title: Long-term results of the GIMEMA VEL-03-096 trial in MM patients receiving VTD consolidation after ASCT: MRD kinetics' impact on survival.
abstract: Polymerase chain reaction (PCR)-based minimal residual disease (MRD) analysis is a useful prognostic tool in multiple myeloma (MM), although its long-term impact still needs to be addressed. This report presents the updated results of the GIMEMA-VEL-03-096 trial. Thirty-nine MM patients receiving bortezomib-thalidomide-dexamethasone after autologous transplantation were monitored for MRD by both nested and real-time quantitative-PCR until relapse. Our data confirm the strong impact of MRD on survival: overall survival was 72% at 8 years median follow-up for patients in major MRD response versus 48% for those experiencing MRD persistence (P=0.041). In addition, MRD kinetics resulted predictive for relapse: indeed median remission duration was not reached for patients in major MRD response, 38 months for those experiencing MRD reappearance and 9 months for patients with MRD persistence (P<0.001). Moreover: (1) 26 patients achieving major MRD response (67%) benefit of excellent disease control (median TNT: 42 months); (2) MRD reappearance heralds relapse, with a TNT comparable to that of MRD persistence (9 versus 10 months, P=0.706); (3) the median lag between MRD reappearance and need for salvage treatment is 9 months. These results suggest the usefulness of a long-term MRD monitoring in MM patients and the need for maintenance or pre-emptive treatments ensuring durable responses.
authors.affiliation: Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Ferrero
authors.affiliation: Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Ladetto
authors.affiliation: Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Drandi
authors.affiliation: 1] Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy [2] GIMEMA Italian Myeloma Network, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Cavallo
authors.affiliation: Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Genuardi
authors.affiliation: Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Urbano
authors.affiliation: Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Caltagirone
authors.affiliation: GIMEMA Italian Myeloma Network, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Grasso
authors.affiliation: GIMEMA Italian Myeloma Network, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Rossini
authors.affiliation: GIMEMA Italian Myeloma Network, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Guglielmelli
authors.affiliation: GIMEMA Italian Myeloma Network, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Cangialosi
authors.affiliation: GIMEMA Italian Myeloma Network, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Liberati
authors.affiliation: GIMEMA Italian Myeloma Network, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Callea
authors.affiliation: GIMEMA Italian Myeloma Network, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Carovita
authors.affiliation: GIMEMA Italian Myeloma Network, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Crippa
authors.affiliation: GIMEMA Italian Myeloma Network, Italy.
authors.forename: L
authors.initials: L
authors.lastname: De Rosa
authors.affiliation: GIMEMA Italian Myeloma Network, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Pisani
authors.affiliation: GIMEMA Italian Myeloma Network, Italy.
authors.forename: A P
authors.initials: AP
authors.lastname: Falcone
authors.affiliation: GIMEMA Italian Myeloma Network, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Pregno
authors.affiliation: 1] Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy [2] GIMEMA Italian Myeloma Network, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Oliva
authors.affiliation: GIMEMA Italian Myeloma Network, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Terragna
authors.affiliation: GIMEMA Italian Myeloma Network, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Musto
authors.affiliation: Division of Nuclear Medicine, Città della Salute e della Scienza, University of Torino, Torino, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Passera
authors.affiliation: 1] Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy [2] GIMEMA Italian Myeloma Network, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Boccadoro
authors.affiliation: 1] Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy [2] GIMEMA Italian Myeloma Network, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Palumbo
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction; D011719:Pyrazines / Q000008:administration & dosage; D012008:Recurrence; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage; D014182:Transplantation, Autologous
chemical_list: D001897:Boronic Acids; D007143:Immunoglobulin Heavy Chains; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone