title: Prognostic value of deep sequencing method for minimal residual disease detection in multiple myeloma.
abstract: We assessed the prognostic value of minimal residual disease (MRD) detection in multiple myeloma (MM) patients using a sequencing-based platform in bone marrow samples from 133 MM patients in at least very good partial response (VGPR) after front-line therapy. Deep sequencing was carried out in patients in whom a high-frequency myeloma clone was identified and MRD was assessed using the IGH-VDJH, IGH-DJH, and IGK assays. The results were contrasted with those of multiparametric flow cytometry (MFC) and allele-specific oligonucleotide polymerase chain reaction (ASO-PCR). The applicability of deep sequencing was 91%. Concordance between sequencing and MFC and ASO-PCR was 83% and 85%, respectively. Patients who were MRD(-) by sequencing had a significantly longer time to tumor progression (TTP) (median 80 vs 31 months; P < .0001) and overall survival (median not reached vs 81 months; P = .02), compared with patients who were MRD(+). When stratifying patients by different levels of MRD, the respective TTP medians were: MRD ≥10(-3) 27 months, MRD 10(-3) to 10(-5) 48 months, and MRD <10(-5) 80 months (P = .003 to .0001). Ninety-two percent of VGPR patients were MRD(+). In complete response patients, the TTP remained significantly longer for MRD(-) compared with MRD(+) patients (131 vs 35 months; P = .0009).
authors.affiliation: Hospital Universitario 12 de Octubre, Madrid, Spain;
authors.forename: Joaquin
authors.initials: J
authors.lastname: Martinez-Lopez
authors.affiliation: Hospital Universitario 12 de Octubre, Madrid, Spain;
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Lahuerta
authors.affiliation: Sequenta, Inc., San Francisco, CA;
authors.forename: François
authors.initials: F
authors.lastname: Pepin
authors.affiliation: Hospital Universitario de Salamanca-IBSAL, IBMCC-CSIC, Salamanca, Spain;
authors.forename: Marcos
authors.initials: M
authors.lastname: González
authors.affiliation: Hospital Universitario 12 de Octubre, Madrid, Spain;
authors.forename: Santiago
authors.initials: S
authors.lastname: Barrio
authors.affiliation: Hospital Universitario 12 de Octubre, Madrid, Spain;
authors.forename: Rosa
authors.initials: R
authors.lastname: Ayala
authors.affiliation: Hospital Universitario de Salamanca-IBSAL, IBMCC-CSIC, Salamanca, Spain;
authors.forename: Noemí
authors.initials: N
authors.lastname: Puig
authors.affiliation: Hospital Universitario 12 de Octubre, Madrid, Spain;
authors.forename: María A
authors.initials: MA
authors.lastname: Montalban
authors.affiliation: Clínica Universitaria de Navarra, Centro de Investigación Médica Aplicada (CIMA), Pamplona, Spain;
authors.forename: Bruno
authors.initials: B
authors.lastname: Paiva
authors.affiliation: Sequenta, Inc., San Francisco, CA;
authors.forename: Li
authors.initials: L
authors.lastname: Weng
authors.affiliation: Hospital Universitario de Salamanca-IBSAL, IBMCC-CSIC, Salamanca, Spain;
authors.forename: Cristina
authors.initials: C
authors.lastname: Jiménez
authors.affiliation: Hospital Universitario 12 de Octubre, Madrid, Spain;
authors.forename: María
authors.initials: M
authors.lastname: Sopena
authors.affiliation: Sequenta, Inc., San Francisco, CA;
authors.forename: Martin
authors.initials: M
authors.lastname: Moorhead
authors.affiliation: Hospital Universitario 12 de Octubre, Madrid, Spain;
authors.forename: Teresa
authors.initials: T
authors.lastname: Cedena
authors.affiliation: Hospital Universitario 12 de Octubre, Madrid, Spain;
authors.forename: Immaculada
authors.initials: I
authors.lastname: Rapado
authors.affiliation: Hospital Universitario de Salamanca-IBSAL, IBMCC-CSIC, Salamanca, Spain;
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Mateos
authors.affiliation: Hospital Clínic i Provincial de Barcelona, Institut d'Investigacions Biomédiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain;
authors.forename: Laura
authors.initials: L
authors.lastname: Rosiñol
authors.affiliation: Hospital Germans Trias i Pujol, Barcelona, Spain;
authors.forename: Albert
authors.initials: A
authors.lastname: Oriol
authors.affiliation: Hospital Ramón y Cajal, Madrid, Spain; and.
authors.forename: María J
authors.initials: MJ
authors.lastname: Blanchard
authors.affiliation: Hospital Clínico de Madrid, Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Martínez
authors.affiliation: Hospital Clínic i Provincial de Barcelona, Institut d'Investigacions Biomédiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain;
authors.forename: Joan
authors.initials: J
authors.lastname: Bladé
authors.affiliation: Clínica Universitaria de Navarra, Centro de Investigación Médica Aplicada (CIMA), Pamplona, Spain;
authors.forename: Jesús
authors.initials: J
authors.lastname: San Miguel
authors.affiliation: Sequenta, Inc., San Francisco, CA;
authors.forename: Malek
authors.initials: M
authors.lastname: Faham
authors.affiliation: Hospital Universitario de Salamanca-IBSAL, IBMCC-CSIC, Salamanca, Spain;
authors.forename: Ramón
authors.initials: R
authors.lastname: García-Sanz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D018365:Neoplasm, Residual; D011379:Prognosis