Development of a Clinical Risk Stratification for Patients with Newly Diagnosed Multiple Myeloma
Authors: Mao Xuehan , Xu Yan , Yan Yuting , Liu Jiahui , Fan Huishou , Sui Weiwei , Deng Shuhui , Li Zengjun , Qiu Lugui , An Gang 
Published: November 2019

Background
The overall survival(OS) of patients with newly diagnosed multiple myeloma(NDMM) shows wide heterogeneity because of the many influence from patient status, disease biology and therapy options. We therefore developed a comprehensive clinical risk stratification for NDMM patients, integrating patients-related and disease-related risk factors, as well as indicators for immuno-microenvironment in the era of novel agents.
Methods
828 cases were enrolled in our study. Clinical and cytogenetic features were described, and OS was calculated. High-risk aberrations (HRA) was defined as 1q21 amplification, del(17p), and t(4;14)/t(14;16) detected by FISH. Anemia was defined as hemoglobin level<100 g/L; decreased ratio of absolute lymphocyte to monocyte counts (ALC/AMC) was defined as less than 2.95(the cut-off of ALC/AMC was calculated according to the ROC curve as well as AUC value); renal dysfunction refers to serum creatinine ≥2mg/dl; elevated LDH was evaluated as serum LDH>247 U/L; HRA number were calculated by the accumulative occurrence of 1q21 gain, del(17p) and t(4;14)/t(14;16).
Results
In the entire cohort, incidence of 0-3 HRA was 39.6%(249/629), 42.0%(264/629), 17.0%(107/629), and 1.4%(9 /629), respectively. Factors included in the univariate analysis for OS were: age (>65 vs.≤65 years old), hemoglobin level (<100 vs ≥100 g/L), ALC/AMC level (<2.95 vs ≥2.95), LDH elevation (>247 vs.≤247 U/L), renal dysfunction (serum creatinine ≥2 vs.<2 mg/dl), ISS stage (ISS III vs. ISS I/II stage), HRA number (2 vs 1 vs 0). Variables with a p-value<0.05 in univariate analysis were entered into the multivariate Cox proportional hazards model. According to the Cox analysis, age>65 years old (HR=1.58, p=0.003), ALC/AMC<2.95 (HR=1.39 ,p=0.04), elevated LDH>247 U/L (HR=1.53 ,p=0.017), one HRA (vs. 0 HRA, HR=1.59, p=0.004), two HRA (vs. 0 HRA, HR=2.66, p=0.000) and ISS stage III (vs. ISS stage I/II, HR=1.74 ,p=0.011) turned out be independent risk factors(Table1). Therefore, 1 or 2 point was assigned to each factor above according to their HR value, and a risk model was derived(Table2). Comparing with the low-risk category, we observed a worse survival in intermediate-risk (HR=2.47, 95%CI 1.82-3.36, p=0.000) and high-risk category (HR=4.68, 95%CI 3.05-7.19, p=0.000). The median overall survival for the three risk group was 101.6(95%CI, 81.09-122.11), 46.8(95%CI, 39.22-54.38) and 27.7(95%CI, 20.42-34.98)(p value was 3.52*10-9 for int risk vs. low risk; p value was 7.99*10-16 for int risk vs. low risk)(Fig1). Moreover, the risk model remained its predictive power in subgroup-analysis according to R-ISS, exposure to novel agents, and transplantation or not.
Conclusion
We developed a comprehensive clinical risk model for overall survival consisting both patients- and disease biology-related factors. This risk model might be effective in risk stratification and treatment guidance for NDMM patients.
Keywords: Multiple myeloma, Risk stratification, Survival

Disclosures
No relevant conflicts of interest to declare.