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CLINICAL AND PATIENT-REPORTED OUTCOMES IN A PHASE 3 STUDY OF AXICABTAGENE CILOLEUCEL (AXI-CEL) VS STANDARD-OF-CARE IN ELDERLY PATIENTS WITH RELAPSED/REFRACTORY LARGE B-CELL LYMPHOMA (ZUMA-7)
Author(s): ,
Anna Sureda
Affiliations:
Hematology Department,Institut Català d'Oncologia-Hospitalet, IDIBELL, Universitat de Barcelona,Barcelona,Espagne;Hematology Department,Institut Català d'Oncologia-Hospitalet, IDIBELL, Universitat de Barcelona,Barcelona,Spanien;Hematology Department,Institut Català d'Oncologia-Hospitalet, IDIBELL, Universitat de Barcelona,Barcelona,Spagna;Hematology Department,Institut Català d'Oncologia-Hospitale
,
Jason Westin
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,États-unis;The University of Texas MD Anderson Cancer Center,Houston,Vereinigte Staaten;The University of Texas MD Anderson Cancer Center,Houston,Stati Uniti;The University of Texas MD Anderson Cancer Center,Houston,United States;The University of Texas MD Anderson Cancer Center,Houston,Estados Unidos;The University of Texas MD Anderson Can
,
Frederick L. Locke
Affiliations:
Moffitt Cancer Center,Tampa,États-unis;Moffitt Cancer Center,Tampa,Vereinigte Staaten;Moffitt Cancer Center,Tampa,Stati Uniti;Moffitt Cancer Center,Tampa,United States;Moffitt Cancer Center,Tampa,Estados Unidos;Moffitt Cancer Center,Tampa,Verenigde Staten;Moffitt Cancer Center,Tampa,Estados Unidos;Moffitt Cancer Center,Tampa,United States;Moffitt Cancer Center,Tampa,USA
,
Michael Dickinson
Affiliations:
Peter MacCallum Cancer Centre, Royal Melbourne Hospital and the University of Melbourne,Melbourne, Victoria,Australie;Peter MacCallum Cancer Centre, Royal Melbourne Hospital and the University of Melbourne,Melbourne, Victoria,Australien;Peter MacCallum Cancer Centre, Royal Melbourne Hospital and the University of Melbourne,Melbourne, Victoria,Australia;Peter MacCallum Cancer Centre, Royal Melbourn
,
Armin Ghobadi
Affiliations:
Washington University School of Medicine,St Louis,États-unis;Washington University School of Medicine,St Louis,Vereinigte Staaten;Washington University School of Medicine,St Louis,Stati Uniti;Washington University School of Medicine,St Louis,United States;Washington University School of Medicine,St Louis,Estados Unidos;Washington University School of Medicine,St Louis,Verenigde Staten;Washington U
,
Mahmoud Elsawy
Affiliations:
Division of Hematology, Department of Medicine,Dalhousie University,Halifax, Nova Scotia,Canada;Division of Hematology, Department of Medicine,Dalhousie University,Halifax, Nova Scotia,Kanada;Division of Hematology, Department of Medicine,Dalhousie University,Halifax, Nova Scotia,Canada;Division of Hematology, Department of Medicine,Dalhousie University,Halifax, Nova Scotia,Canada;Division of Hema
,
Tom van Meerten
Affiliations:
University Medical Center Groningen, on behalf of HOVON/LLPC,Groningen,Pays-bas;University Medical Center Groningen, on behalf of HOVON/LLPC,Groningen,Niederlande;University Medical Center Groningen, on behalf of HOVON/LLPC,Groningen,Paesi Bassi;University Medical Center Groningen, on behalf of HOVON/LLPC,Groningen,Netherland;University Medical Center Groningen, on behalf of HOVON/LLPC,Groningen,P
,
David B. Miklos
