Application Of Peripheral Blood Markers To Predict Immune-Related Toxicity And Prognosis In Patients With Advanced Non-Small Cell Lung Cancer

Objective:In recent years,immunotherapy for malignant tumors has ushered in a new era of tumor therapy.Patients with advanced non-small cell lung cancer(non-small cell lung cancer,NSCLC)benefit from immunotherapy.However,with the increase of clinical application,immunotherapy may cause mild or severe immune-related adverse events(ir AEs).Immune checkpoint inhibitors(ICIs)themselves play a role at the immune level.They block immune escape by combining PD-1(programmed cell death-1)/PD-L1(programmed cell death-Ligand 1).While enhancing cellular immunity against tumor,ICIs may also enhance the normal immune response of the body,thus leading to the disorder of immune response,even leading to ir AEs.Therefore,in clinical practice,it is extremely urgent to find accurate and reliable biomarkers for predicting the occurrence and prognosis of immune-related adverse events.Peripheral blood inflammatory markers are considered to be one of the most convenient indicators to predict the above results.The purpose of this study is to explore the relationship between peripheral blood inflammatory markers of patients with advanced NSCLC treated with immunocheckpoint inhibitors and the incidence and prognosis of ir AEs in real world clinical practice.To clarify the correlation between the two in order to better guide and serve the clinic.Methods:The clinicopathologic data,efficacy,adverse events and prognosis of 92 patients from the First Affiliated Hospital of Dalian Medical University with advanced NSCLC treated with immune checkpoint inhibitor from July 30,2018 to August 31,2022 were retrospectively collected.Response Evaluation Criteria in Solid Tumors(RECIST)1.1 was applied to evaluate the tumors.ir AEs were evaluated according to The NCI Common Terminology Criteria for Adverse Events(NCI-CTCAE)5.0 of the National Cancer Institute.Logistic regression model was used to evaluate the risk factors of ir AEs.Cox regression model was used to evaluate the effect of Low/High neutrophil to lymphocyte ratio(NLR)and Low/High platelet to lymphocyte ratio ratio(PLR),Low/High monocyte to lymphocyte ratio(MLR),and Low/High systematic immune-inflammation index(SII)on overall survival(OS)and progression-free survival(PFS).The survival curve was drawn by K-M method.Results:A total of 92 patients were included in this study.Among them,79 were male(85.9%)and 13 were female(14.1%);80 cases(87.0%)were treated with PD-1 inhibitor and 12 cases(13.0%)with PD-L1 inhibitor.All patients can be evaluated adverse events.A total of 48 patients were observed 110 ir AEs,of which 12 were reported with grade>2.20patients(21.7%)had single ir AEs,and 28(30.4%)had multi-system ir AEs.The baseline NLR,PLR and SII levels of patients with non-ir AEs(non-immune-related adverse events)were higher than those of patients with ir AEs(P<0.05).No matter whether the patients had ir AEs or not,there was no statistical difference in ORR and DCR(ORR: 45.8% vs 40.9%,P>0.05;DCR: 93.8% vs 95.5%,P>0.05).At the onset of ir AEs,the level of NLR,MLR and SII were significantly lower than the baseline(P<0.05);The PLR level showed an upward trend compared with the baseline,but there was no statistical difference(P>0.05).In ROC analysis,the area under the curve of NLR(AUC=0.616,95% CI: 0.501-0.731)is the largest.Through single factor logistic analysis,no independent risk factors leading to ir AEs were found.After immunotherapy,ir AEs patients had longer m OS than non-ir AEs patients(m OS,34.5 months vs 11.3 months,P<0.05).Subgroup analysis of patients with single and multiple ir AEs showed that there was no significant difference in survival outcomes between the two groups(P>0.05).Multivariate COX analysis showed that treatment less than 4 cycles was an independent risk factor for PFS;Smoking and no ir AEs were independent risk factors for OS.Conclusion:In this study,the NLR,MLR and SII of patients with advanced NSCLC treated with PD-1/PD-L1 inhibitor alone or combined with other treatments showed a downward trend when ir AEs occurred,and L-NLR had a higher predictive value for the occurrence of ir AEs.Compared with patients with advanced NSCLC without ir AEs,patients with ir AEs may have a better prognosis and ir AEs could be a possible marker for evaluating the prognosis of those patients.