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Clinical Research and Public HealthIn-Press PreviewHematologyOncology Open Access | 10.1172/JCI181893

Clinical, tumor and product features associated with outcomes after axicabtagene ciloleucel therapy in follicular lymphoma

Soumya Poddar,1 Jiali Yan,1 Gayatri Tiwari,1 Darawan Rinchai,1 Justin Budka,1 Wangshu Zhang,1 Weixin Peng,1 Shruti Salunkhe,1 Madison Davis,1 Qinghua Song,1 Sara Beygi,1 Harry Miao,1 Mike Mattie,2 Rhine S. Shen,1 Caron A. Jacobson,3 Davide Bedognetti,1 Simone Filosto,1 and Sattva S. Neelapu4

1Kite, a Gilead Company, Santa Monica, United States of America

2Kite, a Gilead company, Santa Monica, United States of America

3Dana-Farber Cancer Institute, Boston, United States of America

4The University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Kite, a Gilead Company, Santa Monica, United States of America

2Kite, a Gilead company, Santa Monica, United States of America

3Dana-Farber Cancer Institute, Boston, United States of America

4The University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Kite, a Gilead Company, Santa Monica, United States of America

2Kite, a Gilead company, Santa Monica, United States of America

3Dana-Farber Cancer Institute, Boston, United States of America

4The University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Kite, a Gilead Company, Santa Monica, United States of America

2Kite, a Gilead company, Santa Monica, United States of America

3Dana-Farber Cancer Institute, Boston, United States of America

4The University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Kite, a Gilead Company, Santa Monica, United States of America

2Kite, a Gilead company, Santa Monica, United States of America

3Dana-Farber Cancer Institute, Boston, United States of America

4The University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Kite, a Gilead Company, Santa Monica, United States of America

2Kite, a Gilead company, Santa Monica, United States of America

3Dana-Farber Cancer Institute, Boston, United States of America

4The University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Kite, a Gilead Company, Santa Monica, United States of America

2Kite, a Gilead company, Santa Monica, United States of America

3Dana-Farber Cancer Institute, Boston, United States of America

4The University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Kite, a Gilead Company, Santa Monica, United States of America

2Kite, a Gilead company, Santa Monica, United States of America

3Dana-Farber Cancer Institute, Boston, United States of America

4The University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Kite, a Gilead Company, Santa Monica, United States of America

2Kite, a Gilead company, Santa Monica, United States of America

3Dana-Farber Cancer Institute, Boston, United States of America

4The University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Kite, a Gilead Company, Santa Monica, United States of America

2Kite, a Gilead company, Santa Monica, United States of America

3Dana-Farber Cancer Institute, Boston, United States of America

4The University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Kite, a Gilead Company, Santa Monica, United States of America

2Kite, a Gilead company, Santa Monica, United States of America

3Dana-Farber Cancer Institute, Boston, United States of America

4The University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Kite, a Gilead Company, Santa Monica, United States of America

2Kite, a Gilead company, Santa Monica, United States of America

3Dana-Farber Cancer Institute, Boston, United States of America

4The University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Kite, a Gilead Company, Santa Monica, United States of America

2Kite, a Gilead company, Santa Monica, United States of America

3Dana-Farber Cancer Institute, Boston, United States of America

4The University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Kite, a Gilead Company, Santa Monica, United States of America

2Kite, a Gilead company, Santa Monica, United States of America

3Dana-Farber Cancer Institute, Boston, United States of America

4The University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Kite, a Gilead Company, Santa Monica, United States of America

2Kite, a Gilead company, Santa Monica, United States of America

3Dana-Farber Cancer Institute, Boston, United States of America

4The University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Kite, a Gilead Company, Santa Monica, United States of America

2Kite, a Gilead company, Santa Monica, United States of America

3Dana-Farber Cancer Institute, Boston, United States of America

4The University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Kite, a Gilead Company, Santa Monica, United States of America

2Kite, a Gilead company, Santa Monica, United States of America

3Dana-Farber Cancer Institute, Boston, United States of America

4The University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Filosto, S. in: PubMed | Google Scholar

1Kite, a Gilead Company, Santa Monica, United States of America

2Kite, a Gilead company, Santa Monica, United States of America

3Dana-Farber Cancer Institute, Boston, United States of America

4The University of Texas MD Anderson Cancer Center, Houston, United States of America

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Published June 19, 2025 - More info

J Clin Invest. https://doi.org/10.1172/JCI181893.
Copyright © 2025, Poddar et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published June 19, 2025 - Version history
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Abstract

BACKGROUND. Axicabtagene ciloleucel (axi-cel), anti-CD19 chimeric antigen receptor (CAR) T-cell therapy demonstrated remarkable efficacy with manageable toxicity in relapsed/refractory indolent B-cell lymphomas in the ZUMA-5 trial.

METHODS. Here, we report associations of product attributes, serum biomarkers, clinical features, and tumor characteristics with outcome in 124 follicular lymphoma (FL) patients.

RESULTS. In univariate and multivariate analyses, pre-treatment inflammatory markers, including TNFα and IL12p40, as well as total metabolic tumor volume (TMTV) associated with disease progression. Conversely, T-naïve-like product phenotype associated with improved outcome, particularly in high TMTV patients. These covariates improved risk stratification when combined with the FL International Prognostic Index. Post-infusion, CAR T-cell expansion associated with improved outcome, while serum inflammatory and immuno-modulatory markers, including TNFα associated with disease progression and occurrence of high-grade cytokine release syndrome or neurologic events, presenting targets to improve the therapeutic index of axi-cel in FL. Tumor gene expression profiling revealed that both type I and II IFN signaling associated with disease progression and higher expression of T cell exhaustion markers, including TIM3 and LAG3. Pre- or post-treatment CD19 expression on tumor was not associated with outcome.

CONCLUSION. These findings offer insights into mechanisms of resistance and toxicity, risk stratification, and strategies for development of next generation CAR-T approaches.

TRIAL REGISTRATION. ClinicalTrials.gov NCT03105336.

FUNDING. Kite, a Gilead Company.  

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