Affiliations:
Stanford University School of Medicine, Stanford,États-unis;Stanford University School of Medicine, Stanford,Vereinigte Staaten;Stanford University School of Medicine, Stanford,Stati Uniti;Stanford University School of Medicine, Stanford,United States;Stanford University School of Medicine, Stanford,Estados Unidos;Stanford University School of Medicine, Stanford,Verenigde Staten;Stanford Universit
,
Matthew Ulrickson
Affiliations:
Banner MD Anderson Cancer Center,Gilbert,États-unis;Banner MD Anderson Cancer Center,Gilbert,Vereinigte Staaten;Banner MD Anderson Cancer Center,Gilbert,Stati Uniti;Banner MD Anderson Cancer Center,Gilbert,United States;Banner MD Anderson Cancer Center,Gilbert,Estados Unidos;Banner MD Anderson Cancer Center,Gilbert,Verenigde Staten;Banner MD Anderson Cancer Center,Gilbert,Estados Unidos;Banner MD
,
Miguel-Angel Perales
Affiliations:
Memorial Sloan-Kettering Cancer Center,New York,États-unis;Memorial Sloan-Kettering Cancer Center,New York,Vereinigte Staaten;Memorial Sloan-Kettering Cancer Center,New York,Stati Uniti;Memorial Sloan-Kettering Cancer Center,New York,United States;Memorial Sloan-Kettering Cancer Center,New York,Estados Unidos;Memorial Sloan-Kettering Cancer Center,New York,Verenigde Staten;Memorial Sloan-Kettering
,
Umar Farooq
Affiliations:
University of Iowa,Iowa City,États-unis;University of Iowa,Iowa City,Vereinigte Staaten;University of Iowa,Iowa City,Stati Uniti;University of Iowa,Iowa City,United States;University of Iowa,Iowa City,Estados Unidos;University of Iowa,Iowa City,Verenigde Staten;University of Iowa,Iowa City,Estados Unidos;University of Iowa,Iowa City,United States;University of Iowa,Iowa City,USA
,
Luciano Wannesson
Affiliations:
Istituto Oncologico della Svizzera Italiana,Bellinzona,Suisse;Istituto Oncologico della Svizzera Italiana,Bellinzona,Schweiz;Istituto Oncologico della Svizzera Italiana,Bellinzona,Svizzera;Istituto Oncologico della Svizzera Italiana,Bellinzona,Switzerland;Istituto Oncologico della Svizzera Italiana,Bellinzona,Suiza;Istituto Oncologico della Svizzera Italiana,Bellinzona,Zwitserland;Istituto Oncolog
,
Lori Leslie
Affiliations:
John Theurer Cancer Center,Hackensack,États-unis;John Theurer Cancer Center,Hackensack,Vereinigte Staaten;John Theurer Cancer Center,Hackensack,Stati Uniti;John Theurer Cancer Center,Hackensack,United States;John Theurer Cancer Center,Hackensack,Estados Unidos;John Theurer Cancer Center,Hackensack,Verenigde Staten;John Theurer Cancer Center,Hackensack,Estados Unidos;John Theurer Cancer Center,Hack
,
Marie José Kersten
Affiliations:
Amsterdam UMC, University of Amsterdam, on behalf of HOVON/LLPC, Amsterdam,Pays-bas;Amsterdam UMC, University of Amsterdam, on behalf of HOVON/LLPC, Amsterdam,Niederlande;Amsterdam UMC, University of Amsterdam, on behalf of HOVON/LLPC, Amsterdam,Paesi Bassi;Amsterdam UMC, University of Amsterdam, on behalf of HOVON/LLPC, Amsterdam,Netherland;Amsterdam UMC, University of Amsterdam, on behalf of HOV
,
Caron A. Jacobson
Affiliations:
Dana-Farber Cancer Institute,Boston,États-unis;Dana-Farber Cancer Institute,Boston,Vereinigte Staaten;Dana-Farber Cancer Institute,Boston,Stati Uniti;Dana-Farber Cancer Institute,Boston,United States;Dana-Farber Cancer Institute,Boston,Estados Unidos;Dana-Farber Cancer Institute,Boston,Verenigde Staten;Dana-Farber Cancer Institute,Boston,Estados Unidos;Dana-Farber Cancer Institute,Boston,United St
