KTE-X19, AN ANTI-CD19 CHIMERIC ANTIGEN RECEPTOR T CELL THERAPY, IN ADULT PATIENTS WITH RELAPSED/REFRACTORY ACUTE LYMPHOBLASTIC LEUKEMIA: END OF PHASE 1 RESULTS OF ZUMA-3
Author(s): ,
Bijal D. Shah
Affiliations:
Moffitt Cancer Center,Tampa,United States
,
Michael R. Bishop
Affiliations:
The University of Chicago Medicine,Chicago,United States
,
Olalekan O. Oluwole
Affiliations:
Vanderbilt-Ingram Cancer Center,Nashville,United States
,
Aaron C. Logan
Affiliations:
Helen Diller Comprehensive Cancer Center, University of California San Francisco,San Francisco,United States
,
Maria R. Baer
Affiliations:
University of Maryland Greenebaum Comprehensive Cancer Center,Baltimore,United States
,
William B. Donnellan
Affiliations:
Sarah Cannon Research Institute,Nashville,United States
,
Kristen M. O’Dwyer
Affiliations:
University of Rochester,Rochester,United States
,
Houston Holmes
Affiliations:
Texas Oncology-Baylor Charles A. Sammons Cancer Center,Dallas,United States
,
Martha L. Arellano
Affiliations:
Winship Cancer Institute of Emory University,Atlanta,United States
,
Armin Ghobadi
Affiliations:
Washington University School of Medicine and Siteman Cancer Center,St. Louis,United States
,
John M. Pagel
Affiliations:
Swedish Cancer Institute,Seattle,United States
,
Yi Lin
Affiliations:
Mayo Clinic,Rochester,United States
,
Ryan D. Cassaday
Affiliations:
University of Washington and Fred Hutchinson Cancer Research Center,Seattle,United States
,
Jae H. Park
Affiliations:
Memorial Sloan Kettering Cancer Center,New York,United States
,
Armen Mardiros
Affiliations:
Kite, a Gilead Company,Santa Monica,United States
,
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 K. Jain
Affiliations:
Kite, a Gilead Company,Santa Monica,United States
William G. Wierda
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
EHA Library. D. Shah B. Jun 15, 2019; 267246; PS945
Bijal D. Shah
Bijal D. Shah
Contributions
Abstract

Abstract: PS945

Type: Poster Presentation

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

Location: Poster area

Background
KTE-X19 is an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy under investigation for adult relapsed/refractory acute lymphoblastic leukemia. In an interim analysis of Phase 1 of ZUMA-3 (NCT02614066), we reported manageable safety and encouraging efficacy of KTE-X19; 72% of patients achieved a complete remission (CR) or CR with incomplete bone marrow recovery (CRi; Wierda et al, ASH 2018. #897).

Aims
The aim of this report is to present end of Phase 1 results of ZUMA-3.

Methods
Adults with relapsed/refractory B cell acute lymphoblastic leukemia, greater than 5% bone marrow blasts, and an Eastern Cooperative Oncology Group performance status of 0–1 received 2 × 106, 1 × 106, or 0.5 × 106 KTE-X19 cells/kg after conditioning chemotherapy. Revised adverse event (AE) management was implemented for additional patients in a 1 × 106 dose cohort: corticosteroids were given earlier at onset of Grade ≥ 2 neurologic events (NEs) and tocilizumab was used only for active toxicity. The primary endpoint was the rate of dose-limiting toxicities (DLTs). Key additional endpoints were KTE-X19 levels, incidence of AEs, minimal residual disease, and CR/CRi rate. 

Results
As of 9/27/18, 45 patients had received KTE-X19, with a median follow-up of 16 months. The median age was 46 years (range, 18–77 years); 30 patients (66%) had ≥ 3 prior therapies, and the median bone marrow blasts before conditioning chemotherapy was 70% (range, 0%–97%). Six, 23, and 16 patients received 2 × 106, 1 × 106, and 0.5 × 106 KTE-X19 cells/kg, respectively. There were no DLTs in the DLT-evaluable patients. The most common Grade ≥ 3 AEs were hypotension (38%), pyrexia (38%), and thrombocytopenia (31%). There were 2 previously reported KTE-X19–related Grade 5 AEs of cerebral infarction and multiorgan failure, both in the context of cytokine release syndrome (CRS). Grade ≥ 3 CRS and NEs occurred in 13 (29%) and 17 (38%) patients, respectively. Of 41 patients with ≥ 2 months of follow-up, 68% had CR/CRi, and 73% had undetectable minimal residual disease. Of 19 patients with ≥ 2 months of follow-up treated with 1 × 106 KTE-X19 cells/kg, 16 (84%) had a CR/CRi, and the median event-free survival was 15 months. In 9 patients treated with 1 × 106 KTE-X19 cells/kg who received revised AE management, 2 (22%) had Grade 3 CRS, and 1 (11%) had Grade 3 NE, with no Grade 4/5 events.     

Conclusion
KTE-X19 dosing and safety management have been successfully refined by testing 3 cell doses and evaluating a new AE management guideline with altered corticosteroids/tocilizumab use for NEs/CRS. The pivotal Phase 2 portion of ZUMA-3 is ongoing at the 1 × 106 dose with revised AE management.

Session topic: 2. Acute lymphoblastic leukemia - Clinical

Keyword(s): Acute lymphoblastic leukemia, Cancer immunotherapy, CD19

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