Study On Early Risk Factors Of Clinical Features For IrAEs In Primary Hepatocellular Carcinoma Treated With PD-1 Antibody Combined With TKI And The Relationship Between IrAEs And Outcomes

Objective:Through observational study,to identify the early risk factors of immune-related adverse events(irAEs)in patients with primary liver cancer treated with programmed death-1(PD-1)antibody combined with tyrosine kinase inhibitors(TKI)from clinical features,and the relationship between irAEs and clinical outcome was also analyzed.Methods:1.Firstly,130 patients with primary liver cancer were divided into irAEs group and non-irAEs group according to whether irAEs occurred during PD-1 antibody combined with TKI treatment.And according to the severity of irAEs,it was divided into two subgroups:mild irAEs group with grade<2 irAEs and severe irAEs group with grade≥3 irAEs.2.The baseline and the changes of clinical features(body temperature,body mass index,nature of defecation,cancer related pain,etc.)within one week after the first treatment of primary liver cancer with PD-1 antibody combined with TKI of all patients were recorded.The differences between irAEs group and non-iraEs group,between irAEs ≤2 grade and irAEs ≥3 grade were analyzed by logistics regression analysis.Identify clinical features that can be used as early risk factors for irAEs.3.Based on patients’ survival status at the end of follow-up,the relationship between irAEs and overall survival(OS)and progression-free survival(PFS)was analyzed by Kaplan-Meier survival curve.At the same time,COX regression analysis was used to find out the relationship between patients’ survival outcome and irAEs related clinical features.Results:1.Among the 130 patients,74 patients developed irAEs and 56 patients did not.The overall incidence of irAEs was 56.92%,the incidence of Grade 1/2 irAEs was 39.23%and the incidence of Grade 3/4 irAEs was 17.69%.The most common irAEs were fever in 45 cases(24.73%),digestive system irAEs in 25 cases(13.74%)and skin related irAEs in 24 cases(13.19%).The most common Grade 1/2 irAEs was fever(45 cases,24.73%),and the most common Grade 3/4 irAEs was hepatitis(7 cases,3.85%).Overall objective response rate(ORR)and disease control rate(DCR)were 16 cases(12.3%)and 63 cases(48.5%),respectively.The objective response rate(ORR)and disease control rate(DCR)in the group no-irAEs were 9.3%and 51.2%,respectively.The ORR and DCR of irAEs group were 17.1%and 58.6%,respectively.2.Except for Alanine aminotransferase(ALT),there was no significant difference in other indicators between the irAEs group and the non-irAEs group at baseline(P>0.05).The patients in Grade 3/4 irAEs group were more likely to have prolonged Prothrombin time(PT)and elevated ALT at baseline.Within one week after the first treatment,patients with irAEs tended to have fever,aggravation of cancer-related pain,and change of bowel habits(P<0.05).After excluding the effect of fever in irAEs,logistics regression analysis found that fever and aggravation of cancer-related pain within one week of initial treatment were independent risk factors for irAEs(P<0.001,OR:14.773,95%CI:4.948-44.106).3.There were no significant differences in objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS)and overall survival(OS)between irAEs and non-irAEs groups(P>0.05).OS of patients with non-irAEs was better than that of patients with Grade 3/4 irAEs.There was no statistical difference in OS between patients without irAEs and Grade 1/2 irAEs.In addition,baseline body mass index(BMI)and fever within a week after initial treatment had statistically significant effects on OS(P<0.05).Conclusion:Fever and aggravation of cancer-related pain within one week of initial treatment were independent risk factors for irAEs.There was no significant relationship between low-level irAEs and outcomes,and severe irAEs suggest a poor prognosis.Baseline BMI and fever within one week of first treatment were the factors affecting OS,while age and low BMI were the factors that affected patients’ PSF.