,
John M. Pagel
Affiliations:
Swedish Cancer Institute,Seattle,États-unis;Swedish Cancer Institute,Seattle,Vereinigte Staaten;Swedish Cancer Institute,Seattle,Stati Uniti;Swedish Cancer Institute,Seattle,United States;Swedish Cancer Institute,Seattle,Estados Unidos;Swedish Cancer Institute,Seattle,Verenigde Staten;Swedish Cancer Institute,Seattle,Estados Unidos;Swedish Cancer Institute,Seattle,United States;Swedish Cancer Inst
,
Gerald Wulf
Affiliations:
University Medicine Göttingen,Göttingen,Allemagne;University Medicine Göttingen,Göttingen,Deutschland;University Medicine Göttingen,Göttingen,Germania;University Medicine Göttingen,Göttingen,Germany;University Medicine Göttingen,Göttingen,Alemania;University Medicine Göttingen,Göttingen,Duitsland;University Medicine Göttingen,Göttingen,Alemanha;University Medicine Göttingen,Göttingen,Германия;Univ
,
Patrick Johnston
Affiliations:
Mayo Clinic,Rochester,États-unis;Mayo Clinic,Rochester,Vereinigte Staaten;Mayo Clinic,Rochester,Stati Uniti;Mayo Clinic,Rochester,United States;Mayo Clinic,Rochester,Estados Unidos;Mayo Clinic,Rochester,Verenigde Staten;Mayo Clinic,Rochester,Estados Unidos;Mayo Clinic,Rochester,United States;Mayo Clinic,Rochester,USA
,
Aaron P. Rapoport
Affiliations:
University of Maryland School of Medicine and Marlene and Stewart Greenebaum Comprehensive Cancer Center,Baltimore,États-unis;University of Maryland School of Medicine and Marlene and Stewart Greenebaum Comprehensive Cancer Center,Baltimore,Vereinigte Staaten;University of Maryland School of Medicine and Marlene and Stewart Greenebaum Comprehensive Cancer Center,Baltimore,Stati Uniti;University of
,
Leo I. Gordon
Affiliations:
Northwestern University Feinberg School of Medicine,Chicago,États-unis;Northwestern University Feinberg School of Medicine,Chicago,Vereinigte Staaten;Northwestern University Feinberg School of Medicine,Chicago,Stati Uniti;Northwestern University Feinberg School of Medicine,Chicago,United States;Northwestern University Feinberg School of Medicine,Chicago,Estados Unidos;Northwestern University Feinb
,
Yin Yang
Affiliations:
Kite, a Gilead Company,Santa Monica,États-unis;Kite, a Gilead Company,Santa Monica,Vereinigte Staaten;Kite, a Gilead Company,Santa Monica,Stati Uniti;Kite, a Gilead Company,Santa Monica,United States;Kite, a Gilead Company,Santa Monica,Estados Unidos;Kite, a Gilead Company,Santa Monica,Verenigde Staten;Kite, a Gilead Company,Santa Monica,Estados Unidos;Kite, a Gilead Company,Santa Monica,United St
,
Andrew Peng
Affiliations:
Kite, a Gilead Company,Santa Monica,États-unis;Kite, a Gilead Company,Santa Monica,Vereinigte Staaten;Kite, a Gilead Company,Santa Monica,Stati Uniti;Kite, a Gilead Company,Santa Monica,United States;Kite, a Gilead Company,Santa Monica,Estados Unidos;Kite, a Gilead Company,Santa Monica,Verenigde Staten;Kite, a Gilead Company,Santa Monica,Estados Unidos;Kite, a Gilead Company,Santa Monica,United St
,
Linqiu Du
Affiliations:
