Circulating Tumor and Immune Cells for Minimally Invasive Risk Stratification of Smoldering Multiple Myeloma

Area of Science:

• Hematology
• Oncology
• Immunology

Background:

• Optimal risk stratification is crucial for early intervention in smoldering multiple myeloma (SMM) to prevent undertreatment or overtreatment.
• Current models may not fully capture progression risk, necessitating improved prognostic tools.

Purpose of the Study:

• To evaluate the utility of circulating tumor cells (CTCs) and peripheral blood immune biomarkers for risk stratification in SMM.
• To determine if these markers can improve upon the existing International Myeloma Working Group 20/2/20 model.

Main Methods:

• A prospective study of 150 SMM patients with serial assessment of CTCs and immune cells in peripheral blood every 6 months for 3 years.
• Analysis included baseline CTC percentage, bone marrow plasma cells (PCs), and immune cell subsets (monocytes, NK cells, T cells).

Main Results:

• Higher baseline CTCs (>0.015%) were associated with significantly shorter time-to-progression (17 months vs. not reached).
• Bone marrow plasma cells (>20%) lacked prognostic value in multivariate analysis including CTCs and other factors.
• A combined model incorporating CTCs and an immune risk score stratified patients into distinct risk groups with varying 2-year progression rates (0% to 73%).

Conclusions:

• Circulating tumor cells (CTCs) are superior to bone marrow plasma cells (PCs) for assessing tumor burden in SMM.
• Integrating CTCs and immune biomarkers provides a more accurate, minimally invasive method for SMM risk stratification.
• Further studies are needed to establish consensus CTC cutoffs for clinical application.