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SUBGROUP ANALYSES OF KTE-X19, AN ANTI-CD19 CHIMERIC ANTIGEN RECEPTOR (CAR) T-CELL THERAPY, IN ADULT PATIENTS WITH RELAPSED OR REFRACTORY B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (R/R B-ALL) IN ZUMA-3
Author(s): ,
Bijal D. Shah
Affiliations:
Moffitt Cancer Center,Tampa, FL,États-unis;Moffitt Cancer Center,Tampa, FL,Vereinigte Staaten;Moffitt Cancer Center,Tampa, FL,Stati Uniti;Moffitt Cancer Center,Tampa, FL,United States;Moffitt Cancer Center,Tampa, FL,Estados Unidos;Moffitt Cancer Center,Tampa, FL,Verenigde Staten;Moffitt Cancer Center,Tampa, FL,Estados Unidos;Moffitt Cancer Center,Tampa, FL,United States;Moffitt Cancer Center,Tampa
,
Ryan D. Cassaday
Affiliations:
University of Washington, Fred Hutchinson, Seattle Cancer Care Alliance,Seattle WA,États-unis;University of Washington, Fred Hutchinson, Seattle Cancer Care Alliance,Seattle WA,Vereinigte Staaten;University of Washington, Fred Hutchinson, Seattle Cancer Care Alliance,Seattle WA,Stati Uniti;University of Washington, Fred Hutchinson, Seattle Cancer Care Alliance,Seattle WA,United States;University o
,
Jae H. Park
Affiliations:
Memorial Sloan Kettering Cancer Center,New York, NY,États-unis;Memorial Sloan Kettering Cancer Center,New York, NY,Vereinigte Staaten;Memorial Sloan Kettering Cancer Center,New York, NY,Stati Uniti;Memorial Sloan Kettering Cancer Center,New York, NY,United States;Memorial Sloan Kettering Cancer Center,New York, NY,Estados Unidos;Memorial Sloan Kettering Cancer Center,New York, NY,Verenigde Staten;
,
Roch Houot
Affiliations:
CHU Rennes, University Hospital Rennes, Inserm & EFS,Rennes,France;CHU Rennes, University Hospital Rennes, Inserm & EFS,Rennes,Frankreich;CHU Rennes, University Hospital Rennes, Inserm & EFS,Rennes,Francia;CHU Rennes, University Hospital Rennes, Inserm & EFS,Rennes,France;CHU Rennes, University Hospital Rennes, Inserm & EFS,Rennes,Francia;CHU Rennes, Univers
,
Olalekan O. Oluwole
Affiliations:
Vanderbilt University Cancer Center,Nashville, TN,États-unis;Vanderbilt University Cancer Center,Nashville, TN,Vereinigte Staaten;Vanderbilt University Cancer Center,Nashville, TN,Stati Uniti;Vanderbilt University Cancer Center,Nashville, TN,United States;Vanderbilt University Cancer Center,Nashville, TN,Estados Unidos;Vanderbilt University Cancer Center,Nashville, TN,Verenigde Staten;Vanderbilt U
,
Aaron C. Logan
Affiliations:
UCSF Medical Center,San Francisco, CA,États-unis;UCSF Medical Center,San Francisco, CA,Vereinigte Staaten;UCSF Medical Center,San Francisco, CA,Stati Uniti;UCSF Medical Center,San Francisco, CA,United States;UCSF Medical Center,San Francisco, CA,Estados Unidos;UCSF Medical Center,San Francisco, CA,Verenigde Staten;UCSF Medical Center,San Francisco, CA,Estados Unidos;UCSF Medical Center,San Francis
,
Nicolas Boissel
Affiliations:
Hôpital Saint-Louis,Paris,France;Hôpital Saint-Louis,Paris,Frankreich;Hôpital Saint-Louis,Paris,Francia;Hôpital Saint-Louis,Paris,France;Hôpital Saint-Louis,Paris,Francia;Hôpital Saint-Louis,Paris,Frankrijk;Hôpital Saint-Louis,Paris,França;Hôpital Saint-Louis,Paris,Франция ;Hôpital Saint-Louis,Paris,Frankrike
,
Thibaut Leguay
Affiliations:
