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PHASE 2 RESULTS OF THE ZUMA-3 STUDY EVALUATING KTE-X19, AN ANTI-CD19 CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY, IN ADULT PATIENTS WITH RELAPSED/REFRACTORY B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA
Author(s): ,
Bijal D. Shah, MD
Affiliations:
Moffitt Cancer Center,Tampa, FL,United States
,
Armin Ghobadi, MD
Affiliations:
Washington University School of Medicine,St. Louis, MO,United States
,
Olalekan O. Oluwole, MD, MPH, MBBS
Affiliations:
Vanderbilt-Ingram Cancer Center,Nashville, TN,United States
,
Aaron C. Logan, MD, PhD
Affiliations:
UCSF Medical Center, San Francisco, CA,United States
,
Nicolas Boissel, MD, PhD
Affiliations:
Hôpital Saint-Louis,Paris,France
,
Ryan D. Cassaday, MD
Affiliations:
University of Washington School of Medicine, Fred Hutchinson Cancer Research Center and Seattle Cancer Care Alliance,Seattle, WA,United States
,
Edouard Forcade, MD, PhD
Affiliations:
Centre Hospitalier Universitaire de Bordeaux,Pessac,France
,
Michael R. Bishop, MD
Affiliations:
The University of Chicago Medicine,Chicago, IL,United States
,
Max S. Topp, MD
Affiliations:
Universitätsklinikum Würzburg,Würzburg,Germany
,
Dimitrios Tzachanis, MD, PhD
Affiliations:
University of California, San Diego,San Diego, CA,United States
,
Kristen M. O'Dwyer, MD
Affiliations:
Wilmot Cancer Institute of University of Rochester,Rochester, NY,United States
,
Martha L. Arellano, MD
Affiliations:
Emory University School of Medicine,Atlanta, GA,United States
,
Yi Lin, MD, PhD
Affiliations:
Mayo Clinic,Rochester, MN,United States
,
Maria R. Baer, MD
Affiliations:
University of Maryland Marlene and Stewart Greenebaum Cancer Center,Baltimore, MD,United States
,
Gary J. Schiller, MD
Affiliations:
David Geffen School of Medicine at UCLA,Los Angeles, CA,United States
,
Jinghui Dong, PhD
Affiliations:
Kite, a Gilead Company,Santa Monica, CA,United States
,
Tong Shen, PhD
Affiliations:
Kite, a Gilead Company,Santa Monica, CA,United States
,
Francesca Milletti, PhD
Affiliations:
Kite, a Gilead Company,Santa Monica, CA,United States
,
Behzad Kharabi Masouleh, MD
Affiliations:
Kite, a Gilead Company,Santa Monica, CA,United States
Roch Houot, MD, PhD
Affiliations:
Centre Hospitalier Universitaire de Rennes,Rennes,France
EHA Library. Shah G. 06/09/21; 324525; S117
Gunjan Shah
Gunjan Shah
Contributions
Abstract
Presentation during EHA2021: All Oral presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: S117

Type: Oral Presentation

Session title: ALL - CAR-T: Alternative targets and age groups

Background
ZUMA-3 is a Phase 1/2 multicenter study evaluating KTE-X19, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). Phase 1 efficacy results at the recommended Phase 2 dose (1×106 CAR T cells/kg) were encouraging (Shah et al. J Clin Oncol. 2019;37[suppl, abstr]:7006). 

Aims
To present the pivotal Phase 2 results of ZUMA-3.

Methods
Eligible adults had R/R B-ALL, >5% bone marrow blasts by local evaluation, and Eastern Cooperative Oncology Group performance status of 0–1. Patients received a single infusion of KTE-X19 after conditioning chemotherapy. The primary endpoint was the overall complete remission (CR) rate (CR + CR with incomplete hematologic recovery [CRi]) by central review. Key secondary endpoints were duration of remission, relapse-free survival, overall survival, measurable residual disease negativity rate by flow cytometry, and safety. Data are reported in all treated patients.

Results
As of 9/2020, 55 of 71 enrolled patients received KTE-X19, with a median follow-up of 16.4 months (range, 10.3–22.1). Adverse events (n=8) and ineligibility (n=4) were the most common reasons enrolled patients did not receive KTE-X19 infusion. Median age was 40 years (range, 19–84); median bone marrow blasts at screening were 65% (range, 5–100); and 47% of patients had ≥3 prior therapies, with 45%, 22%, and 42% having previously received blinatumomab, inotuzumab ozogamicin, or allogeneic stem cell transplant, respectively.

 


The CR + CRi rate was 71% (95% CI, 57–82; 56% CR, 15% CRi); 31% of responders had ongoing responses. Medians (95% CI) for duration of remission, relapse-free survival, and overall survival were 12.8 months (8.7–not estimable), 11.6 months (2.7–15.5), and 18.2 months (15.9–not estimable), respectively. In responders, medians (95% CI) for relapse-free survival and overall survival were 14.2 months (11.6–not estimable) and not reached (16.2–not estimable). The measurable residual disease negativity rate was 97% among patients with CR + CRi. Among 25 patients with prior blinatumomab treatment, the CR + CRi rate was 60%. Ten patients (18%) received subsequent allogeneic stem cell transplant at a median of 98 days post–KTE-X19 infusion. Median duration of remission remained unchanged when not censoring for allogeneic stem cell transplant.


