Abstract
Background: Oxidative stress contributes to the initiation and progression of multiple myeloma and can be reflected by various biochemical indicators. However, whether systemic oxidative stress level can serve as a simple and effective alternative for prognostic risk stratification in newly diagnosed multiple myeloma (NDMM) patients remains to be explored and validated in large clinical cohorts. Methods: A retrospective analysis was conducted on 1107 NDMM patients, 774 patients were randomly assigned to the training cohort and 333 to the validation cohort. They were divided into two groups based on the oxidative stress score (OSS), calculated by the weights of systemic oxidative stress indicators. The relationship between systemic oxidative stress levels of multiple myeloma and prognosis were analyzed both in the training and validation cohorts. Results: Constructed by three oxidative stress-related indicators, OSS was associated with significantly shorter overall and progression-free survival in the high OSS group compared to the low OSS group. The 5-year AUC value of the time-dependent ROC for OSS was comparable to that of RISS, and significantly higher than that of the DS staging system. Moreover, patients with high OSS did not benefit significantly from standard combination therapy with IMiDs and PIs over monotherapy in terms of prognosis when compared to the low OSS group (all p < 0.05). Conclusions: OSS was observed to be an independent prognostic factor for overall survival and progression-free survival in patients with NDMM, suggesting systemic oxidative stress could serve as a new approach for accurate prognostic prediction and guiding treatment in multiple myeloma.