(PA-177) Circulating Plasma Cells as an Independent Prognostic Marker in Newly Diagnosed Multiple Myeloma: Clinical Correlation and Immunophenotypic Insights

Circulating plasma cells (CPCs) reflect the dissemination potential of malignant clones in multiple myeloma (MM) and may serve as a surrogate for tumor aggressiveness and microenvironmental independence. However, the prognostic value of baseline CPC levels and their immunophenotypic characteristics relative to bone marrow plasma cells (BMPCs) remains incompletely defined. This study aimed to investigate the clinical and prognostic significance of CPCs at diagnosis and explore their distinct immunophenotypic profile.

Methods:

A total of 212 newly diagnosed MM patients were retrospectively analyzed. Clinical and laboratory parameters, cytogenetic risk, treatment regimens, and outcomes were collected. CPC levels at diagnosis were assessed 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.

Results:

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 (83%) were R-ISS stage II/III. Among patients with detectable circulating plasma cells (CPCs), the median CPC level was 0.16% (IQR: 0.04–0.52%). Regarding treatment, 168 patients (79.2%) received a PIs plus IMiDs-based regimen as first-line therapy, and 70 patients (33%) underwent autologous stem cell transplantation (ASCT).
Patients in the CPC-high group ( > 0.0096%) had significantly higher tumor burden, including more advanced stage, lower platelet and hemoglobin levels, elevated β2-microglobulin and LDH, and more frequent high-risk cytogenetic abnormalities. CPC levels were moderately correlated with PBMC percentage (ρ = 0.51, p < 0.001). CPC-high patients also showed significantly shorter PFS (p = 0.035). In multivariable analysis adjusting for ISS stage, cytogenetics, LDH, and extramedullary disease, increased CPC levels remained independently associated with inferior PFS (HR = 1.60; 95% CI: 1.09–2.33; p = 0.011). Subgroup analysis showed that ASCT significantly mitigated the adverse impact of elevated CPCs. Immunophenotypic comparison revealed significant differences in the expression intensity of CD200, CD28, CD117, and CD81 between CPCs and BMPCs. Moreover, CD28 and CD117 demonstrated lower positivity rates in CPCs. These findings suggest that CPCs may represent a more aggressive subpopulation with reduced microenvironmental dependence, enhanced migratory capacity, and potential treatment resistance, thereby contributing to systemic disease dissemination.

Conclusions:

Baseline CPC 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. CPCs may serve as a valuable biomarker for early risk stratification and therapeutic guidance in MM.