title: Minimal residual disease after transplantation or lenalidomide-based consolidation in myeloma patients: a prospective analysis.
abstract: We analyzed 50 patients who achieved at least a very good partial response in the RV-MM-EMN-441 study. Patients received consolidation with autologous stem-cell transplantation (ASCT) or cyclophosphamide-lenalidomide-dexamethasone (CRD), followed by Lenalidomide-based maintenance. We assessed minimal residual disease (MRD) by multi-parameter flow cytometry (MFC) and allelic-specific oligonucleotide real-time quantitative polymerase chain reaction (ASO-RQ-PCR) after consolidation, after 3 and 6 courses of maintenance, and thereafter every 6 months until progression. By MFC analysis, 19/50 patients achieved complete response (CR) after consolidation, and 7 additional patients during maintenance. A molecular marker was identified in 25/50 patients, 4/25 achieved molecular-CR after consolidation, and 3 additional patients during maintenance. A lower MRD value by MFC was found in ASCT patients compared with CRD patients (p=0.0134). Tumor burden reduction was different in patients with high-risk vs standard-risk cytogenetics (3.4 vs 5.2, ln-MFC; 3 vs 6 ln-PCR, respectively) and in patients who relapsed vs those who did not (4 vs 5, ln-MFC; 4.4 vs 7.8 ln-PCR). MRD progression anticipated clinical relapse by a median of 9 months while biochemical relapse by a median of 4 months. MRD allows the identification of a low-risk group, independently of response, and a better characterization of the activity of treatments.
authors: Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospeadliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
authors: Stefania
authors: S
authors: Oliva
authors: Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospeadliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
authors: Manuela
authors: M
authors: Gambella
authors: Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospeadliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
authors: Milena
authors: M
authors: Gilestro
authors: Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospeadliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
authors: Vittorio Emanuele
authors: VE
authors: Muccio
authors: Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospeadliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
authors: Francesca
authors: F
authors: Gay
authors: Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy.
authors: Daniela
authors: D
authors: Drandi
authors: Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy.
authors: Simone
authors: S
authors: Ferrero
authors: Division of Nuclear Medicine, University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
authors: Roberto
authors: R
authors: Passera
authors: Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospeadliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
authors: Chiara
authors: C
authors: Pautasso
authors: Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospeadliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
authors: Annalisa
authors: A
authors: Bernardini
authors: Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospeadliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
authors: Mariella
authors: M
authors: Genuardi
authors: Azienda Ospedaliera-Universitaria di Udine, DISM Università di Udine, Udine, Italy.
authors: Francesca
authors: F
authors: Patriarca
authors: Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospeadliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
authors: Elona
authors: E
authors: Saraci
authors: Division of Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, Italy.
authors: Maria Teresa
authors: MT
authors: Petrucci
authors: Ematologia e Centro TMO, Ospedale Centrale Bolzano, Bozen, Italy.
authors: Norbert
authors: N
authors: Pescosta
authors: AO S.Maria di Terni, SC Oncoematologia, Terni, Italy.
authors: Anna Marina
authors: AM
authors: Liberati
authors: UOC Ematologia S.Eugenio ASL RM2 Roma, Rome, Italy.
authors: Tommaso
authors: T
authors: Caravita
authors: Divisione di Ematologia, Azienda Policlinico-OVE, Università di Catania, Catania, Italy.
authors: Concetta
authors: C
authors: Conticello
authors: Department of Haematology, Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
authors: Alberto
authors: A
authors: Rocci
authors: Scientific Direction, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture (Pz), Italy.
authors: Pellegrino
authors: P
authors: Musto
authors: Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospeadliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
authors: Mario
authors: M
authors: Boccadoro
authors: Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospeadliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
authors: Antonio
authors: A
authors: Palumbo
authors: Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospeadliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
authors: Paola
authors: P
authors: Omedè
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D060830:Consolidation Chemotherapy; D018450:Disease Progression; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D018365:Neoplasm, Residual; D011446:Prospective Studies; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014182:Transplantation, Autologous / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D013792:Thalidomide; D000077269:Lenalidomide
keywords: ASO-RQ-PCR; MRD; flow cytometry; myeloma; novel agents