Service d'hématologie clinique et thérapie cellulaire Hôpital du Haut-Leveque CHU de Bordeaux,Bordeaux,France;Service d'hématologie clinique et thérapie cellulaire Hôpital du Haut-Leveque CHU de Bordeaux,Bordeaux,Frankreich;Service d'hématologie clinique et thérapie cellulaire Hôpital du Haut-Leveque CHU de Bordeaux,Bordeaux,Francia;Service d'hématologie clinique et thérapie cellulaire Hôpital du
,
Michael R. Bishop
Affiliations:
The University of Chicago Medicine,Chicago, IL,États-unis;The University of Chicago Medicine,Chicago, IL,Vereinigte Staaten;The University of Chicago Medicine,Chicago, IL,Stati Uniti;The University of Chicago Medicine,Chicago, IL,United States;The University of Chicago Medicine,Chicago, IL,Estados Unidos;The University of Chicago Medicine,Chicago, IL,Verenigde Staten;The University of Chicago Medi
,
Max S. Topp
Affiliations:
Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg,Würzburg,Allemagne;Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg,Würzburg,Deutschland;Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg,Würzburg,Germania;Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg,Würzburg,Germany;Medizinische Klinik und Poliklinik II, Universitä
,
Dimitrios Tzachanis
Affiliations:
University of California San Diego,San Deigo, CA,États-unis;University of California San Diego,San Deigo, CA,Vereinigte Staaten;University of California San Diego,San Deigo, CA,Stati Uniti;University of California San Diego,San Deigo, CA,United States;University of California San Diego,San Deigo, CA,Estados Unidos;University of California San Diego,San Deigo, CA,Verenigde Staten;University of Cali
,
Kristen M. O'Dwyer
Affiliations:
Wilmot Cancer Institute of University of Rochester,Rochester, NY,États-unis;Wilmot Cancer Institute of University of Rochester,Rochester, NY,Vereinigte Staaten;Wilmot Cancer Institute of University of Rochester,Rochester, NY,Stati Uniti;Wilmot Cancer Institute of University of Rochester,Rochester, NY,United States;Wilmot Cancer Institute of University of Rochester,Rochester, NY,Estados Unidos;Wilm
,
Martha L. Arellano
Affiliations:
Winship Cancer Institute of Emory University,Atlanta, GA,États-unis;Winship Cancer Institute of Emory University,Atlanta, GA,Vereinigte Staaten;Winship Cancer Institute of Emory University,Atlanta, GA,Stati Uniti;Winship Cancer Institute of Emory University,Atlanta, GA,United States;Winship Cancer Institute of Emory University,Atlanta, GA,Estados Unidos;Winship Cancer Institute of Emory University
,
Yi Lin
Affiliations:
Mayo Clinic,Rochester, MN,États-unis;Mayo Clinic,Rochester, MN,Vereinigte Staaten;Mayo Clinic,Rochester, MN,Stati Uniti;Mayo Clinic,Rochester, MN,United States;Mayo Clinic,Rochester, MN,Estados Unidos;Mayo Clinic,Rochester, MN,Verenigde Staten;Mayo Clinic,Rochester, MN,Estados Unidos;Mayo Clinic,Rochester, MN,United States;Mayo Clinic,Rochester, MN,USA
,
Maria R. Baer
Affiliations:
University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center,Baltimore, MD,États-unis;University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center,Baltimore, MD,Vereinigte Staaten;University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center,Baltimore, MD,Stati Uniti;University of Maryland Marlene and Stewart Greenebaum Comprehensive Ca
