| Objective:To explore the correlation between C-reactive protein-albumin ratio(CAR)and systemic immune-inflammation index(SII)in peripheral blood of multiple myeloma(MM)patients with their clinical features such as immunophenotype and cytogenetics,as well as the clinical significance and prognosis,this study have compared the difference of the levels of CAR and SII in peripheral blood(PB)between MM patients and healthy population.Methods:The subjects of this study were 313 patients admitted to Qingdao University Affiliated Hospital from February 2014 to September 2020 who met the diagnostic criteria of the International Myeloma Working Group(IMWG)and were newly diagnosed and chemotherapy naive patients.Exclusion criteria: 1.Patients who have received chemotherapy,combined with other tumors,and renal insufficiency at the initial diagnosis;2.Patients with chronic or acute infection;3.Patients with active rheumatic disease.4.Patients with acute and chronic liver disease.5.Patients with incomplete clinical data or lost follow-up.After exclusion,186 MM patients with initial treatment were enrolled as the patient group and 50 healthy people were enrolled as the control group.Various clinical data including gender,age,C-reactive protein,hemoglobin,serum lactate dehydrogenase level,serum albumin,β2-microglobulin(β2-MG),platelets,bone marrow plasma cell ratio,extramedullary infiltration,creatinine,serum calcium,conventional chromosomal karyotype,cellular immunophenotype,cytogenetics,and indicators of Durie-Salmon(DS)staging,international staging system(ISS)staging,revised international staging system(RISS)staging,etc.were analyzed retrospectively.CAR was calculated as C-reactive protein(CRP)/serum albumin(ALB).The formula for calculating SII is platelet(P)× neutrophil(N)/lymphocyte(L).The CAR and SII values were calculated,and the peripheral blood CAR and SII values of the MM patients and the healthy control group were compared.Through the receiver operating characteristic curve(ROC),the area under the curve(AUC)was analyzed and calculated,and the optimal cut-off values of CAR and SII were determined to be 0.211 and 116.15,respectively.The CAR and SII values of newly treated MM patients were divided into group with CAR>0.211(n=69),group with CAR≤0.211(n=117),group with SII>116.15(n=31),and group with SII≤116.15 group(n=155),the correlation between CAR,SII and basic clinical data such as immunophenotype,cytogenetics and staging was analyzed,and the influence of each factor on the prognosis of newly diagnosed multiple myeloma(NDMM)patients was analyzed.The difference analysis of categorical data between groups was performed by χ2 test or Fisher test,and the difference comparison of measurement data between groups was calculated by independent sample T test or nonparametric test.The correlation between parameters and survival time was analyzed by Kaplan-Meier method,and the survival curve of parameters was drawn.Cox regression analysis was performed for multivariate analysis,and P<0.05 was considered to be statistically significant.Results:1.186 NDMM patients were finally enrolled in this study,including 101 males(54.3%)and 85 females(45.7%).The median age was 63(30-83)years,and the median bone marrow plasma cell percentage was 24%(0 %～98.5%).Types: Ig G type(n=76,40.9%),Ig A type(n=51,27.4%),and light chain and other type(n=59,31.7%).148patients(84.6%)were in stage III in DS stage,79 patients(46.5%)in stage III of ISS stage,49 patients(46.7%)in stage III of R-ISS stage,and 54 cases(29%)in serum lactate dehydrogenase> Upper limit of normal(ULN),32 patients(17.4%)with serum calcium >ULN,immunophenotype: CD56 positive patients in 61 patients(53.0%),negative patients in 54 patients(47.0%),CD117 positive patients in 22 patients cases(19.8%)and 89(80.2%)negative patients.In addition,53 patients(28.5%)had increased CRP(>10mg/L),and 117 patients(62.9%)had decreased ALB.After a median follow-up of 23 months,70 patients(37.6%)developed progression and 72 patients(38.7%)died during the follow-up period.The median progression-free survival time(PFS)and overall survival time(OS)were not reached.2.Through the difference analysis,it was found that the peripheral blood CAR and SII of the newly treated MM patients were higher than those of the healthy control group,and the difference was statistically significant(P<0.05).K-M survival analysis was performed on NDMM patients with high CAR,low CAR,high SII,and low SII,respectively,and it was found that the high CAR group had shorter OS and PFS than the low CAR group,and the high SII group had a shorter time than the low SII group.The OS of NDMM patients in the high CAR and high SII group was poor.Univariate survival analysis showed that ISS stage III,elevated serum Ca,extramedullary infiltration,cytogenetic abnormality TP53 positive,and high CAR group were associated with shorter PFS;DS stage III,ISS stage III,elevated serum Ca High,extramedullary infiltration,cytogenetic abnormal RB-1 positive,high CAR group,and high SII group were associated with shorter OS.The independent factors with P<0.05 in the univariate analysis were included in the multivariate analysis of the Cox regression model.The results showed that CAR,extramedullary infiltration,TP53,elevated blood calcium,and thrombocytopenia were independent prognostic factors for PFS.CAR,extramedullary invasion,and SII were independent prognostic factors for OS.3.Efficacy analysis: ROC curve was used to detect the sensitivity,specificity,area under the curve(AUC)and critical value of CAR and SII.The AUC of CAR was 0.840,the cutoff value was 0.211,the sensitivity was 71.23%,and the specificity was 84.96%.The AUC of SII was 0.593,the cutoff value was 116.15,the sensitivity was 27.4%,and the specificity was 89.29%.It shows that the inflammation-related biomarker CAR has a high prognostic accuracy in NDMM patients.The correlation analysis between groups showed that the treatment effect of patients in the low CAR group was better than that of the patients in the high CAR group,the difference was significant(P<0.05).The 1-,3-,and 5-year overall survival and progression-free survival rates in the low CAR group were higher than those in the high CAR group.The K-M survival analysis showed that in NDMM patients treated with immunomodulators,proteasome inhibitors,and the combination of the two drugs,there were significant differences between the high CAR group and the low CAR group.It shows that MM’s response to the current novel drugs is not durable,can escape these powerful immunotherapy strategies,and cannot eliminate the poor prognosis of high CAR.Conclusion:1.The inflammation-related biomarker CAR is an independent prognostic factor for multiple myeloma,and high CAR level in newly treated multiple myeloma patients often indicates poor prognosis.2.The treatment effect of patients in the low CAR group is better than that of the patients in the high CAR group,and it is easy to obtain deep remission.Current new drugbased treatment regimens maybe cannot improve the poor prognosis of patients in the high CAR group. |
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