Journal: American journal of hematology
This publication reviews the emerging role of circulating tumor cells (CTCs) as a liquid biopsy tool in multiple myeloma and related plasma cell disorders.
Key points:
- Biology and disease spectrum: CTCs represent malignant plasma cells that have escaped the bone marrow microenvironment and entered the peripheral blood. They are detectable across the continuum of monoclonal gammopathies—from MGUS and smoldering myeloma through solitary plasmacytoma, symptomatic myeloma, and plasma cell leukemia—providing a real-time view of disease biology and dissemination.
- Technologies: High-sensitivity flow cytometry and next-generation single-cell sequencing have enabled reliable CTC enumeration and detailed molecular characterization. These techniques can capture genomic and transcriptomic features at the single-cell level.
- Prognostic impact: Quantification of CTCs at diagnosis has consistent, independent prognostic value. Even very low CTC levels are associated with inferior survival, supporting CTC burden as a robust risk stratification tool.
- Molecular profiling and clonal evolution: Proof-of-concept approaches such as MinimuMM-seq and SWIFT-seq show that CTC profiling can reproduce canonical myeloma genetic lesions, uncover clonal heterogeneity, and monitor clonal dynamics under treatment, potentially substituting or complementing bone marrow–based assessments.
- Role in response assessment and MRD: Persistent or reemerging CTCs after therapy, particularly when bone marrow MRD is positive, may herald relapse. This positions CTC analysis as a complementary biomarker to bone marrow MRD, with potential utility in longitudinal monitoring.
- Challenges and outlook: The main hurdles are methodological—standardization, optimization of sensitivity, and practical integration into clinical workflows. The authors conclude that with further refinement, CTC analysis could evolve from a surrogate marker into a clinically actionable tool to guide precision therapy in multiple myeloma.