,
Gary J. Schiller
Affiliations:
David Geffen School of Medicine at UCLA,Los Angeles, CA,États-unis; David Geffen School of Medicine at UCLA,Los Angeles, CA,Vereinigte Staaten; David Geffen School of Medicine at UCLA,Los Angeles, CA,Stati Uniti; David Geffen School of Medicine at UCLA,Los Angeles, CA,United States; David Geffen School of Medicine at UCLA,Los Angeles, CA,Estados Unidos; David Geffen School of Medicine at UCLA,Los
,
Marion Subklewe
Affiliations:
Ludwig-Maximilians-Universität München,Munich,Allemagne;Ludwig-Maximilians-Universität München,Munich,Deutschland;Ludwig-Maximilians-Universität München,Munich,Germania;Ludwig-Maximilians-Universität München,Munich,Germany;Ludwig-Maximilians-Universität München,Munich,Alemania;Ludwig-Maximilians-Universität München,Munich,Duitsland;Ludwig-Maximilians-Universität München,Munich,Alemanha;Ludwig-Maxi
,
Mehrdad Abedi
Affiliations:
University of California Davis Comprehensive Cancer Center,Sacramento, CA,États-unis;University of California Davis Comprehensive Cancer Center,Sacramento, CA,Vereinigte Staaten;University of California Davis Comprehensive Cancer Center,Sacramento, CA,Stati Uniti;University of California Davis Comprehensive Cancer Center,Sacramento, CA,United States;University of California Davis Comprehensive Can
,
Monique C. Minnema
Affiliations:
University Medical Center Utrecht, on behalf of HOVON/LLPC,Utrecht,Pays-bas;University Medical Center Utrecht, on behalf of HOVON/LLPC,Utrecht,Niederlande;University Medical Center Utrecht, on behalf of HOVON/LLPC,Utrecht,Paesi Bassi;University Medical Center Utrecht, on behalf of HOVON/LLPC,Utrecht,Netherland;University Medical Center Utrecht, on behalf of HOVON/LLPC,Utrecht,Países Bajos;Universi
,
William G. Wierda
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston, TX,États-unis;The University of Texas MD Anderson Cancer Center,Houston, TX,Vereinigte Staaten;The University of Texas MD Anderson Cancer Center,Houston, TX,Stati Uniti;The University of Texas MD Anderson Cancer Center,Houston, TX,United States;The University of Texas MD Anderson Cancer Center,Houston, TX,Estados Unidos;The University of T
,
Daniel J. DeAngelo
Affiliations:
Dana-Farber Cancer Institute,Boston, MA,États-unis;Dana-Farber Cancer Institute,Boston, MA,Vereinigte Staaten;Dana-Farber Cancer Institute,Boston, MA,Stati Uniti;Dana-Farber Cancer Institute,Boston, MA,United States;Dana-Farber Cancer Institute,Boston, MA,Estados Unidos;Dana-Farber Cancer Institute,Boston, MA,Verenigde Staten;Dana-Farber Cancer Institute,Boston, MA,Estados Unidos;Dana-Farber Cance
,
Patrick Stiff
Affiliations:
Loyola University Chicago Stritch School of Medicine,Maywood, IL,États-unis;Loyola University Chicago Stritch School of Medicine,Maywood, IL,Vereinigte Staaten;Loyola University Chicago Stritch School of Medicine,Maywood, IL,Stati Uniti;Loyola University Chicago Stritch School of Medicine,Maywood, IL,United States;Loyola University Chicago Stritch School of Medicine,Maywood, IL,Estados Unidos;Loyo
,
Deepa Jeyakumar
Affiliations:
