INTERIM ANALYSIS OF ZUMA-5: A PHASE 2 STUDY OF AXICABTAGENE CILOLEUCEL (AXI-CEL) IN PATIENTS WITH RELAPSED/REFRACTORY INDOLENT NON-HODGKIN LYMPHOMA
Author(s): ,
Caron A. Jacobson
Affiliations:
Dana-Farber Cancer Institute,Boston,United States
,
Julio C. Chavez
Affiliations:
University of South Florida H. Lee Moffitt Cancer Center and Research Institute,Tampa,United States
,
Alison R. Sehgal
Affiliations:
UPMC Hillman Cancer Center,Pittsburgh,United States
,
Basem M. William
Affiliations:
The Ohio State University Comprehensive Cancer Center,Columbus,United States
,
Javier Munoz
Affiliations:
Banner MD Anderson Cancer Center,Gilbert,United States
,
Gilles Salles
Affiliations:
Centre Hospitalier Lyon Sud,Pierre-Bénite,France
,
Carla Casulo
Affiliations:
University of Rochester Medical Center - James P. Wilmot Cancer Center,Rochester,United States
,
Pashna N. Munshi
Affiliations:
Georgetown Lombardi Comprehensive Cancer Center,Washington, D.C.,United States
,
David G. Maloney
Affiliations:
Fred Hutchinson Cancer Research Center,Seattle,United States
,
Sven de Vos
Affiliations:
Ronald Reagan University of California Los Angeles Medical Center, Santa Monica,United States
,
Ran Reshef
Affiliations:
Columbia University Herbert Irving Comprehensive Cancer Center,New York,United States
,
Lori A. Leslie
Affiliations:
John Theurer Cancer Center,Hackensack,United States
,
Ibrahim Yakoub-Agha
Affiliations:
Centre Hospitalier Régional Universitaire de Lille,Lille,France
,
Olalekan O. Oluwole
Affiliations:
Vanderbilt University Medical Center,Nashville,United States
,
Henry Chi Hang Fung
Affiliations:
Fox Chase Cancer Center,Philadelphia,United States
,
Vicki Plaks
Affiliations:
Kite, A Gilead Company,Santa Monica,United States
,
Yin Yang
Affiliations:
Kite, A Gilead Company,Santa Monica,United States
,
Jennifer Lee
Affiliations:
Kite, A Gilead Company,Santa Monica,United States
,
Mauro P. Avanzi
Affiliations:
Kite, A Gilead Company,Santa Monica,United States
Sattva S. Neelapu
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
EHA Library. A. Jacobson C. 06/12/20; 295106; S287
Caron A. Jacobson
Caron A. Jacobson
Contributions
Abstract

Abstract: S287

Type: Oral Presentation

Presentation during EHA25: All oral abstract presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Session title: CART cells

Background
Advanced-stage indolent non-Hodgkin Lymphoma (iNHL), including follicular lymphoma (FL) and marginal zone lymphoma (MZL), is considered incurable as most patients experience multiple relapses (Wang TP, et al. Ther Adv Hematol. 2017), highlighting a need for novel therapies.

Aims
To report interim results from ZUMA-5, a Phase 2, multicenter study of axi-cel, an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy, in patients with relapsed/refractory (R/R) iNHL.

Methods
Adult patients with R/R FL (Grades 1 – 3a) or MZL (nodal or extranodal) after ≥ 2 lines of therapy (including an anti-CD20 monoclonal antibody with an alkylating agent), and an ECOG PS of 0 – 1 were eligible. Patients were leukapheresed and received conditioning chemotherapy followed by axi-cel infusion at 2 × 106 CAR T cells/kg. The primary endpoint was objective response rate (ORR) by central review (Cheson, et al. J Clin Oncol. 2014). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety, and blood levels of cytokines and CAR T cells.

Results

As of August 20, 2019, 94 patients (80 with FL; 14 with MZL) received axi-cel with a median follow-up of 11.5 months (range, 4.2 – 24.9 months). The median age was 63 years (range, 34 – 79 years); 47% of patients were male; 52% had stage IV disease; 51% had FLIPI ≥ 3, and 59% had high tumor bulk (GELF). Patients had a median of 3 prior lines of therapy; 66% progressed < 2 years after initial anti-CD20 monoclonal antibody-containing therapy (POD24), and 73% were refractory to the last prior treatment.

