Minimally Invasive Assessment of Peripheral Residual Disease During Maintenance or Observation in Transplant-Eligible Patients With Multiple Myeloma
Abstract
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. In multiple myeloma (MM), measurable residual disease (MRD) is assessed in bone marrow (BM). However, less invasive evaluation of peripheral residual disease (PRD) in blood could be advantageous and less cumbersome. We investigated the prognostic value of PRD monitoring after 24 cycles of maintenance in 138 transplant-eligible patients with MM enrolled in the GEM2012MENOS65/GEM2014MAIN clinical trials. PRD was assessed using next-generation flow (NGF) and mass spectrometry (MS). Positive PRD by NGF in 16/138 (11.5%) patients was associated with a 13-fold increased risk of progression and/or death; median progression-free survival (PFS) and overall survival (OS) were 2.5 and 47 months, respectively. Considering patients' MRD status in BM as the reference, PRD detection using NGF showed positive and negative predictive values of 100% and 73%, respectively. Presence of PRD helped identifying patients at risk of imminent progression among those with positive MRD in BM. Patients with undetectable PRD according to both NGF and MS showed 2-year PFS and OS rates of 97% and 100%, respectively. In multivariate analyses including the Revised International Staging System and the complete remission status, only MRD in BM and PRD by NGF showed independent prognostic value for PFS. This study supports the use of less invasive PRD monitoring during maintenance or observation in transplant-eligible patients with MM.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (87)
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
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
Cristina Agullo
2Hospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), University of Salamanca, Salamanca, Spain
Carmen González
Sergio Castro
2Hospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), University of Salamanca, Salamanca, Spain
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
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
Camila Guerrero
CIMA, Pamplona, Spain
María José Calasanz
7Genetics Department, CIMALAB Diagnostics, Clínica Universidad de Navarra, Pamplona, Spain
Juan Flores-Montero
2University of Salamanca, Clinical and Translational Research Program, Cancer Research Center (IBMCC-CSIC/USAL-IBSAL), Salamanca, Spain
Albert Oriol
Institut Català d’Oncologia and Institut Josep Carreras, Hospital Germans Trias i Pujol, Badalona, Spain
Joan Bargay
Hospital Universitario Son LLatzer, Instituto de Investigación Sanitaria Illes Balears (IdISBa),, Palma de Mallorca, Spain
Rafael Ríos
7Hospital Universitario Puerta de Hierro, Majadahonda, Spain
Valentin Cabañas
21Department of Hematology, IMIB Virgen de la Arrixaca University Hospital, University of Murcia, Murcia, Spain
Carmen Cabrera
Hospital San Pedro de Alcántara, Cáceres, Spain
Rafael Martínez-Martínez
13Hematology Department, Hospital Clínico San Carlos, Madrid, Spain
Cristina Encinas
14Department of Hematology, Hospital General Universitario Gregorio Marañón, liSGM, Madrid, Spain
Felipe de Arriba
18Department of Hematology, Hospital Morales Meseguer, IMIB Pascual Parrilla, Universidad de Murcia, Murcia, Spain
Miguel-Teodoro Hernandez
Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain
Luis Palomera
19Hospital Clínico Universitario Lozano Blesa, Hematology, Zaragoza, Spain
Alberto Orfao
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
María-Victoria Mateos
Jesus San-Miguel
Juan José Lahuerta
1Hematology Department, Instituto de Investigación Hospital Universitario 12 de Octubre, Madrid, Spain
Laura Rosiñol
Hospital Clínic de Barcelona, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona
Joan Bladé
Hospital Clínic i Provincial, Institut de Investicacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
María Teresa Cedena
22Hospital Universitario 12 de Octubre, Instituto de Investigación (i+12), Madrid, Spain
Noemi Puig
Bruno Paiva
María Casanova
Carmen Couto
33Hospital Nuestra Señora de Valme, Sevilla, Spain
Estrella Carrillo
Esther Gonzalez
Hospital Universitario de Cabueñes, Gijon, Spain
Ana Pilar Gonzalez
6Hospital Universitario Central de Asturias, Oviedo, Spain
Antonia Sampol
Alexia Suárez
Carmen Montes
46Hospital Virgen de la Concha, Zamora, Spain
Mª del Carmen Calle
Luís Felipe Casado
Dunia De Miguel
23Hospital Universitario de Guadalajara, Hematology, Guadalajara, Spain
Angela Ibañez
13Complejo Hospitalario Universitario de Albacete, Albacete, Spain
Jorge Labrador
1Hospital Universitario de Burgos, Burgos, Spain
Aránzazu García
Fernando Escalante
22Department of Hematology, Complejo Hospitalario de León, León, Spain
Carlos Aguilar
Lourdes Escoda
Ana María Sureda
Cristina Motlló
15Corporacio Sanitària Parc Tauli, Institut d'Investigacio i Innovacio Parc Tauli I3PT, Universitat Autònoma de Barcelona, Sabadell, Barcelona, Spain
Yolanda González
Eugenia Monreal
Juan Alfonso Soler
8Hospital Universitario Parc Taulí, Barcelona, Spain
Miquel Granell
Elena Cabezudo
13Hospital Moises Broggi - ICO, St Joan Despi, Barcelona, Spain
Josep Mª Martí
Antonio Garcia
3Hospital Arnau de Vilanova, Lleida, Spain
Mercedes Gironella
Ana Dios
José Ángel Méndez
Marta Sonia Gonzalez
Department of Hematology, Complejo Hospitalario Universitario de Santiago de Compostela, Servizio Galego de Saúde, Compostela, Spain
Mª José Nájera
Francisco Javier Peñalver
Pilar Bravo
José Ángel Hernández
Jaime Pérez de Oteyza
Rebeca Iglesias del Barrio
Ana López de la Guía
Adrian Alegre
11University Hospital La Princesa & University Hospital Quiron Salud, Autónoma University, Madrid, Spain
Isabel Krsnik
Elena Ruiz
2Cancer Center Clinica Universidad de Navarra, Center for Applied Medical Research, Department of Hematology, Navarra, Spain
Mª Jesús Blanchard
Belén Íñigo
Eugenio Giménez
8Hospital Universitario Infanta Sofía, Madrid, Spain
Rosalía Riaza
Elena Prieto
Marta Romera
18Hospital General Universitario Santa Lucia, Cartagena, Spain
Jose Mª Moraleda
Felipe Prosper
Jose Mª Arguiñano
María Puente
Xabier Gutiérrez
8Hospital Universitario de Alava, Vitoria, Spain
Ana Isabel Teruel
Paz Rivas
Isidro Jarque
Angel Fernandez
UT MD Anderson Cancer Center, Houston, TX
Amparo Santamaría
Carmen Martínez