Kite, A Gilead Company,Santa Monica ,États-unis;Kite, A Gilead Company,Santa Monica ,Vereinigte Staaten;Kite, A Gilead Company,Santa Monica ,Stati Uniti;Kite, A Gilead Company,Santa Monica ,United States;Kite, A Gilead Company,Santa Monica ,Estados Unidos;Kite, A Gilead Company,Santa Monica ,Verenigde Staten;Kite, A Gilead Company,Santa Monica ,Estados Unidos;Kite, A Gilead Company,Santa Monica ,U
,
Julia T. Snider
Affiliations:
Kite, a Gilead Company,Santa Monica,États-unis;Kite, a Gilead Company,Santa Monica,Vereinigte Staaten;Kite, a Gilead Company,Santa Monica,Stati Uniti;Kite, a Gilead Company,Santa Monica,United States;Kite, a Gilead Company,Santa Monica,Estados Unidos;Kite, a Gilead Company,Santa Monica,Verenigde Staten;Kite, a Gilead Company,Santa Monica,Estados Unidos;Kite, a Gilead Company,Santa Monica,United St
,
Jina Shah
Affiliations:
Kite, a Gilead Company,Santa Monica,États-unis;Kite, a Gilead Company,Santa Monica,Vereinigte Staaten;Kite, a Gilead Company,Santa Monica,Stati Uniti;Kite, a Gilead Company,Santa Monica,United States;Kite, a Gilead Company,Santa Monica,Estados Unidos;Kite, a Gilead Company,Santa Monica,Verenigde Staten;Kite, a Gilead Company,Santa Monica,Estados Unidos;Kite, a Gilead Company,Santa Monica,United St
,
Marco Schupp
Affiliations:
Kite, a Gilead Company,Santa Monica,États-unis;Kite, a Gilead Company,Santa Monica,Vereinigte Staaten;Kite, a Gilead Company,Santa Monica,Stati Uniti;Kite, a Gilead Company,Santa Monica,United States;Kite, a Gilead Company,Santa Monica,Estados Unidos;Kite, a Gilead Company,Santa Monica,Verenigde Staten;Kite, a Gilead Company,Santa Monica,Estados Unidos;Kite, a Gilead Company,Santa Monica,United St
,
Paul Cheng
Affiliations:
Kite, a Gilead Company,Santa Monica,États-unis;Kite, a Gilead Company,Santa Monica,Vereinigte Staaten;Kite, a Gilead Company,Santa Monica,Stati Uniti;Kite, a Gilead Company,Santa Monica,United States;Kite, a Gilead Company,Santa Monica,Estados Unidos;Kite, a Gilead Company,Santa Monica,Verenigde Staten;Kite, a Gilead Company,Santa Monica,Estados Unidos;Kite, a Gilead Company,Santa Monica,United St
,
Christina To
Affiliations:
Kite, a Gilead Company,Santa Monica,États-unis;Kite, a Gilead Company,Santa Monica,Vereinigte Staaten;Kite, a Gilead Company,Santa Monica,Stati Uniti;Kite, a Gilead Company,Santa Monica,United States;Kite, a Gilead Company,Santa Monica,Estados Unidos;Kite, a Gilead Company,Santa Monica,Verenigde Staten;Kite, a Gilead Company,Santa Monica,Estados Unidos;Kite, a Gilead Company,Santa Monica,United St
Olalekan O. Oluwole
Affiliations:
Vanderbilt University Cancer Center,Nashville,États-unis;Vanderbilt University Cancer Center,Nashville,Vereinigte Staaten;Vanderbilt University Cancer Center,Nashville,Stati Uniti;Vanderbilt University Cancer Center,Nashville,United States;Vanderbilt University Cancer Center,Nashville,Estados Unidos;Vanderbilt University Cancer Center,Nashville,Verenigde Staten;Vanderbilt University Cancer Center,
(Abstract release date: 05/26/22) EHA Library. Sureda A. 06/11/22; 357075; S211
Dr. Anna Sureda
Dr. Anna Sureda
Contributions
Abstract
Presentation during EHA2022: All Oral presentations will be presented between Friday, June 10 and Sunday, June 12 and will be accessible for on-demand viewing from Monday, June 20 until Monday, August 15, 2022 on the Congress platform.

