title: Single versus tandem high-dose melphalan followed by autologous blood stem cell transplantation in multiple myeloma: long-term results from the phase III GMMG-HD2 trial.
abstract: The prospective, randomized phase III trial GMMG-HD2 aimed at demonstrating non-inferiority of single (Arm A) versus tandem (Arm B) high-dose melphalan followed by autologous transplantation (HDM/ASCT) with regard to 2-year event-free survival (EFS) in newly-diagnosed multiple myeloma (MM) and included 358 evaluable patients [Intention-to-treat population, (ITT), single/tandem HDM/ASCT: n = 177/181]. After a median follow-up of more than 11 years, non-inferiority of single versus tandem HDM/ASCT was demonstrated using the planned non-inferiority threshold of 15% of the 2-year EFS rate. Neither EFS (P = 0·53) nor overall survival (OS) (P = 0·33) differences were observed in the ITT population. In the tandem arm, 26% (n = 47/181) of patients refused a second HDM/ASCT due to non-medical reasons. A per-protocol (PP) analysis, including patients who received the intervention (single/tandem HDM/ASCT: n = 156/93) and patients who did not receive a second HDM/ASCT due to medical reasons (12%, n = 22/181), did not yield differences in EFS (P = 0·61) or OS (P = 0·16). In the ITT and PP set of the tandem arm, the rates of complete responses increased from first to second HDM/ASCT (both P = 0·04). Ten-year OS for the entire ITT was 34% (95% confidence interval: 29-40%). OS after first relapse was significantly shortened in the tandem arm (P = 0·04). In this study single HDM/ASCT was non-inferior to tandem HDM/ASCT in MM.
authors.affiliation: Department of Internal Medicine V, University Clinic Heidelberg, Heidelberg, Germany.
authors.forename: Elias K
authors.identifier: 0000-0002-6226-1252
authors.initials: EK
authors.lastname: Mai
authors.affiliation: Division of Biostatistics, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Benner
authors.affiliation: Department of Internal Medicine V, University Clinic Heidelberg, Heidelberg, Germany.|Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg, Heidelberg, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Bertsch
authors.affiliation: Medical Clinic and Polyclinic III, University Hospital Bonn, Bonn, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Brossart
authors.affiliation: Department of Internal Medicine III, Klinikum Chemnitz, Chemnitz, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Hänel
authors.affiliation: Department of Internal Medicine II, University Clinic Würzburg, Würzburg, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Kunzmann
authors.affiliation: Department of Medicine I, University Hospital Dresden Carl Gustav Carus, Dresden, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Naumann
authors.affiliation: Department of Haematology and Oncology, Klinikum Baden Baden, Baden Baden, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Neben
authors.affiliation: Department of Internal Medicine V, University Clinic Heidelberg, Heidelberg, Germany.
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Egerer
authors.affiliation: Department of Internal Medicine V, University Clinic Heidelberg, Heidelberg, Germany.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
authors.affiliation: Department of Internal Medicine V, University Clinic Heidelberg, Heidelberg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Hillengass
authors.affiliation: Department of Internal Medicine V, University Clinic Heidelberg, Heidelberg, Germany.
authors.forename: Marc S
authors.identifier: 0000-0003-4181-6922
authors.initials: MS
authors.lastname: Raab
authors.affiliation: Department of Haematology and Oncology, University Clinic Gießen/Marburg, Marburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Neubauer
authors.affiliation: Department of Internal Medicine I, Klinikum Bremen Mitte, Bremen, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Peyn
authors.affiliation: Department of Haematology and Oncology, Evangelische Kliniken Bonn, Bonn, Germany.
authors.forename: Yon-Dschun
authors.initials: YD
authors.lastname: Ko
authors.affiliation: Department of Internal Medicine II, Carl-Thiem Klinikum Cottbus, Cottbus, Germany.
authors.forename: Norma
authors.initials: N
authors.lastname: Peter
authors.affiliation: Department of Internal Medicine I, University Hospital Köln, Köln, Germany.
authors.forename: Christof
authors.initials: C
authors.lastname: Scheid
authors.affiliation: Department of Internal Medicine V, University Clinic Heidelberg, Heidelberg, Germany.|Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg, Heidelberg, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Goldschmidt
mesh_terms: D000328:Adult; D000368:Aged; D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000627:therapeutic use; D008875:Middle Aged; D009101:Multiple Myeloma / Q000401:mortality / Q000628:therapy*; D019653:Myeloablative Agonists / Q000008:administration & dosage / Q000627:therapeutic use; D011446:Prospective Studies; D012074:Remission Induction / Q000379:methods; D016019:Survival Analysis; D014182:Transplantation, Autologous
chemical_list: D019653:Myeloablative Agonists; D008558:Melphalan
keywords: melphalan; myeloma; single transplantation; stem cell transplantation; tandem transplantation