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.
Authors
- Esther Clavero Sanchez
- Enrique M. Ocio (ORCID: https://orcid.org/0000-0002-5765-0085)
- Miguel Angel Alvarez Rivas (ORCID: https://orcid.org/0000-0002-8025-5112)
- Anastasiia Zherniakova (ORCID: https://orcid.org/0000-0001-9260-3025)
- Laura Rosiñol (ORCID: https://orcid.org/0000-0002-2534-9239)
- Felipe de Arriba (ORCID: https://orcid.org/0000-0002-4451-1318)
- Juan José Lahuerta (ORCID: https://orcid.org/0000-0002-3393-9570)
- Jesús F. San Miguel (ORCID: https://orcid.org/0000-0002-9183-4857)
- Leire Burgos (ORCID: https://orcid.org/0000-0003-0998-2496)
- María‐Victoria Mateos (ORCID: https://orcid.org/0000-0003-2390-1218)
- Diego Alignani (ORCID: https://orcid.org/0000-0003-0241-1375)
- Joaquín Martínez‐López (ORCID: https://orcid.org/0000-0001-7908-0063)
- Sunil Lakhwani (ORCID: https://orcid.org/0000-0003-1984-4839)
- María‐Teresa Cedena (ORCID: https://orcid.org/0000-0001-5851-3720)
- Verónica González‐Calle (ORCID: https://orcid.org/0000-0002-5493-6707)
- Noemí Puig (ORCID: https://orcid.org/0000-0001-7535-3861)
- Marta Lasa (ORCID: https://orcid.org/0000-0002-2981-162X)
- Laura Notarfranchi (ORCID: https://orcid.org/0000-0002-4069-1323)
- Albert Oriol (ORCID: https://orcid.org/0000-0001-6804-2221)
- Bruno Paiva (ORCID: https://orcid.org/0000-0003-1977-3815)
- Ana Pilar González (ORCID: https://orcid.org/0000-0002-0565-9133)
- Clara Gómez (ORCID: https://orcid.org/0000-0002-7476-8827)
- Anna Sureda (ORCID: https://orcid.org/0000-0002-1238-6970)
- Luis Palomera (ORCID: https://orcid.org/0000-0003-0359-7191)
- Paula Rodríguez‐Otero (ORCID: https://orcid.org/0000-0001-5236-7785)
- Alberto Órfão (ORCID: https://orcid.org/0000-0002-0007-7230)
- Marı́a José Calasanz (ORCID: https://orcid.org/0000-0002-0374-3008)
- Carmen González (ORCID: https://orcid.org/0009-0001-3074-9229)
- Ángela Ibáñez (ORCID: https://orcid.org/0000-0003-0981-1187)
- Joan Bladé
- Christiane Siewert
- José J. Pérez
Institutions
- University of Parma (IT)
- Universidad de Cantabria (ES)
- Miltenyi Biotec (Germany) (DE)
- Universidad de Salamanca (ES)
- Hospital Universitario de Canarias (ES)
- Josep Carreras Leukaemia Research Institute (ES)
- Hospital General Universitario Morales Meseguer (ES)
- Instituto Maimónides de Investigación Biomédica de Córdoba (ES)
- Hospital Universitario 12 De Octubre (ES)
- Institut Català d'Oncologia (ES)
- Navarre Institute of Health Research (ES)
- Instituto de Investigación Marqués de Valdecilla (ES)
- Hospital Clínic de Barcelona (ES)
- Hospital Universitario Virgen de las Nieves (ES)
- Hospital de Galdakao (ES)
- Hospital Universitario Reina Sofía (ES)
- Russian Research Institute of Hematology and Transfusiology (RU)
- Hospital Universitario Central de Asturias (ES)
- Instituto de Investigación Biomédica de Salamanca (ES)
- Clinica Universidad de Navarra (ES)
- Hospital Clínico Universitario Lozano Blesa (ES)
- Instituto de Investigación Sanitaria Aragón (ES)
- Centro de Investigación del Cáncer (ES)
- Hospital General Universitario de Albacete (ES)
- Complejo Hospitalario Universitario de Albacete (ES)
- Centro de Investigación Biomédica en Red de Cáncer (ES)
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- University of Córdoba (ES)
- Universidad de Murcia (ES)
Publication Details
- Journal
- Blood
- Published
- 2025-05-22
- DOI
- https://doi.org/10.1182/blood.2025029234
- Citations
- 9
- Primary Topic
- Multiple Myeloma Research and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 15.93
Funders
- International Myeloma Foundation
- Pfizer
- AstraZeneca
- Sanofi
- Celgene
- Cancer Research UK
- European Commission
- Associazione Italiana per la Ricerca sul Cancro
- Centro de Investigación Biomédica en Red de Cáncer
- CRIS Cancer Foundation
- Instituto de Salud Carlos III