the 2 × 106, 1 × 106 (68-mL), and 1 × 106 (40-mL) groups, respectively, and rates of Grade ≥ 3 cytokine release syndrome were 75%, 18%, and 22%. Overall, there were 3 Grade 5 adverse events that were unrelated to KTE-X19. All but 2 patients in the 40-mL, 1 × 106 group were evaluable for efficacy with ≥ 2 months of follow-up. The CR + CRi rate was 100%, 64%, and 71% in the 2 × 106, 1 × 106 (68-mL), and 1 × 106 (40-mL) groups, respectively, with 25%, 71%, and 100% of CR + CRi patients in ongoing response as of the data cutoff; and 75%, 73%, and 86% of all patients had undetectable minimal residual disease. Median overall survival was not reached for either 1 × 106 group and was 8 months for the 2 × 106 group. Chimeric antigen receptor T cell expansion was observed in all dose/formulation groups.

Conclusion
Children and adolescents with relapsed/refractory B cell acute lymphoblastic leukemia achieved high minimal residual disease-negative remission rates with a manageable safety profile and promising efficacy after a single dose of KTE-X19. Phase 2 of ZUMA-4 is ongoing at the 40-mL, 1 × 106 cells/kg dose.

Session topic: 2. Acute lymphoblastic leukemia - Clinical

Keyword(s): Cancer immunotherapy, CD19, Non-Hodgkin's lymphoma

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