Ultrasensitive detection of circulating multiple myeloma cells by next-generation flow after immunomagnetic enrichment
Abstract
Abstract 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.
Article Details
Authors (32)
Marta Lasa
1Cancer Center Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), Instituto de Investigacion Sanitaria de Navarra (IDISNA), CIBER-ONC CB16/12/00369, Pamplona, Spain
Carmen González
Laura Notarfranchi
1Cancer Center Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), Instituto de Investigacion Sanitaria de Navarra (IDISNA), CIBER-ONC CB16/12/00369, Pamplona, Spain
Anastasiia Zherniakova
1Cancer Center Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), Instituto de Investigacion Sanitaria de Navarra (IDISNA), CIBER-ONC CB16/12/00369, Pamplona, Spain
Diego Alignani
Leire Burgos
12Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), Instituto de Investigacion Sanitaria de Navarra (IDISNA), CIBER-ONC number CB16/12/00369, Pamplona, Spain
María José Calasanz
7Genetics Department, CIMALAB Diagnostics, Clínica Universidad de Navarra, Pamplona, Spain
Paula Rodriguez-Otero
José J. Perez
13Department of Hematology, Hospital Universitario de Salamanca Hematología, Instituto de Investigación Biomédica de Salamanca, CIBER-ONC number CB16/12/00233, Salamanca, Spain
Clara Gomez
5Hospital de Galdakao, Vizcaya, Spain
Veronica Gonzalez de la Calle
4Hospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca, University of Salamanca, CIBERONC CB16/12/00233, Salamanca, Spain
Felipe de Arriba
18Department of Hematology, Hospital Morales Meseguer, IMIB Pascual Parrilla, Universidad de Murcia, Murcia, Spain
Luis Palomera
19Hospital Clínico Universitario Lozano Blesa, Hematology, Zaragoza, Spain
Miguel Angel Alvarez Rivas
8Hospital Universitario Reina Sofia, Cordoba, Spain
Esther Clavero
9Hospital Universitario Virgen De Las Nieves, Granada, Spain
Enrique M. Ocio
From Tel Aviv Sourasky Medical Center (Y.C.C., I.A.), and the Faculty of Medical and Health Sciences, Tel Aviv University (Y.C.C., H.M., I.A.), Tel Aviv, Chaim Sheba Medical Center, Ramat Gan (H.M.), and Hadassah Hebrew University Medical Center, Jerusalem (M.G.) — all in Israel; McGill University and McGill University Health Centre, Montreal (M.S.), and Alberta Health Services, Edmonton (M.P.C.) — all in Canada; Samsung Medical Center, Sungkyunkwan University School of Medicine (K.K.), Seoul St. Mary’s Hospital, Catholic University of Korea (C.-K.M.), and Seoul National University College of Medicine (S.-S.Y.) — all in Seoul, South Korea; Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Sanitaria Valdecilla, Universidad de Cantabria, Santander (E.M.O.), Cancer Center Clínica Universidad de Navarra, Center for Applied Medical Research, Pamplona (P.R.-O.), Institut Català d’Oncologia, Josep Carreras Leukemia Research Institute, and the Hospital Germans Trias i Pujol, Barcelona (A.O.)...
Ana Pilar Gonzalez-Rodriguez
11Hospital Universitario Central de Asturias, Oviedo, Spain
Sunil Lakhwani
Hospital Universitario de Canarias. Universidad de La Laguna., San Cristobal de La Laguna, Tenerife, Spain
Angela Ibañez
13Complejo Hospitalario Universitario de Albacete, Albacete, Spain
Albert Oriol
Institut Català d’Oncologia and Institut Josep Carreras, Hospital Germans Trias i Pujol, Badalona, Spain
Anna Sureda
Institut Català d'Oncologia, Barcelona, Spain
Laura Rosiñol
Hospital Clínic de Barcelona, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona
Christiane Siewert
17Research and Development, Miltenyi Biotec BV & Co KG, Bergisch Gladbach, Germany
Alberto Orfao
Juan-Jose Lahuerta
Instituto de Investigación.Hospital Universitario 12 de Octubre, Madrid, Spain
Joan Bladé
Hospital Clínic i Provincial, Institut de Investicacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
María-Victoria Mateos
Jesus F. San-Miguel
1Cancer Center Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada, Instituto de Investigacion Sanitaria de Navarra, CIBERONC CB16/12/00369 and CB16/12/00489, Pamplona, Spain
Maria-Teresa Cedena
Joaquín Martínez-López
Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre, Complutense University of Madrid, Centro Nacional de Investigaciones Oncológicas, Madrid Institute of Cancer, Madrid
Noemi Puig
Bruno Paiva