Abstract: S211

Type: Oral Presentation

Session title: Aggressive Lymphoma - CART

Background
The median age at large B-cell lymphoma (LBCL) diagnosis is 66 years, and older patients with relapsed/refractory (R/R) LBCL are at risk of inferior outcomes, increased toxicity, and inability to tolerate second-line standard-of-care (SOC) treatment (Di M, et al. Oncologist. 2021). Further, second-line SOC treatment is often associated with poor health-related quality of life (Lin V, et al. J Clin Oncol. 2020;38:e20070). In the global Phase 3, randomized ZUMA-7 study, axi-cel, an autologous antiCD19 CAR T-cell therapy, significantly improved event-free survival (EFS; hazard ratio [HR], 0.398, P<0.0001; median 8.3 vs 2 months, respectively) compared with second-line SOC in R/R LBCL (Locke FL, et al. N Engl J Med. 2022;386:640-654). 

Aims
Here we report results of a planned subgroup analysis of the ZUMA-7 study assessing outcomes, including patient-reported outcomes (PROs), of second-line axi-cel vs SOC in patients aged ≥65 years. 

Methods

Patients with ECOG performance status 0-1 and R/R LBCL ≤12 months after first-line chemoimmunotherapy were randomized 1:1 to axi-cel or SOC (2-3 cycles of platinum-based chemoimmunotherapy; patients with partial or complete response [CR] proceeded to high-dose therapy with autologous stem cell transplantation). PRO instruments, including the EORTC QLQ-C30 (Global Health and Physical Functioning) and the EQ-5D-5L visual analog scale (VAS), were administered at baseline (prior to treatment), Day 50, Day 100, Day 150, and Month 9, then every 3 months up to 24 months or time of EFS event, whichever occurred first. The quality-of-life analysis set included all patients who had a baseline PRO and ≥1 completed measure at Day 50, 100, or 150. A clinically meaningful change was defined as 10 points for each EORTC QLQ-C30 score and 7 points for EQ-5D-5L VAS score. 

Results
The data cutoff for this analysis was March 18, 2021 and included 51 axi-cel and 58 SOC patients with median ages of 70 years (range, 65-80) and 69 years (range, 65-81), respectively. At baseline, more axi-cel vs SOC patients had high-risk features, including second-line age-adjusted International Prognostic Index 2-3 (53% vs 31%) and elevated lactate dehydrogenase (61% vs 41%). EFS was superior with axi-cel vs SOC (HR, 0.276, P<0.0001), with higher CR rates (75% vs 33%). Grade ≥3 treatment-emergent adverse events (AEs) occurred in 94% and 82% of axi-cel and SOC patients, respectively, and Grade 5 treatment-related AEs occurred in 0 and 1 patient. In the quality-of-life analysis set comprising 46 axi-cel and 42 SOC patients, there were statistically significant and clinically meaningful differences in mean change of scores from baseline at Day 100 favoring axi-cel for EORTC QLQ-C30 Global Health (P<0.0001) and Physical Functioning (P=0.0019) and EQ-5D-5L VAS (P<0.0001). For all 3 domains, scores also favored (P<0.05) axi-cel over SOC at Day 150. The mean estimated scores numerically returned to or exceeded baseline scores earlier in the axi-cel arm (by Day 150) but never equaled or exceeded baseline scores by Month 15 in the SOC arm. 

Conclusion
Axi-cel demonstrated superiority over second-line SOC in patients ≥65 years with significantly improved EFS and a manageable safety profile. Axi-cel also showed meaningful improvement in quality of life over SOC, measured by multiple validated PRO instruments, with suggested faster recovery to pretreatment quality of life. The superior clinical outcomes and patient experience with axi-cel over SOC should help inform treatment choices in second-line R/R LBCL for patients ≥65 years. 

Keyword(s): B cell lymphoma, CAR-T, Patient reported outcomes



© 2022 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2022 ASCO Annual Meeting. All rights reserved.
Presentation during EHA2022: All Oral presentations will be presented between Friday, June 10 and Sunday, June 12 and will be accessible for on-demand viewing from Monday, June 20 until Monday, August 15, 2022 on the Congress platform.

