Serum Ferritin Increased the Predictive Value of the International Staging System/Revised International Staging System for Overall Survival

Background Multiple myeloma (MM) is a terminally differentiated plasma cell hematological malignancy. MM remained an incurable disease, accounting for 20% of deaths of hematological malignancies, despite continuous improvements in its treatment. The revised international staging system (RISS) is commonly used in patients with de novo MM, but it has limitations in predicting prognosis. Hence, better prognostic biomarkers and more optimized staging are yet to be explored.

Methods

This retrospective study reviewed 357 patients with MM at our institution from May 2013 to May 2018 and included a total of 302 patients. Differences in serum ferritin levels between patients with relapse/non-relapse and survival/death were assessed. Multivariate-adjusted Cox regression and K-M curve were conducted to analyze the effect of different serum ferritin levels on progression-free survival (PFS) and overall survival (OS) in 7 years. Further, the receiver operating characteristic (ROC) curve analysis was used to evaluate the role of serum ferritin level in increasing the international staging system (ISS) and RISS in prognosis prediction. Multivariate linear regression and binomial logistic regression assessed the association of serum ferritin level with optimal induction therapy response.

Results

The serum ferritin level of patients with MM with recurrence was significantly higher than that of patients without recurrence (P < 0.0001), and the serum ferritin level of patients with all-cause death was significantly higher than that of patients who were still alive during the 7-year follow-up period (P < 0.0001). Smooth curve fitting analysis showed that serum ferritin levels were associated with relapse and death occurrences. The K-M curve analysis indicated that MM patients with high ferritin levels (≥577.47 ng/ml) had shorter PFS (P < 0.0056) and OS (P = 0.0014) than those with ferritin levels of <577.47 ng/ml. Multivariate Cox regression analysis adjusted for potential variables showed that MM patients with high serum ferritin had poor PFS (hazard ratio [HR] = 2.07, 95% confidence interval [CI]: 1.33-3.23, P = 0.0012) and OS (HR = 1.84, 95%CI: 1.08-3.16, P = 0.0258), with independent correlation. The prediction model of ROC analysis based on Cox regression showed that ferritin had a predictive value for PFS (OR_ferritin = 2.158, P_ferritin = 0.0219) and OS (OR_ferritin = 2.2480, P_ferritin = 0.0196). Additionally, the ROC curve showed that serum ferritin could increase the predictive value of ISS and RISS for OS. Multivariate regression analysis showed that serum ferritin levels had no significant independently effect on the optimal response within induction therapy.

Conclusion This retrospective study showed that baseline serum ferritin levels were associated with prognosis in patients with MM, and patients with higher serum ferritin have poorer PFS and OS. Serum ferritin could increase the prediction value of ISS and RISS for OS.

No relevant conflicts of interest to declare.