Ultrasensitive detection of circulating multiple myeloma cells by next-generation flow after immunomagnetic enrichment

The continuous improvement in progression-free survival (PFS) of patients with multiple myeloma (MM) raises interest in evaluating peripheral residual disease (PRD) toward more frequent readouts of tumor kinetics while preserving quality of life. We present BloodFlow, a new method combining immunomagnetic enrichment of CD138+ circulating plasma cells in peripheral blood (PB) with next-generation flow (NGF), for the detection of PRD below the 2 × 10-6 NGF threshold. BloodFlow detected PRD in 55 of 644 PB samples (8.5%) from 295 patients. Of note, 52.7% PB samples were positive using BloodFlow and negative by NGF. The lowest PRD detected by BloodFlow was 6 × 10-8. Using bone marrow measurable residual disease (MRD) status as the reference, BloodFlow showed positive and negative predictive values of 95.1% and 76.6%, respectively. Detectable PRD during maintenance or observation predicted dismal PFS and overall survival (2-year rates of 0% and 62%, respectively). BloodFlow surpassed NGF in PB and retained independent prognostic value for PFS in multivariate analysis, including transplant eligibility, the revised International Staging System, complete remission, and MRD status. BloodFlow is the first flow cytometry method that detects tumor cells below the 10-6 threshold, enabling improved minimally invasive monitoring of patients with MM.