Establishment Of Prognostic Model Of Newly Diagnosed Multiple Myeloma

Background and objective:Multiple myeloma(MM)is a malignant proliferative disease of plasma cells,the incidence of which ranks second in hematological malignancies.It is still an incurable disease.The clinical manifestations,curative effects,and prognostic survival of MM are highly heterogeneous.In the past ten years,with the widespread application of new drugs and autologous hematopoietic stem cell transplantation(ASCT),the patients'survival has been significantly improved,but not all patients can benefit from it,and individual survival differences are still significant.This poses a challenge to many commonly used MM risk stratification/prognosis evaluation systems(mainly including R-ISS staging,International Myeloma Working Group(IMWG)2014/2016 risk stratification criteria,Mayo Clinic mSMART 3.0,etc.),therefore,objective and accurate risk stratification and prognostic evaluation during diagnosis will help to better predict the prognosis and formulate individualized treatment plans.The MM disease stage/risk stratification is the same,but there is still great heterogeneity.The purpose of this study is to establish a prognostic score system suitable for the newly diagnosed multiple myeloma population in China through our cohort study.Methods:Retrospective analysis of clinical data of 841 NDMM patients from February 2003 to July2019,Cox univariate and multivariate regression analysis of risk factors affecting OS,combined with Cox proportional regression coefficients to assign weights to independent adverse prognostic factors establish a prognostic model,and verify the model based on ISS/R-ISS stage,cytogenetic abnormalities,and age.Results:1.Univariate and multivariate survival analysis:univariate analysis showed that age?65 years,ISS stage III,R-ISS stage III,platelet count<100×10~9/L,hemoglobin<100 g/L,LDH?220 U/L,serum?2 microglobulin?5.5 mg/L,bone marrow plasma cell ratio?30%,eGFR?40 ml/1.73m2*min,corrected serum calcium(CsCa)?2.75 mmol/L,and HRCA all affect OS bad prognostic factors.Multivariate analysis showed that age?65years(HR=1.513,95%CI=1.114~2.056,P=0.008),platelet count<100×10~9/L(HR=1.804,95%CI=1.242~2.619,P=0.002),hemoglobin<100 g/L(HR=1.631,95%CI=1.077~2.470,P=0.021),HRCA(HR=2.072,95%CI=1.393~3.081,P<0.001)affect the OS independent poor prognostic factor.2.Establishment of prognostic model:Incorporate the above four independent adverse prognostic factors(age?65 years old,platelet count<100×10~9/L,hemoglobin<100g/L,HRCA)into the model,and assign 0.5 points,1 point,0.5 points,1 point respectively,calculate the prognostic index(PI)of each NDMM patient.Of the 841 NDMM patients,560NDMM patients with PI were included in the validation cohort,and 281 NDMM patients had no PI,so they were not included in the analysis.The model is divided into 3 groups according to different PI:the low risk group:0?PI?1,The median OS was 58 months;the intermediate risk group:PI=1.5 points,the median OS was 31 months;the high risk group:2?PI?3points,the median OS was 16 months(P<0.001),of which 240 cases(42.9%)were in the low risk group,130 cases(23.2%)were in the intermediate risk group,and 190 cases(33.9%)were in the high risk group.The risk of death in the high-risk group was three times higher than in the low-risk group(P<0.001).3.Validation of prognostic models:(1)ISS staging:A total of 549 NDMM patients with PI and ISS staging results were included.A total of 235 NDMM patients were included in stage I~II,of which 146 were low risk groups,39 cases were in the intermediate risk group and 50 in the high risk group.Survival analysis showed that the median OS of the three groups was 66 months,34 months,and 25 months(P<0.001).A total of 314 NDMM patients were included in stage III,of which 88 were in the low risk group,90 were in the intermediate risk group,and 136 were in the high risk group.Survival analysis showed that the median OS of the three groups was 43 months,29 months,and 13 months(P<0.001).In summary,the prognostic model can further stratify NDMM patients in ISS stage I to II and III patients.(2)R-ISS stages:A total of 513 NDMM patients with PI and R-ISS stage results were included.A total of 269 NDMM patients were included in stage I~II,of which 174 were in the low risk group,42 were in the intermediate risk group,53 The case is a high risk group.Survival analysis shows that the median OS of the three groups is 59 months,41 months,and 25 months(P<0.001),further analysis shows:A total of 239 NDMM patients were included in stage II,of which 146 were in the low risk group,42 were in the intermediate risk group,and 51 were in the high risk group.Survival analysis shows that the median OS of the three groups is 58months,41 months,and 25 months(P<0.001).A total of 244 NDMM patients were included in stage III,including 38 in the low risk group,87 in the intermediate risk group,and 119 in the high risk group.Survival analysis showed that the median OS of the three groups was 36months,28 months,and 13 months(P<0.001).In summary,the prognosis model can further stratify NDMM patients in R-ISS stage I to II and III patients.(3)Cytogenetic abnormalities:A total of 460 NDMM patients with PI and CA results were included.SRCA included a total of127 NDMM patients,including 108 in the low risk group,8 in the intermediate risk group,and 11 in the high risk group.Survival analysis showed that the median OS of the three groups was 69 months,34 months,and 13 months(P<0.001).HRCA included a total of 333 NDMM patients,of which 63 were in the low risk group,122 were in the intermediate risk group,and148 were in the high risk group.Survival analysis showed that the median OS of the three groups were 59 months,30 months,and 16 months(P<0.001).In summary,the prognostic model can further stratify NDMM patients in SRCA and HRCA patients.(4)Age:A total of 560NDMM patients with PI and age results were included;365,136,and 59 NDMM patients aged<65 years,65-75 years,and?75 years,respectively.Survival analysis showed that:The median OS of the three groups were 39 months,24 months,and 15 months(P<0.001),suggesting that the older the NDMM patients,the worse the prognosis;a total of 365 NDMM patients were included in the age group<65 years old,of which 200 were low risk Group,112patients were in the intermediate risk group and 53 patients were in the high risk group.Survival analysis showed that the median OS of the three groups was 59 months,30 months,and 16 months(P<0.001).A total of 195 NDMM patients aged?65 years were included,of which 40 were in the low risk group,18 were in the intermediate risk group,and 137 were in the high risk group.Survival analysis showed that the median OS were 58 months,46months,and 16 months(P<0.001).In summary,the prognostic model can further stratify NDMM patients in patients<65 years of age and?65 years of age.Conclusions:1.Age?65 years old,hemoglobin<100g/L,platelet count<100×10~9/L,HRCA are independent adverse prognostic factors that affect OS.2.Prognostic model:low-risk group:0?PI?1 point,median OS is 58m;intermediate-risk group:PI=1.5 points,median OS is 31m;high-risk group:2?PI?3 points,median The OS was 16m,and the risk of death in the high-risk group was three times higher than in the lower-risk group(P<0.001).3.The prognostic model established by combining age,platelet count,hemoglobin and cytogenetic abnormalities has important prognostic value.It can accurately divide NDMM patients into low risk,intermediate risk,and high risk groups according to different prognostic indexes,and is independent of ISS/R-ISS stage,abnormal cytogenetics and age risk stratification system can further accurately stratify NDMM patients.