Clinical, Tumor, and Product Features Associated With Outcomes After Axicabtagene Ciloleucel Therapy in Follicular Lymphoma

Authors

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

Publication Date

8-15-2025

Journal

Journal of Clinical Investigation

DOI

10.1172/JCI181893

PMID

40536814

PMCID

PMC12352890

PubMedCentral® Posted Date

8-15-2025

PubMedCentral® Full Text Version

Post-print

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 patients with follicular lymphoma (FL).

Results: In univariate and multivariate analyses, pretreatment inflammatory markers, including TNF-α and IL-12p40, as well as total metabolic tumor volume (TMTV), associated with disease progression. Conversely, T-naive–like product phenotype associated with improved outcome, particularly in patients with high TMTV. These covariates improved risk stratification when combined with the FL International Prognostic Index. Postinfusion, CAR T cell expansion associated with improved outcome, while serum inflammatory and immunomodulatory markers, including TNF-α, 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 posttreatment 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.

Keywords

Adult, Aged, Female, Humans, Male, Middle Aged, Antigens, CD19, Immunotherapy, Adoptive, Lymphoma, Follicular, Biological Products, Hematology, Oncology, Cytokines, Lymphomas, T cells

Comments

Trial Registration: ClinicalTrials.gov NCT03105336.

Funding: Kite, a Gilead Company.

Published Open-Access

yes

Recommended Citation

Poddar, Soumya; Yan, Jiali; Tiwari, Gayatri; et al., "Clinical, Tumor, and Product Features Associated With Outcomes After Axicabtagene Ciloleucel Therapy in Follicular Lymphoma" (2025). Faculty, Staff and Student Publications. 4899.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4899