OUTCOMES IN ZUMA-5 WITH AXICABTAGENE CILOLEUCEL IN PATIENTS WITH RELAPSED/REFRACTORY INDOLENT NON-HODGKIN LYMPHOMA WHO HAD THE HIGH-RISK FEATURE OF EARLY PROGRESSION AFTER FIRST CHEMOIMMUNOTHERAPY
Author(s): ,
Caron A. Jacobson, MD
Affiliations:
Dana-Farber Cancer Institute,Boston, MA,United States
,
Julio C. Chavez, MD
Affiliations:
University of South Florida H. Lee Moffitt Cancer Center and Research Institute,Tampa, FL,United States
,
Alison R. Sehgal, MD
Affiliations:
UPMC Hillman Cancer Center,Pittsburgh, PA,United States
,
Basem M. William, MD
Affiliations:
The Ohio State University Comprehensive Cancer Center,Columbus, OH,United States
,
Javier Munoz, MD, MS, FACP
Affiliations:
Banner MD Anderson Cancer Center,Gilbert, AZ,United States
,
Gilles Salles, MD, PhD
Affiliations:
Memorial Sloan Kettering Cancer Center,New York City, NY,United States
,
Carla Casulo, MD
Affiliations:
University of Rochester Medical Center - James P. Wilmot Cancer Center,Rochester, NY,United States
,
Pashna N. Munshi, MD
Affiliations:
Georgetown Lombardi Comprehensive Cancer Center,Washington, DC,United States
,
David G. Maloney, MD, PhD
Affiliations:
Fred Hutchinson Cancer Research Center,Seattle, WA,United States
,
Sven de Vos, MD, PhD
Affiliations:
Ronald Reagan University of California Los Angeles Medical Center,Santa Monica, CA,United States
,
Ran Reshef, MD
Affiliations:
Columbia University Herbert Irving Comprehensive Cancer Center,New York City, NY,United States
,
Lori A. Leslie, MD
Affiliations:
John Theurer Cancer Center,Hackensack, NJ,United States
,
Ibrahim Yakoub-Agha, MD, PhD
Affiliations:
Centre Hospitalier Régional Universitaire de Lille,Lille,France
,
Olalekan O. Oluwole, MD, PHD, MBBS
Affiliations:
Vanderbilt University Medical Center,Nashville, TN,United States
,
Henry Chi Hang Fung, MD, FACP, FRCPE
Affiliations:
Fox Chase Cancer Center,Philadelphia, PA,United States
,
Vicki Plaks, LLB, PhD
Affiliations:
Kite, a Gilead Company,Santa Monica, CA,United States
,
Yin Yang, MS
Affiliations:
Kite, a Gilead Company,Santa Monica, CA,United States
,
Jennifer Lee
Affiliations:
Kite, a Gilead Company,Santa Monica, CA,United States
,
Mauro P. Avanzi, MD, PhD
Affiliations:
Kite, a Gilead Company,Santa Monica, CA,United States
Sattva S. Neelapu, MD
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston, TX,United States
EHA Library. Jacobson, MD C. 06/09/21; 324621; S213
Caron A. Jacobson, MD
Caron A. Jacobson, MD
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: S213

Type: Oral Presentation

Session title: Indolent & mantle cell lymphoma - Clinical

Background
Progression within 24 months from initiation of the first anti-CD20–containing chemoimmunotherapy (POD24) is an indicator of poor survival in indolent non-Hodgkin lymphoma (iNHL; Casulo & Barr. Blood. 2019). In the ZUMA-5 Phase 2 study of axicabtagene ciloleucel (axi-cel) anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed/refractory (R/R) iNHL, overall response rates (ORR) after a median of 17.5 months of follow-up were similarly high in those with and without POD24 (93% and 92%; Jacobson et al. ASH 2020. #700). 

Aims
To report updated outcomes with longer follow-up of axi-cel in patients in ZUMA-5 with R/R iNHL who had POD24.

Methods
Adults with R/R follicular lymphoma (FL) or marginal zone lymphoma (MZL) after ≥2 lines of therapy underwent leukapheresis followed by conditioning therapy and axi-cel infusion (2×106 CAR T cells/kg). Axi-cel–treated patients with available data on progression after an anti-CD20 monoclonal antibody + alkylating agent were included. The updated efficacy analysis occurred when ≥80 treated patients with FL had at least 18 months of follow-up.

Results
Of 129 patients at baseline, 81 patients (63%; 68 FL, 13 MZL) had POD24, and 48 patients (37%; 40 FL, 8 MZL) did not have POD24. Median prior lines of therapy in patients with and without POD24 were 3 and 3.5, respectively. High-risk characteristics of patients with and without POD24 included stage III/IV disease, 83% and 94%; ≥3 FLIPI, 44% and 43%; high tumor bulk (per GELF criteria), 51% and 44%; and refractory disease, 77% and 63%, respectively.

