Unveiling the Prognostic Power of Circulating Tumor DNA in Multiple Myeloma: A Systematic Review and Updated...

Circulating tumor DNA (ctDNA) serves as a non-invasive liquid biopsy technique, offering potential utility in the prognostic evaluation of multiple myeloma (MM). In this study, we performed a systematic review and updated meta-analysis to analyze the association between ctDNA and the prognosis of patients diagnosed with MM. A comprehensive literature search was performed across PubMed, Embase, Web of Science, and the Cochrane Library to retrieve relevant literature published up to May 29, 2025, assessing the impact of ctDNA on survival outcomes in patients with MM. The survival outcomes included overall survival (OS), progression-free survival (PFS), and time to progression (TTP). A total of 948 MM patients from 14 studies were included in the analysis. Patients with detectable ctDNA exhibited a significantly increased risk of aggressive disease progression (hazard ratio [HR], 3.21; 95% confidence interval [CI], 1.98-5.18) and reduced OS (HR, 3.97; 95% CI, 2.24-7.04). Subgroup analyses consistently indicated that ctDNA positivity was associated with accelerated disease progression, irrespective of race, disease status, treatment, or ctDNA detection method. In subgroups defined by relapsed or refractory MM (RRMM) and Oceanian or Caucasian race, ctDNA positivity was significantly correlated with poorer OS. However, the associations were not significant in newly diagnosed MM (NDMM) or among Asian patients. Therefore, we conclude that ctDNA is a potential predictor of inferior survival outcomes in MM patients.