Incidence And Risk Factors Of Lung Injury In Patients With Advanced Malignant Tumor Treated With PD-1 Immune Checkpoint Inhibitor

Background: In the past decade or so,the emergence of a new class of immune checkpoint inhibitors(ICIs)has greatly influenced the methods of tumor treatment.In2013,ipilimumab was approved by the European Union for metastatic melanoma,and pembrolizumab and nivolumab were also approved successively in the following year.Nivolumab and pembrolizumab have also been approved by the FDA for use in second line metastatic non-small cell lung cancer(NSCLC)and positive NSCLC for programmed death-ligand 1(PD-L1),while Nivolumab has also been approved for use in the treatment of renal cell carcinoma(RCC).Anti Programmed cell death 1(PD-1)and anti PD-L1 can avoid certain tumor immune escape mechanisms,block immune checkpoint cytotoxic T lymphocyte antigen 4(CTLA-4)and PD-1 promote effector T cell activation and proliferation,thereby enhancing cellular immunity and restoring the anti-tumor response of the patient’s immune system.ICIs is becoming a widely used treatment for cancer and have significant effects in many cancer treatments.However,ICI has developed immune related adverse events(ir AEs)in clinical use.ir AEs often accumulate in organs such as the skin,gastrointestinal tract,endocrine system,liver,lungs,etc.Among them,the lung related adverse reactions(CIP)caused by ir AEs are particularly severe.The occurrence of this adverse reaction has a significant impact on the quality of life and prognosis of patients after treatment,and even endangers their health and life in the most severe cases.Objective: A retrospective analysis of immune related lung injury caused by PD-1inhibitors in ICIs can help us more effectively understand the treatment related adverse reactions and factors of immunosuppressants,and provide choices for clinical medication.Method: 1.Study subjects: 165 patients with advanced malignant tumors who were treated with PD-1 inhibitors(mainly Carolizumab,Tirolizumab,and Xindilizumab)from February 2021 to January 2022 at the First Affiliated Hospital of Anhui Medical University were collected and screened.2.Research methods: by retrospective analysis of their clinical data,the age,clinical sex,combined basic diseases,smoking history and alcoholism history of the enrolled patients,as well as the type of cancer,cancer staging diagnosis,previous tumor treatment plan,whether to operate,PD-1 monoclonal antibody type,whether to have combined treatment,whether to have adverse reactions after treatment and whether to die),Analyze the occurrence and related risk factors of lung related injury after PD-1inhibitor treatment.3.Statistical analysis method: The included objects are grouped based on whether CIP has occurred,and t-test is used for inter group comparison χ 2 Inspection;Logistic regression was used for analysis of related factors.When P<0.05,it has statistical significance.Result: 1.Out of 165 patients receiving ICIs treatment,9 patients experienced varying degrees of CIP,and the overall incidence of CIP in this study was 5.45%.In the 9 cases of CIP in this study,the median adverse reaction grade was G2,and one patient(11.11%)experienced severe respiratory failure and died.Five patients(55.56%)received symptomatic treatment with antibiotics,two patients(22.22%)received steroids,and two patients did not receive medication due to only imaging changes.The occurrence of CIP is usually early,often occurring after the first two cycles of treatment with ICIs.Among them,6 cases(66.67%)interrupted subsequent ICIs treatment due to CIP,and 3cases(33.33%)continued to use ICIs after treatment.2.A comparison was made between the CIP group and the non CIP group using t-tests or chi square tests,and it was found that there were significant differences(P<0.05)in long-term smoking history,combined with other treatment methods,and tumor efficacy evaluation between the two groups.These results indicate that there may be a correlation between long-term smoking,combination of other tumor treatments,and tumor efficacy with the occurrence of CIP.3.Logistic regression analysis was used to analyze the relevant influencing factors of CIP,and the results showed that smoking history(OR=7.643,95% CI: 1.532-38.137)and combination with other tumor treatments(OR=10.909,95% CI: 1.332-89.351)were the relevant risk factors affecting the occurrence of CIP(P<0.05).Conclusion: 1.The incidence of CIP is relatively low.The adverse reactions of most patients are moderate.Half of the patients with adverse reactions need to stop treatment with anti PD-1 monoclonal antibodies.2.The combination of anti PD-1 monoclonal antibody and other treatment methods,as well as smoking index,are related factors that affect the occurrence of CIP.