Abstract
BACKGROUND: Previous studies mainly focused on renal impairment (RI) at multiple myeloma (MM) diagnosis, with few investigating new-onset RI post-MM diagnosis. This study aims to indicate the incidence, clinical characteristics and predictive value of new-onset RI in MM patients. METHODS: We conducted a multicenter, retrospective cohort study including 1953 newly diagnosed MM patients from West China Hospital from July 1, 2008, to February 30, 2024 and the international MMRF-CoMMpass database. Among them, 1770 patients received novel therapeutic agents including immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) as first-line therapy. RI was defined as serum creatinine higher than 2 mg/dL or impaired creatinine clearance (< 40 mL/min/1.73m(2)). The association between new-onset RI and mortality risk was investigated by Kaplan-Meier analysis and Cox proportional hazard models. RESULTS: Of the cohort, 16.6% developed new-onset RI, with the majority (67.1%) occurring within 2 years post-MM diagnosis. The median overall survival (OS) was significantly shorter in new-onset RI than in those without RI (68 vs. 122 months, p < 0.001). New-onset RI was an independent risk factor for mortality (HR 1.55, 95% CI 1.28-1.88, p < 0.001), and earlier onset of RI was associated with a higher mortality risk. Moreover, patients with recovery of renal function had prolonged OS compared to those without recovery (95 vs. 64.8 months, p = 0.01). Older age, higher stage of the international stage system (ISS) and RI at diagnosis seemed to be risk factors for new-onset RI, while first-line therapy with PIs and IMiDs combinations was associated with a lower risk of RI development (HR 0.69, 95% CI 0.51-0.94, p = 0.017). CONCLUSIONS: In conclusion, the incidence of new-onset RI is high in MM, and is a significant risk factor for mortality, posing a substantial threat to MM patients. Early identification of high-risk patients for new-onset RI and prompt preventive strategies is critical for improving MM prognosis. TRIAL REGISTRATION: This study was registered by the Chinese Clinical Trial Registry (ChiCTR2400081476, https://www.chictr.org.cn).