Dynamic monitoring of circulating plasma cells in multiple myeloma: A Prospective multicenter study in China Free

The minimally invasive nature of circulating plasma cells (CPCs) measurement provides a valuable alternative for real-time tumor monitoring. A growing body of Western evidence has revealed the prognostic significance of CPCs in patients with multiple myeloma (MM). However, the clinical value of CPCs in Chinese MM patients has not been validated in large-scale prospective cohorts. Furthermore, standardized quantification protocol and applicable cut-off value are currently lacking, hindering robust clinical implementation of CPCs detection in China. In this study, we adopted a standardized eight-color flow cytometry procedure to prospectively evaluate the clinical significance of serial CPCs monitoring in the Chinese myeloma population.

Newly diagnosed MM patients were recruited from eight medical centers between April 1, 2024 and June 20, 2025. Flow cytometry analysis was performed on EDTA-anticoagulated whole peripheral blood samples from each subject. Cells were stained with antibodies against CD38, CD138, CD45, CD56, CD19, CD27, and cytoplasmic kappa and lambda immunoglobulin light chains. CPCs monitoring was conducted every two cycles during induction therapy.

A total of 494 newly diagnosed MM patients were enrolled and underwent baseline CPCs testing. CPCs were detected in 433 patients, yielding a positivity rate of 87.7%. This detection rate reflects an approximately 30% improvement in sensitivity with eight-color flow cytometry over seven-color method. For patients with detectable CPCs, higher baseline CPCs levels significantly correlated with advanced ISS/R-ISS/R2-ISS stage (all P<0.0001) and high-risk cytogenetic abnormalities (HRCAs) (P=0.0008), but not with extramedullary disease (EMD). A modest correlation was observed between CPCs levels and bone marrow plasma cell infiltration (r=0.327). Compared to the baseline CPCs-negative group (n=61), the baseline CPCs-positive group (n=433) had advanced disease staging (ISS-III: 50.6% vs. 31.7%, P=0.006; R-ISS-III: 27.5% vs. 3.6%, P<0.001; R2-ISS-III/IV: 55.4%/16.8% vs. 42.3%/1.9%, P<0.001), elevated tumor burden (BMPC ≥60%: 15% vs. 5%, P=0.035), adverse clinical indicators (β2-MG≥5.5mg/L: 48.6% vs. 26.7%, P=0.001; Albumin<35 g/L 47.3% vs 29.5%, P=0.009; LDH≥ULN: 22.1% vs. 6.6%, P=0.005; Cr ≥177 21.2% vs 9.8%, P=0.038; Hb<100g/L: 65.4% vs. 44.3%, P=0.001), and unfavorable cytogenetic abnormalities (Gain/Amp(1q): 61.2% vs. 34%, P<0.001; R-ISS-defined HRCAs: 31% vs. 13%, P=0.006). 173 patients have completed CPCs monitoring after 2 cycles of induction therapy. Patients with persistent CPCs positivity after treatment (n=25) demonstrated inferior treatment responses compared to those achieving CPCs clearance (n=148) (≥CR: 5% vs. 8.5%; VGPR: 5% vs. 39.7%; ≤PR: 90% vs. 51.8%; P=0.005).

This is the first multicenter prospective study to establish the clinical validity of CPCs in Chinese MM cohort. Initial analysis demonstrates that baseline CPCs significantly correlate with advanced disease stage and HRCAs in newly diagnosed MM. Rapid CPCs clearance after treatment is crucial for achieving superior responses. Defining CPCs threshold and demonstrating the clinical utility of dynamic CPCs monitoring in MM require further validation with extended follow-up data.