Predictive Value Of Immune Cell Levels For Immune-related Adverse Events In Patients With Advanced Non-small Cell Lung Cancer ——A Single-institution Retrospective Study

Background and objective:The emergence of immune checkpoint inhibitors（ICIs）has promoted the development of immunotherapy for malignant tumors.It cannot be ignored that when drugs activate the host’s immune system,they can also cause serious and even life-threatening immune-related adverse events（ir AEs）.Simultaneously based on the crucial role of immune cells in the human immune response.Therefore,We aimed to retrospectively analyze the clinical characteristics of ir AEs in patients with advanced non-small cell lung carcinoma（NSCLC）who were treated with ICIs in real-world,and to explore the predictive value of immune cells for the occurrence of ir AEs.Methods:We retrospectively analyzed the data from 113 advanced NSCLC lung cancer patients who were treated with ICIs and completed immune cell level detection in Zhejiang Provincial People’s Hospital from December 31,2017 to December 31,2021.Univariate and multivariate logistic regression models were used to determine the related predictors of ir AEs.And Receiver-operating characteristic curves（ROC）were used to determine cutoff values for these predictors.Kaplan-Meier survival analysis were performed to estimate the relationship of ir AEs and the predictors of ir AEs with progression-free survival（PFS）.Results:1.The incidence of ir AEs was 32%（36/113 patients）,20 people had one ir AEs,and16 people had multiple ir AEs.The most common ir AEs were immune-related pneumonitis,followed by hypothyroidism,hepatitis,and skin reactions.The incidence of ir AEs of grade≥3 was 22.12%（25/113 patients）,and 3 deaths caused by ir AEs were all related to immune-related pneumonia.Most patients（69.4%）developed the first occurrence of ir AEs within 3 months after ICIs starting.2.This study explored predictors of ir AEs.We found that higher Th1 ratio at baseline（cutoff=17.62%）,higher Th2（critical=33.5%）and lower total Treg ratio（critical=4.77%）at 4-6 weeks after ICIs starting were independent predictors associated with the occurrence of ir AEs in all patients.In addition,we also analyzed the predictors of ir AEs in the subgroup of ICIs monotherapy,and the results were consistent with the predictors of ir AEs in all patients.3.In the analysis of predictive factors of ir AEs of grade≥3,we found that the white blood cell count（cutoff value=6.85×10~9/L）and the Th2 ratio at 4-6 weeks after ICIs starting（cutoff value=35.5%）were independent predictor of ir AEs of grade≥3.4.This study explored the relationship of ir AEs and the predictors of ir AEs with survival outcomes.The results showed that higher levels of Th2 cells at 4-6 weeks after ICIs starting predicted longer PFS（median PFS:8.2 months vs 5.0 months,p=0.001）;and patients with ir AEs had significantly better PFS than those without ir AEs（median PFS:8.3 months vs 4.5 months,p=0.003）.Conclusions:1.This single-institution retrospective study reported the clinical characteristics of ir AEs of advanced NSCLC patients in the real world.2.Analysis of predictors of ir AEs showed that in immune cells,higher Th1 ratio at baseline,lower total Treg ratio and higher Th2 ratio at 4-6 weeks of ICIs treatment were independent factors for the occurrence of ir AEs.White blood cell counts and higher Th2 ratios at 4-6 weeks of ICIs treatment were independently associated with the occurrence of ir AEs of grade≥3.3.Patients with ir AEs predicted longer PFS.High levels of Th2 cells at 4-6 weeks after ICIs treatment were associated with better survival outcomes（PFS）.