Biomarkers To Predict Newly Diagnosed Multiple Myeloma Prognosis: Developing And Validating Nomogram Prognostic Models

Part 1.Circulating plasma cells as a biomarker to predict newly diagnosed multiple myeloma prognosis: developing and validating nomogram prognostic modelsObjective: To investigate the prognostic value of circulating plasma cells(CPC)and establish novel nomograms to predict individual progression-free survival(PFS)as well as overall survival(OS)of patients with newly diagnosed multiple myeloma(NDMM).Methods: 191 NDMM patients in Wuhan Union Hospital from 2017.10 to 2020.8were included in the study.The entire cohort was randomly divided into a training(n=130)and a validation cohort(n=61).Univariate and multivariate analyses were performed on the training cohort to establish nomograms for the prediction of survival outcomes,and the nomograms were validated by calibration curves.Results: When the cut-off value was 0.038%,CPC could well distinguish patients with higher tumor burden and lower response rates(P<0.05),and could be used as an independent predictor of PFS and OS.Nomograms predicting PFS and OS were developed according to CPC,lactate dehydrogenase(LDH)and creatinine.The C-index and the area under receiver operating characteristic curves(AUC)of the nomograms showed excellent individually predictive effects in training cohort,validation cohort or entire cohort.Patients with total points of the nomograms ? 60.7for PFS and 75.8 for OS could be defined as low-risk group and the remaining as high-risk group.The 2-year PFS and OS rates of patients in low-risk group was significantly higher than those in high-risk group(p<0.001).Conclusions: CPC is an independent prognostic factor for NDMM patients.The proposed nomograms could provide individualized PFS and OS prediction and risk stratification.Part 2.Developing and validating prognostic nomogram incorporating cytokines for overall survival in patients with newly diagnosed multiple myelomaObjective: The purpose of this study is to explore the relationship between pre-treatment cytokines status and the overall survival,and to establish a prognostic nomogram incorporating cytokines in newly diagnosed multiple myeloma(NDMM)patients.Methods: A total of 121 patients with NDMM from Wuhan Union Hospital were included in our study.Their serum levels of cytokines,including macrophage inflammatory protein 1 alpha(MIP-1?),migration inhibitory factor(MIF),tumor necrosis factor-?(TNF-?),vascular endothelial growth factor-?(VEGF-?),monocyte chemoattractant protein-1(MCP-1)and soluble interleukin IL-17 A,IL-6,IL-21 and IL-10 were assessed before treatment.Based on the results of the multivariate Cox proportional hazards model,we developed a prognostic nomogram.We used the concordance index(C-index)and a calibration curve to measure the predictive performance of the nomogram.Results: Three important variables(lactate dehydrogenase,MIP-1? and creatinine)were incorporated in the nomogram using a multivariate Cox analysis.The 3-year overall survival(OS)rate and progression-free survival(PFS)rate was 83.8% and21.8% in the low-risk group of the nomogram while 17.4% and 8.4% in the high-risk group,respectively.The C-index of the nomogram for OS prediction was 0.80(95%CI: 0.68-0.92)which is superior to the predictive power of Durie-Salmon staging system(C-index=0.58;95% CI: 0.49-0.67),International Staging System(C-index=0.70;95% CI: 0.61-0.79)as well as Revised-International Staging System(C-index=0.71;95% CI: 0.63-0.80).The calibration curve shows that the nomogram accurately predicted the 1-year,2-year,3-year OS of NDMM patients.Conclusion: The established nomogram can provide accurate and individualized OS risk estimation for NDMM patients.