Correlation Of Peripheral Blood Chemistries With Immune Checkpoint Inhibitor-associated Pneumonia In Lung Cancer

Objective(s):To analyze the relationship between peripheral blood tests(absolute lymphocyte count(ALC),eosinophil count(AEC),albumin(ALB),lactate dehydrogenase(LDH),neutrophil-to-lymphocyte ratio(NLR),lymphocyte-to-monocyte(LMR))and diagnosis,severity and prognosis of CIP in lung cancer patients,with the aim of identifying potentially at-risk populations in the clinic and improving the benefit of immune checkpoint inhibitor(ICIs)therapy in lung cancer patients.Methods:This case-control study retrospectively analysed 51 patients with CIP who met the inclusion criteria and 51 normal patients without CIP which selected according to 1:1 random unmatched selection from January 1,2019 to June 1,2022.The basic clinical data and the different laboratory indicators at the baseline,at the onset of CIP and before the last dose of ICI were collected from these patients,and all patients were followed up by telephone for overall survival.Measures were expressed as conforming to a normal distribution using±S and percentages(%),with independent samples t-test for comparison between two groups and ANOVA for multiple group comparisons.In contrast,those with non-normal distribution were described by M(P25,P75)and comparisons between two groups were made using non-parametric rank sum test.Pre-post changes in laboratory indicators between the two groups were assessed using paired t-tests or paired rank sum tests.Comparisons between groups for count data were made using the?2 test or Fisher’s exact probability method,and rank sum tests were used for rank variable data.The independent factors associated with the occurrence of CIP were analysed by means of a multifactorial logistic regression model;the diagnostic value of each laboratory test as an aid to CIP was analysed using receiver operator characteristics curve(ROC)curves;the factors influencing severe CIP were analysed in the subgroup with CIP using a multifactorial logistic regression model;the Kaplan-Meier method was used to analyse the relationship between different peripheral blood tests on the prognosis of CIP patients,to draw survival curves,and to analyse the independent risk factors affecting the prognosis of CIP patients using a multifactorial Cox proportional risk model.A rank correlation coefficient test was used to assess the linearity of the relationship between the two variables.Results:1.The total of 788 cases of lung cancer patients treated with ICIs were reviewed in this study.51 patients developed CIP.The incidence of CIP was 6.47%,the incidence of severe CIP was 2.53%,the median time to CIP onset was 4.43 months(0.5-19months),and the median dosing cycle was 4 cycles(1-20 cycles).The median OS for patients with CIP was 12.7 months(95%CI:10.7-14.68 months),one-year survival rate was 41.18%.2.Univariate and multivariate logistic regression analyses showed that previous chest radiotherapy and male patients were independent correlates of CIP(P<0.05);univariate logistic regression analysis showed that ALC,ALB,LMR and NLR were associated with the development of severe CIP(P<0.10)when CIP symptoms occurred,and multivariate logistic regression analysis showed that ALC≤0.92?10~9/L was an independent correlate of the occurrence of severe CIP(P<0.05).3.The results of ROC curve analysis showed that the area under the curve(AUC)of ALC,ALB,NLR,LMR and LDH were 0.839,0.825,0.759,0.799 and 0.615respectively,all of which were statistically significant(P<0.05);they have an auxiliary diagnostic value for the occurrence of CIP.4.Spearman’s correlation coefficient test showed a rank correlation between the percentage decrease in lymphocyte,T-cell and Ts-cell counts from baseline and the grade of CIP(P<0.05).5.Kaplan-Meier method of plotting survival curves showed that median OS was significantly better in patients with ALC>0.92?10~9/L at the onset of CIP than in those with ALC≤0.92?10~9/L(6.77 months vs not reached(NR),P=0.001).6.The results of the univariate Cox proportional risk model analysis showed that ALC at the onset of CIP symptoms,CIP severity,number of treatment lines and NLR were significant factors affecting the prognosis of CIP patients(P<0.10);the results of the multi-factor Cox proportional risk model analysis showed that patients with severe CIP at the onset of CIP had a poor prognosis(P<0.05).Conclusion(s):Patients who with previous chest radiotherapy and men patients are potentially at high risk of developing CIP.Clinical indicators such as ALC,ALB,NLR,LMR,LDH can assist in the diagnosis of CIP when patients present with new respiratory symptoms or chest imaging changes.There is a correlation between the percentage decrease in lymphocytes,T cells and Ts cells compared to baseline and the grade of CIP.When CIP symptoms occur,ALC≤0.92?10~9/L is a high risk factor for the occurrence of severe CIP,and patients with severe CIP have a poor prognosis.