Abstract: S211

Type: Oral Presentation

Session title: Aggressive Lymphoma - CART

Background
The median age at large B-cell lymphoma (LBCL) diagnosis is 66 years, and older patients with relapsed/refractory (R/R) LBCL are at risk of inferior outcomes, increased toxicity, and inability to tolerate second-line standard-of-care (SOC) treatment (Di M, et al. Oncologist. 2021). Further, second-line SOC treatment is often associated with poor health-related quality of life (Lin V, et al. J Clin Oncol. 2020;38:e20070). In the global Phase 3, randomized ZUMA-7 study, axi-cel, an autologous antiCD19 CAR T-cell therapy, significantly improved event-free survival (EFS; hazard ratio [HR], 0.398, P<0.0001; median 8.3 vs 2 months, respectively) compared with second-line SOC in R/R LBCL (Locke FL, et al. N Engl J Med. 2022;386:640-654). 

Aims
Here we report results of a planned subgroup analysis of the ZUMA-7 study assessing outcomes, including patient-reported outcomes (PROs), of second-line axi-cel vs SOC in patients aged ≥65 years. 

Methods

Patients with ECOG performance status 0-1 and R/R LBCL ≤12 months after first-line chemoimmunotherapy were randomized 1:1 to axi-cel or SOC (2-3 cycles of platinum-based chemoimmunotherapy; patients with partial or complete response [CR] proceeded to high-dose therapy with autologous stem cell transplantation). PRO instruments, including the EORTC QLQ-C30 (Global Health and Physical Functioning) and the EQ-5D-5L visual analog scale (VAS), were administered at baseline (prior to treatment), Day 50, Day 100, Day 150, and Month 9, then every 3 months up to 24 months or time of EFS event, whichever occurred first. The quality-of-life analysis set included all patients who had a baseline PRO and ≥1 completed measure at Day 50, 100, or 150. A clinically meaningful change was defined as 10 points for each EORTC QLQ-C30 score and 7 points for EQ-5D-5L VAS score. 

Results
The data cutoff for this analysis was March 18, 2021 and included 51 axi-cel and 58 SOC patients with median ages of 70 years (range, 65-80) and 69 years (range, 65-81), respectively. At baseline, more axi-cel vs SOC patients had high-risk features, including second-line age-adjusted International Prognostic Index 2-3 (53% vs 31%) and elevated lactate dehydrogenase (61% vs 41%). EFS was superior with axi-cel vs SOC (HR, 0.276, P<0.0001), with higher CR rates (75% vs 33%). Grade ≥3 treatment-emergent adverse events (AEs) occurred in 94% and 82% of axi-cel and SOC patients, respectively, and Grade 5 treatment-related AEs occurred in 0 and 1 patient. In the quality-of-life analysis set comprising 46 axi-cel and 42 SOC patients, there were statistically significant and clinically meaningful differences in mean change of scores from baseline at Day 100 favoring axi-cel for EORTC QLQ-C30 Global Health (P<0.0001) and Physical Functioning (P=0.0019) and EQ-5D-5L VAS (P<0.0001). For all 3 domains, scores also favored (P<0.05) axi-cel over SOC at Day 150. The mean estimated scores numerically returned to or exceeded baseline scores earlier in the axi-cel arm (by Day 150) but never equaled or exceeded baseline scores by Month 15 in the SOC arm. 

Conclusion
Axi-cel demonstrated superiority over second-line SOC in patients ≥65 years with significantly improved EFS and a manageable safety profile. Axi-cel also showed meaningful improvement in quality of life over SOC, measured by multiple validated PRO instruments, with suggested faster recovery to pretreatment quality of life. The superior clinical outcomes and patient experience with axi-cel over SOC should help inform treatment choices in second-line R/R LBCL for patients ≥65 years. 

Keyword(s): B cell lymphoma, CAR-T, Patient reported outcomes



© 2022 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2022 ASCO Annual Meeting. All rights reserved.

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