Peripheral eosinophil counts predict efficacy of anti-CD19 CAR-T cell therapy against B-lineage non-Hodgkin lymphoma.

Journal Article (Journal Article)

Rationale: The onset of cytokine release syndrome (CRS) and in vivo persistence of anti-CD19 chimeric antigen receptor T (CAR-T) cells after infusion correlate with clinical responsiveness. However, there are no known baseline biomarkers that can predict the prognosis of patients with B-lineage non-Hodgkin lymphoma (B-NHL). The aim of this study was to identify blood cell populations associated with beneficial outcomes in B-NHL patients administered CAR-T cell immunotherapies. Methods: We enumerated peripheral blood and CAR-T cells by retrospectively analyzing three CAR-T cell trials involving 65 B-NHL patients. We used a preclinical model to elucidate the eosinophil mechanism in CAR-T cell therapy. Results: During an observation period up to 30 mo, B-NHL patients with higher baseline eosinophil counts had higher objective response rates than those with low eosinophil counts. Higher baseline eosinophil counts were also significantly associated with durable progression-free survival (PFS). The predictive significance of baseline eosinophil counts was validated in two independent cohorts. A preclinical model showed that eosinophil depletion impairs the intratumoral infiltration of transferred CAR-T cells and reduces CAR-T cell antitumor efficacy. Conclusion: The results of this study suggest that peripheral eosinophils could serve as stratification biomarkers and a recruitment machinery to facilitate anti-CD19 CAR-T cell therapy in B-NHL patients.

Full Text

Duke Authors

Cited Authors

  • Jia, Q; Qin, D; He, F; Xie, Q; Ying, Z; Zhang, Y; Song, Y; Cheng, J-N; Zuo, X; Xu, L; Fang, H; Hu, C; Peng, L; Jin, T; Shi, Z; Alexander, PB; Wang, Y; Liu, Y; Han, W; Zhu, J; Wang, P; Li, Q-J; Zhu, B

Published Date

  • 2021

Published In

Volume / Issue

  • 11 / 10

Start / End Page

  • 4699 - 4709

PubMed ID

  • 33754022

Pubmed Central ID

  • PMC7978305

Electronic International Standard Serial Number (EISSN)

  • 1838-7640

Digital Object Identifier (DOI)

  • 10.7150/thno.54546

Language

  • eng

Conference Location

  • Australia