University of California Irvine Medical Center,Irvine, CA,États-unis;University of California Irvine Medical Center,Irvine, CA,Vereinigte Staaten;University of California Irvine Medical Center,Irvine, CA,Stati Uniti;University of California Irvine Medical Center,Irvine, CA,United States;University of California Irvine Medical Center,Irvine, CA,Estados Unidos;University of California Irvine Medical
,
Jinghui Dong
Affiliations:
Kite, a Gilead Company,Santa Monica, CA,États-unis;Kite, a Gilead Company,Santa Monica, CA,Vereinigte Staaten;Kite, a Gilead Company,Santa Monica, CA,Stati Uniti;Kite, a Gilead Company,Santa Monica, CA,United States;Kite, a Gilead Company,Santa Monica, CA,Estados Unidos;Kite, a Gilead Company,Santa Monica, CA,Verenigde Staten;Kite, a Gilead Company,Santa Monica, CA,Estados Unidos;Kite, a Gilead Co
,
Sabina Adhikary
Affiliations:
Kite, a Gilead Company,Santa Monica, CA,États-unis;Kite, a Gilead Company,Santa Monica, CA,Vereinigte Staaten;Kite, a Gilead Company,Santa Monica, CA,Stati Uniti;Kite, a Gilead Company,Santa Monica, CA,United States;Kite, a Gilead Company,Santa Monica, CA,Estados Unidos;Kite, a Gilead Company,Santa Monica, CA,Verenigde Staten;Kite, a Gilead Company,Santa Monica, CA,Estados Unidos;Kite, a Gilead Co
,
Lang Zhou
Affiliations:
Kite, a Gilead Company,Santa Monica, CA,États-unis;Kite, a Gilead Company,Santa Monica, CA,Vereinigte Staaten;Kite, a Gilead Company,Santa Monica, CA,Stati Uniti;Kite, a Gilead Company,Santa Monica, CA,United States;Kite, a Gilead Company,Santa Monica, CA,Estados Unidos;Kite, a Gilead Company,Santa Monica, CA,Verenigde Staten;Kite, a Gilead Company,Santa Monica, CA,Estados Unidos;Kite, a Gilead Co
,
Petra C. Schuberth
Affiliations:
Kite, a Gilead Company,Santa Monica, CA,États-unis;Kite, a Gilead Company,Santa Monica, CA,Vereinigte Staaten;Kite, a Gilead Company,Santa Monica, CA,Stati Uniti;Kite, a Gilead Company,Santa Monica, CA,United States;Kite, a Gilead Company,Santa Monica, CA,Estados Unidos;Kite, a Gilead Company,Santa Monica, CA,Verenigde Staten;Kite, a Gilead Company,Santa Monica, CA,Estados Unidos;Kite, a Gilead Co
,
Behzad Kharabi Masouleh
Affiliations:
Kite, a Gilead Company,Santa Monica, CA,États-unis;Kite, a Gilead Company,Santa Monica, CA,Vereinigte Staaten;Kite, a Gilead Company,Santa Monica, CA,Stati Uniti;Kite, a Gilead Company,Santa Monica, CA,United States;Kite, a Gilead Company,Santa Monica, CA,Estados Unidos;Kite, a Gilead Company,Santa Monica, CA,Verenigde Staten;Kite, a Gilead Company,Santa Monica, CA,Estados Unidos;Kite, a Gilead Co
Armin Ghobadi
Affiliations:
Washington University School of Medicine,St Louis, MO,États-unis;Washington University School of Medicine,St Louis, MO,Vereinigte Staaten;Washington University School of Medicine,St Louis, MO,Stati Uniti;Washington University School of Medicine,St Louis, MO,United States;Washington University School of Medicine,St Louis, MO,Estados Unidos;Washington University School of Medicine,St Louis, MO,Veren
(Abstract release date: 05/12/22) EHA Library. D. Shah B. 06/10/22; 357219; P356
Bijal D. Shah
Bijal D. Shah
Contributions
Abstract
Presentation during EHA2022: All (e)Poster presentations will be made available as of Friday, June 10, 2022 (09:00 CEST) and will be accessible for on-demand viewing until Monday, August 15, 2022 on the Congress platform.

