Meta-analysis And Influencing Factors Of Adverse Events Of Immune Checkpoint Inhibitors Plus Chemotherapy

Objective:The first part of this research is to find out the adverse events spectrum of immunotherapy plus chemotherapy,the second part of this research is to explore the risk factors of immune related adverse events in patients treated with immunotherapy plus chemotherapy,so as to provide the basis for the management of adverse events and guarantee the safety of patients treated with immunotherapy plus chemotherapy.Methods:1.Meta-Analysis:the databases of Pub Med,Wan Fang,EMBASE,CNKI,Wei Pu and Cochrane library were searched systematically.The inclusion and exclusion criteria of clinical studies were in accordance with the PICO principle of evidence-based medicine(population,intervention,comparision and outcomes),and the data were extracted from each study according to the preset table.The evaluation criteria were established by Cochrane bias risk assessment tool To estimate the potential risk of bias in these clinical trials,R software(version 3.6.1)was used for statistical analysis of evidence synthesis Influencing factor analysis:187 cases of patients in our hospital were selected from January 2018 to December2020.Using the method of retrospective study,standardized data extraction form was designed and case information was collected.The incidence of immune related adverse events and the occurrence of various organ systems were counted.Chi square test was used for single factor analysis Logistic regression analysis was used to screen out the risk factors of immune related adverse events.Results:Nineteen clinical trials were included in the meta-analysis,including 4292 patients receiving immunotherapy plus chemotherapy.The 19 included articles were well designed and the results were complete.The main adverse events of immune checkpoint inhibitors combined with chemotherapy in the treatment of malignant tumors were hematological adverse events(leukopenia,anemia,thrombocytopenia,thrombocytopenia,neutropenia),gastrointestinal adverse events(nausea,vomiting,loss of appetite,diarrhea,constipation,colitis),and respiratory adverse events(cough,dyspnea,pneumonia)Liver toxicity(elevated alanine aminotransferase and aspartate aminotransferase),skin toxicity(pruritus and rash),endocrine system adverse events(hypothyroidism)and other adverse events(transfusion reaction,alopecia,fatigue,peripheral neuropathy,stomatitis,fever,arthralgia and weakness).The five adverse events with the highest incidence were anemia(incidence=0.52,95%CI,0.40-0.63,I~2=98%,P<0.01),nausea(incidence=0.40,95%CI,0.33-0.49,I~2=91%,P<0.01),neutropenia(incidence=0.38,95%CI,0.29-0.48,I~2=93%,P<0.01),fatigue(incidence=0.32,95%CI,0.25-0.39,I~2=89%,P<0.01),01),thrombocytopenia(incidence=0.30,95%CI,0.23-0.38,I~2=96%,P<0.01).The study of influencing factors found that in187 cases of patients with combined immunochemotherapy,a total of 59 patients had immune related adverse events,and the incidence of immune related adverse events was 31.55%.Univariate analysis and chi square test showed that there was an immune correlation.The occurrence of sexual adverse events was related to gender,immunotherapy cycle and number of treatment lines(P<0.05),but not to age,weight,glucocorticoid use or not and cancer type(P>0.05).Logistic regression analysis showed that gender and immunotherapy cycle were independent risk factors for immune related adverse events(P<0.05).Conclusion:1.The adverse events of immunotherapy combined with chemotherapy are characterized by the superposition of the spectrum of adverse events of immunotherapy and chemotherapy,which should be managed and monitored according to the guidelines in clinical application;2.Gender and immunotherapy cycle are independent risk factors of immune related adverse events,and immune related factors should be closely monitored in the first few cycles of immunotherapy More attention should be paid to female patients.