Elevated circulating tumor cells reflect high proliferation and genomic complexity in multiple myeloma

Area of Science:

• Hematology
• Oncology
• Genomics

Background:

• Circulating tumor cells (CTCs) are a prognostic factor in multiple myeloma (MM).
• The biological basis and prognostic significance of high CTC counts in newly diagnosed MM (NDMM) require further elucidation.

Purpose of the Study:

• To characterize genomic and transcriptomic features associated with CTC burden in NDMM.
• To assess the combined prognostic value of CTCs, genomic, and transcriptomic data in NDMM.

Main Methods:

• Analysis of 540 NDMM patients from the CoMMpass dataset with baseline CTC, transcriptomic, and genomic data.
• Validation on an external cohort of 135 NDMM patients using next-generation flow cytometry for CTC enumeration.

Main Results:

• Higher CTC levels correlated with high-risk clinical features and complex genomic alterations (chromothripsis, APOBEC mutagenesis).
• Elevated CTCs were linked to enriched cell cycle/proliferation (PR) genes and reduced immune response signatures.
• CTCs demonstrated prognostic superiority over PR signatures, serving as a surrogate marker.

Conclusions:

• Elevated CTC levels in NDMM reflect aggressive biology and possess significant prognostic value.
• Integrating CTC data into existing classifiers can enhance risk stratification and clinical decision-making for NDMM patients.