Abstract: P356

Type: Poster presentation

Session title: Acute lymphoblastic leukemia - Clinical

Background
Brexucabtagene autoleucel (KTE-X19) is approved in the US for the treatment of adult patients with R/R B-ALL based on the positive results of the ZUMA-3 study. In the pivotal Phase 2 portion of ZUMA-3, the overall complete remission (CR) rate (CR + CR with incomplete hematologic recovery [CRi]) was 71% (N=55; median follow-up 16.4 months; Shah et al. Lancet 2021).

Aims
To assess outcomes in ZUMA-3 by prior number of therapy lines, prior blinatumomab, prior allogeneic stem cell transplant (alloSCT), and subsequent alloSCT.

Methods
Eligible adults had R/R B-ALL and received a single infusion of KTE-X19 following leukapheresis and conditioning chemotherapy. Outcomes assessed by independent review are reported in all patients treated at the pivotal dose (1×106 CAR T cells/kg).

Results
As of 23 July 2021, the median follow-up among all treated patients in Phase 2 (N=55) was 26.8 months (range, 20.7-32.6). At baseline, 10 patients (18%) had 1 prior line of therapy, and 45 patients (82%) had ≥2 prior lines. The overall CR/CRi rates (95% CI) for patients with 1 or ≥2 prior lines of therapy were 90% (55-100) and 67% (51-80), respectively. In patients with 1 or ≥2 prior lines of therapy, the median (95% CI) duration of remission (DOR) was 4.7 months (1.8-not estimable [NE]) and 14.6 months (9.4-NE), and the median (95% CI) overall survival (OS) was not reached (NR) (2.1-NE) and 25.4 months (14.2-NE), respectively. Grade ≥3 cytokine release syndrome (CRS) occurred in 10% and 27% of patients with 1 or ≥2 prior lines of therapy, and Grade ≥3 neurologic events occurred in 30% and 24%, respectively.

Among the 25 patients (45%) who had prior blinatumomab at baseline, the overall CR/CRi rate (95% CI) was 60% (39-79), and 80% (61-92) in the 30 patients (55%) without prior blinatumomab. The median (95% CI) DOR was 19.1 months (1.3-NE) and 10.3 months (5.2-NE) in patients with or without prior blinatumomab, and the median (95% CI) OS was 14.2 months (3.2-26.0) and NR (18.6-NE), respectively. In patients with or without prior blinatumomab, rates of Grade ≥3 CRS were 24% and 23%, and rates of Grade ≥3 neurologic events were 20% and 30%, respectively.

The overall CR/CRi rate in the 23 patients (42%) who had prior alloSCT vs the 32 patients (58%) who did not was 70% (47-87) vs 72% (53-86), respectively. In patients with vs without prior alloSCT, the medians (95% CI) for DOR were 14.6 months (8.7-23.6) vs NR (4.7-NE), and the medians (95% CI) for OS were 25.4 months (14.2-NE) vs NR (9.0-NE), respectively. Grade ≥3 CRS occurred in 17% and 28% of patients with or without prior alloSCT, and Grade ≥3 neurologic events occurred in 26% and 25%, respectively.

For patients who achieved CR/CRi and did (n=10) or did not (n=29) proceed to subsequent alloSCT post–KTE-X19 infusion, the median (95%CI) DOR was NR (NE-NE) and 14.6 months (8.7-23.6), and the median (95% CI) OS was NR (7.6-NE) and 26.0 months (18.6-NE), respectively.

A pooled analysis of all Phase 1 and 2 patients treated at the pivotal dose (N=78) was newly conducted, with a median follow-up of 29.7 months (range, 20.7-58.3). The similar results observed in this expanded data set as shown in the Table further support the subgroup outcomes described above in Phase 2 patients.

Conclusion
Adults with R/R B-ALL benefitted from KTE-X19, with manageable safety, regardless of prior exposure to blinatumomab or prior alloSCT, though survival appeared better in patients without these prior therapies and in earlier lines of therapy, with limited patient numbers in some subgroups.

roups.

Keyword(s): Adult, B cell acute lymphoblastic leukemia, CAR-T

Presentation during EHA2022: All (e)Poster presentations will be made available as of Friday, June 10, 2022 (09:00 CEST) and will be accessible for on-demand viewing until Monday, August 15, 2022 on the Congress platform.

