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

  • Theranostics. 2021 Mar 4;11(10):4699-4709. doi: 10.7150/thno.54546.
Qingzhu Jia  1  2 ,  Diyuan Qin  3  4 ,  Feng He  1  5 ,  Qichao Xie  1  2  6 ,  Zhitao Ying  7 ,  Yajing Zhang  8 ,  Yuqin Song  7 ,  Jia-Nan Cheng  1  2 ,  Xuejiao Zuo  1  2 ,  Luxiang Xu  1  2 ,  Hongliang Fang  5 ,  Chunyan Hu  1  2 ,  Lina Peng  1  2 ,  Tao Jin  5 ,  Zixiao Shi  5 ,  Peter B Alexander  4 ,  Yongsheng Wang  3 ,  Yarong Liu  5 ,  Weidong Han  8 ,  Jun Zhu  7 ,  Pin Wang  9 ,  Qi-Jing Li  4 ,  Bo Zhu  1  2
Affiliations
  • 1. Department of Oncology, Xinqiao Hospital, Army Medical University, Chongqing 400037, China.
  • 2. Chongqing Key Laboratory of Immunotherapy, Chongqing 400037, China.
  • 3. Department of Thoracic Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu 610041, China.
  • 4. Department of Immunology, Duke University Medical Center, Durham, NC, USA.
  • 5. R&D Department, HRAIN Biotechnology Co. Ltd., Shanghai, China.
  • 6. Department of Oncology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China.
  • 7. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China.
  • 8. Department of Bio-therapeutic, The First Medical Center, Chinese PLA General Hospital, Beijing, China.
  • 9. Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA; Department of Pharmaceutical Sciences and Pharmacology, University of Southern California, 3710 McClintock Ave., RTH506, Los Angeles, CA 90089, USA.
PMID: 33754022 DOI: 10.7150/thno.54546
Abstract

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.

Keywords
B-NHL; CAR-T; biomarker; eosinophil; infiltration.
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