Introduction

Circulating tumor plasma cells (CTPCs) reflect the dissemination potential of malignant clones in multiple myeloma (MM) and may serve as a surrogate for tumor aggressiveness and microenvironmental independence. This study investigated the clinical and prognostic relevance of baseline CTPCs and compared their immunophenotype with bone marrow plasma cells (BMPCs).

Methods

A total of 212 newly diagnosed MM patients were retrospectively analyzed. Clinical and laboratory parameters, cytogenetic risk, treatment regimens, and outcomes were collected. CTPC levels were quantified using two-tube, eight-color multiparametric flow cytometry or next-generation flow cytometry. Progression-free survival (PFS) was defined from treatment initiation to progression, death, or last follow-up.

Result

The cohort had a median age of 60 years (range: 52–67); 122 (57.5%) were male. Most patients presented with advanced disease: 155 (73.2%) were ISS stage II/III and 166 (82.6%) were R-ISS stage II/III. Among patients with detectable CTPCs (n=143), the median CTPC level was 0.16% (IQR: 0.04–0.52%). CTPC levels moderately correlated with BMPCs by morphology (r = 0.51, p < 0.001) and flow cytometry (r = 0.50, p < 0.001), and inversely with normal plasma cells (r = -0.28, p < 0.001).

An optimal threshold of 0.01% was established, enabling stratification into CTPC-high and CTPC-low groups. Patients with higher CTPC levels exhibited distinct clinical features, including advanced Durie-Salmon stage III, ISS stage III, R-ISS stage III, elevated β2-microglobulin and LDH levels, lower platelet counts, anemia and a higher frequency of high-risk cytogenetic abnormalities. After a median follow-up of 14.7 months, PFS differed significantly between the two groups (not reached, p = 0.035). Time-dependent ROC analysis demonstrated a consistent, though moderate, discriminatory performance in predicting disease progression (AUC 0.58–0.64 at 6–24 months). Subgroup analysis showed that ASCT significantly mitigated the adverse impact of elevated CTPCs. Immunophenotypic profiling revealed significantly lower expression of CD200, CD28, CD117, and CD81 in CTPCs compared to BMPCs, indicating a more dedifferentiated and migratory phenotype. These findings highlight the utility of baseline CTPCs as a prognostic biomarker reflecting biologically aggressive and microenvironment-independent disease in MM.

Conclusion

Baseline CTPC levels are significantly associated with high-risk disease features and inferior PFS in newly diagnosed MM. Their distinct immunophenotypic profile supports a biologically aggressive and microenvironment-independent phenotype. CTPCs may serve as a valuable biomarker for early risk stratification and therapeutic guidance in MM.

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2025
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