46P - Immunoprofiling of Peripheral Blood Cells as a Potential Predictor of Immune-Related Toxicity of PD-1 Inhibitors

Background

Checkpoint inhibitors have revolutionized treatment outcomes of several types of cancer. However, their administration is associated with unpredictable immune-related adverse events (irAEs). The objective of this study is to assess the potential predictive value of immune cells in peripheral blood for anticipating irAEs.

Methods

We prospectively enrolled patients with metastatic cancer treated with PD-1 inhibitors (nivolumab or pembrolizumab). Patients were recruited between 2017 and 2021 at the Masaryk Memorial Cancer Institute (Czech Republic). Before starting immunotherapy we performed immunoprofiling of key regulators and effectors of the immune system from peripheral blood cells using flow cytometry. We compared differences between patients who did not develop any or only mild grade (G) 1 irAE and patients who experienced clinically relevant irAE, specifically G2 and higher.

Results

We consecutively enrolled 63 patients. The median age was 66 years, with 19 (30.2 %) being female. Histological tumor types included 31 patients with melanoma, 22 with non-small cell lung cancer, 8 with renal carcinoma, and 5 with other malignancies. The majority of patients initiated treatment as first-line therapy (35 patients, 53 %). Out of these patients, 39 (61.9%) did not experience any irAEs, while 14 patients had G1 toxicity (22.2%), 10 patients (15.9%) had G2 toxicity, and 1 patient (1.6%) had G3 toxicity. G4 or G5 toxicity was not observed. Using the Mann-Whitney test, we determined that patients who did not experience any or mild (G1) immunologically mediated toxicity during treatment had significantly lower level of T helper lymphocytes CD4+ in peripheral blood before the initiation of treatment (P=0.034) compared to patients who experienced G2 or G3 toxicity during treatment. Additionally, they had lower level of naive T lymphocytes CD4+RO-CD27+ (P=0.012), lower level myeloid dendritic cells CD4-HLADR+ (P=0.040), and higher level of memory lymphocytes CD4+RO+CD27+ (P=0.006).

Conclusions

Our results support the hypothesis that initial flow cytometry parameters detectable in peripheral blood could significantly predict irAE. These findings need to be validated in a larger patient population.

Legal entity responsible for the study

The authors.

Funding

Ministry of Health of the Czech Republic, grant nr. NV18-03-00339.

Disclosure

All authors have declared no conflicts of interest.