Of 87 patients evaluable for efficacy, the ORR was 94% (79% complete response [CR] rate). Patients with FL (n = 80) had an ORR of 95% (80% CR rate). Patients with MZL (n = 7) had an ORR of 86% (71% CR rate). Overall, 68% of patients had ongoing responses as of the data cutoff. Updated data, including DOR, PFS, and OS with longer follow-up, will be included in the presentation.

Of 94 patients evaluable for safety, 83% experienced Grade ≥ 3 adverse events (AEs), most commonly neutropenia (33%) and anemia (28%). Grade ≥ 3 cytokine release syndrome (CRS; per Lee, et al. Blood. 2014) and neurologic events (NEs; per CTCAE version 4.03) occurred in 11% and 19% of patients, respectively. Median times to onset of CRS and NEs were 4 days and 7 days, with median durations of 6 days and 14.5 days, respectively. There were 2 Grade 5 AEs: multisystem organ failure in the context of CRS (related to axi-cel) and aortic dissection (unrelated to axi-cel). Median peak and AUC0-28 CAR T cell levels were 44 cells/µL and 490 cells/µL × days, respectively.

Conclusion
Axi-cel demonstrated significant and durable clinical benefit, with high rates of ORR and CR, and a manageable safety profile in patients with R/R iNHL.

Session topic: 25. Gene therapy, cellular immunotherapy and vaccination - Clinical

Keyword(s): CAR-T, Non-Hodgkin's lymphoma

Abstract: S287

Type: Oral Presentation

Presentation during EHA25: All oral abstract presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Session title: CART cells

Background
Advanced-stage indolent non-Hodgkin Lymphoma (iNHL), including follicular lymphoma (FL) and marginal zone lymphoma (MZL), is considered incurable as most patients experience multiple relapses (Wang TP, et al. Ther Adv Hematol. 2017), highlighting a need for novel therapies.

Aims
To report interim results from ZUMA-5, a Phase 2, multicenter study of axi-cel, an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy, in patients with relapsed/refractory (R/R) iNHL.

Methods
Adult patients with R/R FL (Grades 1 – 3a) or MZL (nodal or extranodal) after ≥ 2 lines of therapy (including an anti-CD20 monoclonal antibody with an alkylating agent), and an ECOG PS of 0 – 1 were eligible. Patients were leukapheresed and received conditioning chemotherapy followed by axi-cel infusion at 2 × 106 CAR T cells/kg. The primary endpoint was objective response rate (ORR) by central review (Cheson, et al. J Clin Oncol. 2014). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety, and blood levels of cytokines and CAR T cells.

Results

As of August 20, 2019, 94 patients (80 with FL; 14 with MZL) received axi-cel with a median follow-up of 11.5 months (range, 4.2 – 24.9 months). The median age was 63 years (range, 34 – 79 years); 47% of patients were male; 52% had stage IV disease; 51% had FLIPI ≥ 3, and 59% had high tumor bulk (GELF). Patients had a median of 3 prior lines of therapy; 66% progressed < 2 years after initial anti-CD20 monoclonal antibody-containing therapy (POD24), and 73% were refractory to the last prior treatment.

Of 87 patients evaluable for efficacy, the ORR was 94% (79% complete response [CR] rate). Patients with FL (n = 80) had an ORR of 95% (80% CR rate). Patients with MZL (n = 7) had an ORR of 86% (71% CR rate). Overall, 68% of patients had ongoing responses as of the data cutoff. Updated data, including DOR, PFS, and OS with longer follow-up, will be included in the presentation.

Of 94 patients evaluable for safety, 83% experienced Grade ≥ 3 adverse events (AEs), most commonly neutropenia (33%) and anemia (28%). Grade ≥ 3 cytokine release syndrome (CRS; per Lee, et al. Blood. 2014) and neurologic events (NEs; per CTCAE version 4.03) occurred in 11% and 19% of patients, respectively. Median times to onset of CRS and NEs were 4 days and 7 days, with median durations of 6 days and 14.5 days, respectively. There were 2 Grade 5 AEs: multisystem organ failure in the context of CRS (related to axi-cel) and aortic dissection (unrelated to axi-cel). Median peak and AUC0-28 CAR T cell levels were 44 cells/µL and 490 cells/µL × days, respectively.

Conclusion
Axi-cel demonstrated significant and durable clinical benefit, with high rates of ORR and CR, and a manageable safety profile in patients with R/R iNHL.

Session topic: 25. Gene therapy, cellular immunotherapy and vaccination - Clinical

Keyword(s): CAR-T, Non-Hodgkin's lymphoma

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