Introduction: Multiple myeloma (MM) is a heterogeneous diseases, and the existing risk stratification still has certain limitations. Mayo proposed double-hit MM, a group of subtypes with poor prognosis. This part of the study aims to analyze the clinical characteristics of MM, evaluate the application value of existing staging systems in the real world, and attempt to construct a double-hit-based Nomogram prediction model to identify high-risk MM.

Methods:Clinical data of MM were retrospectively analyzed. The examination and treatment of patients were recorded in detail, and the data of patients who were not newly diagnosed, had no cytogenetic examination, follow-up time of less than 3 months and clinical examinations were seriously missing were excluded. All patients were randomly divided into training group and validation group according to the ratio of 2:1. The predictors were screened by LASSO regression, and the univariate and multivariate survival analysis was performed by Cox proportional hazards regression model.

Results:A total of 443 newly diagnosed MM were included in the analysis, of which 72 cases (16.3%) were double-hit MM. The results of univariate analysis showed that the baseline variables age, ECOG-PS, hemoglobin, albumin, creatinine, serum β2-microglobulin, serum calcium, lactate dehydrogenase, bone marrow plasma cell percentage, ISS, R-ISS, D-S stage system, Del (17p), Gain (1q21) and double-hit cytogenetic abnormality were significantly associated with OS. Multivariate Cox regression analysis showed that the risk of death was associated with 5 independent prognostic variables: age (P<0.001), albumin (P=0.007), β2-microglobulin (P=0.004), lactate dehydrogenase (P<0.001) and Double-hit cytogenetics (P<0.001). Evaluation of the existing staging systems showed that the matching among the three staging systems of D-S, R-ISS and ISS was poor, and all have lower ROC (Receiver Operating Characteristic) area under the curve (AUC), ISS: 0.617(95%CI:0.559-0.675), R-ISS: 0.592(95%CI:0.534-0.650) and D-S: 0.522(95%CI:0.462-0.582), respectively. A new prognostic model was established using the training set data. LASSO and multivariate Cox regression analysis found that age, ISS, lactate dehydrogenase and double-hit cytogenetic abnormality were independent prognostic factors, and a Nomogram prognostic model including the above four variables was established. In the training group and the validation group, the C-index was 0.737 (95%CI: 0.682-0.791) and 0.775 (95% CI: 0.706-0.845), respectively. The calibration plot also showed good agreement between predicted OS and observed OS rates.

Conclusion:The existing staging system still has certain limitations in predicting survival of multiple myeloma. Double-hit multiple myeloma is an independent prognostic factor. The established Nomogram prognostic model based on double-hit cytogenetic abnormalities has good predictive value to OS, which can be used to guide clinical individualized treatment.

This content is only available as a PDF.
2025
Sign in via your Institution