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

• BloodFlow detects peripheral residual disease below the 10-6 threshold, which is associated with independent prognostic value for PFS.

• Presence of circulating tumor plasma cells after treatment indicates uncontrolled aggressive tumor regrowth and dissemination.

The continuous improvement in progression-free survival (PFS) of multiple myeloma (MM) patients raises interest in evaluating peripheral residual disease (PRD) towards more frequent readouts of tumor kinetics while preserving quality of life. Here we present BloodFlow, a new method that combines immunomagnetic enrichment of CD138+ circulating plasma cells in peripheral blood (PB) with next-generation flow (NGF), for the detection of PRD below the 2x10-6 NGF threshold. BloodFlow detected PRD in 55/644 (8.5%) PB samples collected from 295 MM patients. Of note, 29/55 (52.7%) PB samples were positive using BloodFlow and negative by NGF. The lowest level of PRD detected by BloodFlow was 6x10-8. Considering patients' minimal residual disease (MRD) status in bone marrow as the reference, BloodFlow showed positive and negative predictive values of 95.1% and 76.6%. Presence of PRD during maintenance or observation predicted dismal progression-free and overall survival (2-year rates of 0% and 62%). 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 in bone marrow. BloodFlow is the first flow cytometry method that detects tumor cells below the 10-6 threshold, which resulted in improved minimally-invasive monitoring of MM patients.