Early changes in soluble intracellular adhesion molecule‐1 as prognostic biomarkers to immune checkpoint inhibitor

Author:

Ji Dongmei12,Jiang Shiyu23,Zhang Qunling23,Wang Y. Ken4,Zhang Jian25,Shen Weina25,Li Wenhua26,Liu Rujiao25,Wang Jessica7,Mavis Cory78,Gu Juan J.78,Hu Xichun29

Affiliation:

1. Department of Head and Neck Tumors and Neuroendocrine Tumors Fudan University Shanghai Cancer Center Shanghai China

2. Department of Oncology, Shanghai Medical College Fudan University Shanghai China

3. Department of Lymphoma Fudan University Shanghai Cancer Center Shanghai China

4. Division of Management and Education University of Pittsburgh Bradford Campus Bradford Pennsylvania USA

5. Phase I Clinical Trial Center Fudan University Shanghai Cancer Center Shanghai China

6. Department of Gastrointestinal Medical Oncology Fudan University Shanghai Cancer Center Shanghai China

7. Department of Medicine Roswell Park Comprehensive Cancer Center Buffalo New York USA

8. Department of Immunology Roswell Park Comprehensive Cancer Center Buffalo New York USA

9. Department of Breast cancer and Urological Medical Oncology Fudan University Shanghai Cancer Center Shanghai China

Abstract

AbstractSerologic biomarker to predict clinical outcome is needed for immune checkpoint inhibitors (ICIs). We evaluated soluble intercellular adhesion molecules‐1 (sICAM‐1) as a predictor of response to ICIs treatment. Ninety‐five patients with cancer treated with ICI were studied. The serum sICAM‐1 levels of baseline, post two cycle therapy and end of therapy (EOT) were measured by enzyme‐linked immunoassay. We randomly assigned the patients into the primary cohort (n = 47) and validation cohort (n = 48). Serum sICAM‐1 post two cycle (277.7 ± 181.6 ng/mL) and EOT (403.9 ± 218.9 ng/mL) were significantly elevated compared to baseline (244.8 ± 153.8 ng/mL, p = 0.008 and p = 0.004, respectively). Early changes of sICAM‐1 (ΔsICAM‐1), deemed as sICAM‐1 after two cycles minus baseline, were assessed. Following ICI treatments, responders had significantly lower ΔsICAM‐1 compared with nonresponders in the primary cohort (p = 0.040) and the validation cohort (p = 0.026). High ΔsICAM‐1 was strongly associated with inferior progression‐free survival (PFS; (primary cohort: p = 0.001 and validation cohort: p = 0.002) and overall survival (OS; (primary cohort: p < 0.001 and validation cohort: p = 0.007). The ΔsICAM‐1 remained independently associated with worse PFS and OS in the primary cohort and the validation cohort. Subgroup analysis indicated patients whose sICAM‐1 significantly elevated had shorter PFS and OS in both anti‐PD‐1 and anti‐PD‐L1 treatment groups. Early change of serum sICAM‐1 could be used to monitor and predict clinical benefit of ICI therapy in patients with solid cancer.

Publisher

Wiley

Subject

General Pharmacology, Toxicology and Pharmaceutics,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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