Abstract: P356

Type: Poster presentation

Session title: Acute lymphoblastic leukemia - Clinical

Background
Brexucabtagene autoleucel (KTE-X19) is approved in the US for the treatment of adult patients with R/R B-ALL based on the positive results of the ZUMA-3 study. In the pivotal Phase 2 portion of ZUMA-3, the overall complete remission (CR) rate (CR + CR with incomplete hematologic recovery [CRi]) was 71% (N=55; median follow-up 16.4 months; Shah et al. Lancet 2021).

Aims
To assess outcomes in ZUMA-3 by prior number of therapy lines, prior blinatumomab, prior allogeneic stem cell transplant (alloSCT), and subsequent alloSCT.

Methods
Eligible adults had R/R B-ALL and received a single infusion of KTE-X19 following leukapheresis and conditioning chemotherapy. Outcomes assessed by independent review are reported in all patients treated at the pivotal dose (1×106 CAR T cells/kg).

Results
As of 23 July 2021, the median follow-up among all treated patients in Phase 2 (N=55) was 26.8 months (range, 20.7-32.6). At baseline, 10 patients (18%) had 1 prior line of therapy, and 45 patients (82%) had ≥2 prior lines. The overall CR/CRi rates (95% CI) for patients with 1 or ≥2 prior lines of therapy were 90% (55-100) and 67% (51-80), respectively. In patients with 1 or ≥2 prior lines of therapy, the median (95% CI) duration of remission (DOR) was 4.7 months (1.8-not estimable [NE]) and 14.6 months (9.4-NE), and the median (95% CI) overall survival (OS) was not reached (NR) (2.1-NE) and 25.4 months (14.2-NE), respectively. Grade ≥3 cytokine release syndrome (CRS) occurred in 10% and 27% of patients with 1 or ≥2 prior lines of therapy, and Grade ≥3 neurologic events occurred in 30% and 24%, respectively.

Among the 25 patients (45%) who had prior blinatumomab at baseline, the overall CR/CRi rate (95% CI) was 60% (39-79), and 80% (61-92) in the 30 patients (55%) without prior blinatumomab. The median (95% CI) DOR was 19.1 months (1.3-NE) and 10.3 months (5.2-NE) in patients with or without prior blinatumomab, and the median (95% CI) OS was 14.2 months (3.2-26.0) and NR (18.6-NE), respectively. In patients with or without prior blinatumomab, rates of Grade ≥3 CRS were 24% and 23%, and rates of Grade ≥3 neurologic events were 20% and 30%, respectively.

The overall CR/CRi rate in the 23 patients (42%) who had prior alloSCT vs the 32 patients (58%) who did not was 70% (47-87) vs 72% (53-86), respectively. In patients with vs without prior alloSCT, the medians (95% CI) for DOR were 14.6 months (8.7-23.6) vs NR (4.7-NE), and the medians (95% CI) for OS were 25.4 months (14.2-NE) vs NR (9.0-NE), respectively. Grade ≥3 CRS occurred in 17% and 28% of patients with or without prior alloSCT, and Grade ≥3 neurologic events occurred in 26% and 25%, respectively.

For patients who achieved CR/CRi and did (n=10) or did not (n=29) proceed to subsequent alloSCT post–KTE-X19 infusion, the median (95%CI) DOR was NR (NE-NE) and 14.6 months (8.7-23.6), and the median (95% CI) OS was NR (7.6-NE) and 26.0 months (18.6-NE), respectively.

A pooled analysis of all Phase 1 and 2 patients treated at the pivotal dose (N=78) was newly conducted, with a median follow-up of 29.7 months (range, 20.7-58.3). The similar results observed in this expanded data set as shown in the Table further support the subgroup outcomes described above in Phase 2 patients.

Conclusion
Adults with R/R B-ALL benefitted from KTE-X19, with manageable safety, regardless of prior exposure to blinatumomab or prior alloSCT, though survival appeared better in patients without these prior therapies and in earlier lines of therapy, with limited patient numbers in some subgroups.

roups.

Keyword(s): Adult, B cell acute lymphoblastic leukemia, CAR-T

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