Survival of myeloma patients has greatly improved with the use of autologous stem cell transplantation and novel agents, such as proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies. Compared to bortezomib- and lenalidomide-based regimens alone, the addition of high-dose melphalan followed by autologous transplantation significantly improves progression-free survival, although an overall survival benefit was not observed in all trials. Moreover, follow up of recent trials is still too short to show any difference in survival. In the light of these findings, novel agent-based induction followed by autologous transplantation is considered the standard upfront treatment for eligible patients (level of evidence: 1A). Post-transplant consolidation and maintenance treatment can further improve patient outcome (1A). The availability of several novel agents has led to the development of multiple combination regimens such as salvage treatment options. In this context, the role of salvage autologous transplantation and allotransplant has not been extensively evaluated. In the case of prolonged remission after upfront autologous transplantation, another autologous transplantation at relapse can be considered (2B). Patients who experience early relapse and/or have high-risk features have a poor prognosis and may be considered as candidates for clinical trials that, in young and fit patients, may also include an allograft in combination with novel agents (2B). Ongoing studies are evaluating the role of novel cellular therapies, such as inclusion of antibody-based triplets and quadruplets, and chimeric antigen receptor-T cells. Despite encouraging preliminary results, longer follow up and larger patient numbers are needed before the clinical use of these novel therapies can be widely recommended.

Centre for Haematology Department of Medicine Imperial College London UK

Department of Clinical Hematology Centre Hospitalier Universitaire de Liège Domaine Universitaire du Sart Tilman Liège Belgium

Department of Clinical Therapeutics National and Kapodistrian University of Athens School of Medicine Greece

Department of Hematology Erasmus Medical Center Rotterdam the Netherlands

Department of Hematology VU University Medical Center Amsterdam the Netherlands

Department of Hematooncology University Hospital Ostrava Czech Republic and Faculty of Medicine University of Ostrava Czech Republic

Department of Internal Medicine 2 University Hospital Würzburg Germany

Department of Oncology A O U Città della Salute e della Scienza di Torino and Department of Molecular Biotechnology and Health Sciences University of Torino Italy

Department of Stem cell Transplantation University Medical Center Hamburg Eppendorf Germany

Division of Stem Cell Transplantation and Immunotherapy 2 Medical Department University Hospital Schleswig Holstein Campus Kiel Kiel Germany

INSERM UMR_S 938 Proliferation and Differentiation of Stem Cells Paris AP HP Hôpital Saint Antoine Département d'Hématologie et de Thérapie Cellulaire; Sorbonne Universités UPMC Univ Paris 06 France

Medizinische Klinik Abteilung Innere Medizin 5 Universitätsklinikum Heidelberg und National Centrum für Tumorerkrankungen Heidelberg Germany

Myeloma Unit Division of Hematology University of Torino Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino Italy

Seragnoli Institute of Hematology Bologna University School of Medicine Italy

Tumorzentrum München Germany

Universitätsklinikum Freiburg Medical Department Hematology Oncology and Stem Cell Transplantation Freiburg Germany

Wilhelminen Cancer Research Institute c o Department of Medicine 1 Center of Oncology Hematology and Palliative Care Vienna Austria

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