With a 23.3-month median follow-up, the ORR among efficacy-evaluable patients with POD24 (n=61) and without POD24 (n=37) was 92% each (complete response rates, 75% and 86%). At data cutoff, 52% of patients with POD24 and 70% without POD24 had ongoing responses. Median duration of response, progression-free survival, and overall survival were not reached in patients with and without POD24; 18-month estimated rates were 60% and 78%, 55% and 84%, and 85% and 94%, respectively.


Incidences of Grade ≥3 adverse events were similar in patients with and without POD24 (84% and 88%), including cytopenias (69% and 65%) and infections (15% and 21%). Grade ≥3 cytokine release syndrome (CRS) occurred in 9% and 2% of patients with and without POD24, respectively; Grade ≥3 neurologic events occurred in 17% of patients each. Median times to onset were similar in patients with and without POD24 for CRS (4 days each) and neurologic events (8 days and 7 days); median durations of CRS (7 days and 5 days) and neurologic events (11 days and 13 days) were also similar between groups.


In efficacy-evaluable patients with FL, median peak CAR T-cell levels were similar in patients with and without POD24 (35.8 cells/μL and 34.5 cells/μL). Peak levels of key inflammatory biomarkers and axi-cel product attributes were generally similar in patients with and without POD24.

Conclusion
Axi-cel showed a high rate of durable responses in patients with POD24 iNHL, a population with high-risk disease. Efficacy results, as well as safety and pharmacological profiles, appeared largely comparable between groups, with the exception of progression-free survival rates. 

Keyword(s): CAR-T, Follicular lymphoma, Marginal zone, Progression

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: S213

Type: Oral Presentation

Session title: Indolent & mantle cell lymphoma - Clinical

Background
Progression within 24 months from initiation of the first anti-CD20–containing chemoimmunotherapy (POD24) is an indicator of poor survival in indolent non-Hodgkin lymphoma (iNHL; Casulo & Barr. Blood. 2019). In the ZUMA-5 Phase 2 study of axicabtagene ciloleucel (axi-cel) anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed/refractory (R/R) iNHL, overall response rates (ORR) after a median of 17.5 months of follow-up were similarly high in those with and without POD24 (93% and 92%; Jacobson et al. ASH 2020. #700). 

Aims
To report updated outcomes with longer follow-up of axi-cel in patients in ZUMA-5 with R/R iNHL who had POD24.

Methods
Adults with R/R follicular lymphoma (FL) or marginal zone lymphoma (MZL) after ≥2 lines of therapy underwent leukapheresis followed by conditioning therapy and axi-cel infusion (2×106 CAR T cells/kg). Axi-cel–treated patients with available data on progression after an anti-CD20 monoclonal antibody + alkylating agent were included. The updated efficacy analysis occurred when ≥80 treated patients with FL had at least 18 months of follow-up.

Results
Of 129 patients at baseline, 81 patients (63%; 68 FL, 13 MZL) had POD24, and 48 patients (37%; 40 FL, 8 MZL) did not have POD24. Median prior lines of therapy in patients with and without POD24 were 3 and 3.5, respectively. High-risk characteristics of patients with and without POD24 included stage III/IV disease, 83% and 94%; ≥3 FLIPI, 44% and 43%; high tumor bulk (per GELF criteria), 51% and 44%; and refractory disease, 77% and 63%, respectively.

With a 23.3-month median follow-up, the ORR among efficacy-evaluable patients with POD24 (n=61) and without POD24 (n=37) was 92% each (complete response rates, 75% and 86%). At data cutoff, 52% of patients with POD24 and 70% without POD24 had ongoing responses. Median duration of response, progression-free survival, and overall survival were not reached in patients with and without POD24; 18-month estimated rates were 60% and 78%, 55% and 84%, and 85% and 94%, respectively.


Incidences of Grade ≥3 adverse events were similar in patients with and without POD24 (84% and 88%), including cytopenias (69% and 65%) and infections (15% and 21%). Grade ≥3 cytokine release syndrome (CRS) occurred in 9% and 2% of patients with and without POD24, respectively; Grade ≥3 neurologic events occurred in 17% of patients each. Median times to onset were similar in patients with and without POD24 for CRS (4 days each) and neurologic events (8 days and 7 days); median durations of CRS (7 days and 5 days) and neurologic events (11 days and 13 days) were also similar between groups.


In efficacy-evaluable patients with FL, median peak CAR T-cell levels were similar in patients with and without POD24 (35.8 cells/μL and 34.5 cells/μL). Peak levels of key inflammatory biomarkers and axi-cel product attributes were generally similar in patients with and without POD24.

Conclusion
Axi-cel showed a high rate of durable responses in patients with POD24 iNHL, a population with high-risk disease. Efficacy results, as well as safety and pharmacological profiles, appeared largely comparable between groups, with the exception of progression-free survival rates. 

Keyword(s): CAR-T, Follicular lymphoma, Marginal zone, Progression

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