Analysis Of Characteristics,predictive Factors And Correlation With Survival Outcomes Of Immunotherapy-related Adverse Events

Background and objective:In recent years,a wide variety of immune checkpoint inhibitors(ICIs)is emerging and has shown long-lasting and significant efficacy in the treatment of various malignant tumors.However,about 10%of patients experience severe and even life-threatening immune-related adverse events(irAEs).Therefore,it is of great clinical value to fully understand the characteristics of irAEs and explore the factors that can predict the occurrence of irAEs early.We aimed to retrospectively analyze the characteristics and related predictors of irAEs,as well as the correlation between irAEs and survival outcomes in patients with advanced pan-cancer who were treated with multi-type ICIs in real-world.Methods:We retrospectively analyzed data from 105 patients with advanced pan-cancer who were treated with multi-type ICIs in the First Hospital of Jilin University from Jan1,2016 to Aug 1,2020.We used logistic regression analyses to investigate associations between irAEs and clinical baseline characteristics,blood count parameters,and biochemical indicators during the treatment.Receiver-operating characteristic curve was used to determine a cutoff value for parameters and area under the curve.The cutoff point was determined using Youden’s index.Kaplan–Meier and cox multivariate regression analysis were performed to estimate the relationship of baseline characteristics and irAEs with progression-free survival(PFS)and overall survival(OS).Results:A total of 105 patients with advanced pan-cancer treated with ICIs were included in this study.1.Overall,the incidence of irAEs and the overall toxicity profile were consistent with previous studies of treatment with ICIs.The incidence of irAEs was 39.05%(41/105 patients),including 20"multi-site"irAEs and 21"single-site"irAEs;the incidence of irAEs of grade≥2 was 19%(20/105 patients)and irAEs of grade≥3 was9.5%(10/105 patients).The time to the first occurrence of ir AE was 1.4 months,and the majority(87.8%)of patients had the first occurrence of ir AE within 3 months after administration.All patients in our study were managed for irAEs according to the Clinical Practice Guideline.2.The study explored predictors of irAEs.We found that lower relative lymphocyte count(RLC)(cutoff=28.5%),higher albumin(ALB)(cutoff=39.05g/L)and higher absolute eosinophil count(AEC)(cutoff=0.175×10~9/L)were significantly associated with the occurrence of irAEs,of which a higher AEC(cutoff=0.205×10~9/L)was strongly associated with skin-related irAEs(OR=0.163;P=0.004);And a higher lactate dehydrogenase(LDH)level(cutoff=237.5U/L)was an independent predictor of irAEs of grade≥3(OR=0.083;P=0.023).3.In the analysis of immune cell subgroup,a lower absolute count of CD8~+CD28~-regulatory T cells(OR=0.806;95%CI:0.643-1.011;P=0.062)was associated with the occurrence of irAEs,although the difference was not statistically significant;And a higher percentage of CD19~+B cells were associated with the occurrence of irAEs of grade≥3(P=0.02)and grade≥2(P=0.051).4.The study explored the correlation between irAEs and survival outcomes.The results showed that patients with irAEs had a significantly better PFS(8.37 vs 3.77months;HR=2.02;P=0.0038)and OS(24.77 vs 13.83 months;HR=1.84;P=0.024),and the differences were statistically significant.Conclusions1.This retrospective study reported the clinical profile data of irAEs of unselected patients in the real world,with unique patient characteristics.2.RLC,ALB,and AEC were significantly associated with the occurrence of irAEs;AEC was more closely associated with the occurrence of skin-related irAEs;and LDH was independently associated with the occurrence of irAEs of grade≥3.3.There was a trend of correlation between a lower absolute count of CD8~+CD28~-regulatory T cells and the occurrence of irAEs.4.Patients with irAEs of any grade had better efficacy and clinical outcomes.