 


Grade ≥3 adverse events occurred in 95% of patients, most commonly anemia (49%) and neutropenia (49% [febrile 13%]). Grade ≥3 cytokine release syndrome (per Lee et al. [Blood. 2014;124:188-195]) and neurologic events occurred in 24% and 25% of patients, respectively, and were generally reversible. Two Grade 5 KTE-X19–related events occurred (brain herniation, n=1; septic shock, n=1). Median times to onset of cytokine release syndrome and neurologic events were 5 days and 9 days, with median durations of 7.5 days and 7 days, respectively. Median peak CAR T-cell levels (cells/µL) were 40.5 (range, 1.3–1533.4) in patients with CR and 0 in nonresponders. CAR T cells were undetectable by 9 months in ongoing responders.

Conclusion
After a median follow-up of 16.4 months, KTE-X19 demonstrated compelling clinical benefit in heavily pretreated adults with R/R B-ALL, with the median overall survival not yet reached for responding patients and a manageable safety profile.

Keyword(s): Acute lymphoblastic leukemia, Adult, CAR-T, Clinical trial

Presentation during EHA2021: All Oral presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: S117

Type: Oral Presentation

Session title: ALL - CAR-T: Alternative targets and age groups

Background
ZUMA-3 is a Phase 1/2 multicenter study evaluating KTE-X19, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). Phase 1 efficacy results at the recommended Phase 2 dose (1×106 CAR T cells/kg) were encouraging (Shah et al. J Clin Oncol. 2019;37[suppl, abstr]:7006). 

Aims
To present the pivotal Phase 2 results of ZUMA-3.

Methods
Eligible adults had R/R B-ALL, >5% bone marrow blasts by local evaluation, and Eastern Cooperative Oncology Group performance status of 0–1. Patients received a single infusion of KTE-X19 after conditioning chemotherapy. The primary endpoint was the overall complete remission (CR) rate (CR + CR with incomplete hematologic recovery [CRi]) by central review. Key secondary endpoints were duration of remission, relapse-free survival, overall survival, measurable residual disease negativity rate by flow cytometry, and safety. Data are reported in all treated patients.

Results
As of 9/2020, 55 of 71 enrolled patients received KTE-X19, with a median follow-up of 16.4 months (range, 10.3–22.1). Adverse events (n=8) and ineligibility (n=4) were the most common reasons enrolled patients did not receive KTE-X19 infusion. Median age was 40 years (range, 19–84); median bone marrow blasts at screening were 65% (range, 5–100); and 47% of patients had ≥3 prior therapies, with 45%, 22%, and 42% having previously received blinatumomab, inotuzumab ozogamicin, or allogeneic stem cell transplant, respectively.

 


The CR + CRi rate was 71% (95% CI, 57–82; 56% CR, 15% CRi); 31% of responders had ongoing responses. Medians (95% CI) for duration of remission, relapse-free survival, and overall survival were 12.8 months (8.7–not estimable), 11.6 months (2.7–15.5), and 18.2 months (15.9–not estimable), respectively. In responders, medians (95% CI) for relapse-free survival and overall survival were 14.2 months (11.6–not estimable) and not reached (16.2–not estimable). The measurable residual disease negativity rate was 97% among patients with CR + CRi. Among 25 patients with prior blinatumomab treatment, the CR + CRi rate was 60%. Ten patients (18%) received subsequent allogeneic stem cell transplant at a median of 98 days post–KTE-X19 infusion. Median duration of remission remained unchanged when not censoring for allogeneic stem cell transplant.


 


Grade ≥3 adverse events occurred in 95% of patients, most commonly anemia (49%) and neutropenia (49% [febrile 13%]). Grade ≥3 cytokine release syndrome (per Lee et al. [Blood. 2014;124:188-195]) and neurologic events occurred in 24% and 25% of patients, respectively, and were generally reversible. Two Grade 5 KTE-X19–related events occurred (brain herniation, n=1; septic shock, n=1). Median times to onset of cytokine release syndrome and neurologic events were 5 days and 9 days, with median durations of 7.5 days and 7 days, respectively. Median peak CAR T-cell levels (cells/µL) were 40.5 (range, 1.3–1533.4) in patients with CR and 0 in nonresponders. CAR T cells were undetectable by 9 months in ongoing responders.

Conclusion
After a median follow-up of 16.4 months, KTE-X19 demonstrated compelling clinical benefit in heavily pretreated adults with R/R B-ALL, with the median overall survival not yet reached for responding patients and a manageable safety profile.

Keyword(s): Acute lymphoblastic leukemia, Adult, CAR-T, Clinical trial

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