Bortezomib-melphalan-prednisone (VMP) and continuous lenalidomide-dexamethasone (Rd) represent the standard treatment of transplant-ineligible patients with newly diagnosed multiple myeloma (MM). To date, no randomized trial has compared VMP to Rd, and there is no evidence of the optimal treatment for newly diagnosed MM, particularly in patients with high-risk cytogenetics [del(17p), t(4;14) or t(14;16)]. We pooled together data from patients with newly diagnosed MM treated with VMP or Rd induction followed by lenalidomide maintenance 10 mg (Rd-R) enrolled in the GIMEMA-MM-03-05 and EMN01 trials, to evaluate the efficacy of these treatments in different subgroups of patients, focusing on those with standard- and high-risk cytogenetics. Overall, 474 patients were analyzed (VMP: 257 patients; Rd-R: 217 patients). No differences in progression-free survival (hazard ratio=0.96) and overall survival (hazard ratio=1.08) were observed between standard-risk patients treated with VMP or Rd-R, whereas among the high-risk patients, the probabilities of progression (hazard ratio=0.54) and death (hazard ratio=0.73) were lower in the patients treated with VMP than in those treated with Rd-R. In particular, standard-risk patients >75 years benefited less from VMP than from Rd-R (hazard ratio for progression-free survival=0.96; hazard ratio for overall survival=1.81). In this non-randomized analysis, VMP and Rd-R were equally effective in younger (≤75 years), standard-risk patients, while older ones (>75 years) benefited more from Rd-R. In high-risk patients, VMP improved progression-free survival and overall survival irrespective of age. The source trials are registered at ClinicalTrials.gov (NCT01063179 and NCT01093196).

AO Villa Sofia Cervello Divisione Ematologia 1 UTMO Palermo Italy

Clinica di Ematologia AOU Ospedali Riuniti di Ancona Ancona Italy

Department of Hematooncology University Hospital Ostrava Ostrava Czech Republic

Department of Medicine and Surgery University of Parma Parma Italy

DH Ematologico AO S Pio Benevento Italy

Division of Hematology AOU Policlinico Department of Surgery and Medical Specialties University of Catania Italy

Ematologia CTMO Ospedale A Businco Cagliari Italy

Ematologia IRCCS Casa Sollievo della Sofferenza Hospita San Giovanni Rotondo Italy

Faculty of Medicine University of Ostrava Ostrava Czech Republic

Fondazione Giovanni Paolo 2 Unità Operativa Complessa di Oncoematologia Campobasso Italy

Hematology and Bone Marrow Transplant Unit Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII Bergamo Italy

Hematology Città della Salute e della Scienza Torino Italy

Hematology Fondazione IRCCS Istituto Nazionale Tumori Milan Italy

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

Padova University School of Medicine Hematology and Clinical Immunology Padova Italy

U O C Ematologia AOU G Martino Messina Italy

Udine University Hospital DAME University of Udine Udine Italy

Unit of Clinical Epidemiology AOU Città della Salute e della Scienza di Torino e CPO Piemonte Torino Italy

Unit of Haematology and Stem Cell Transplantation IRCCS CROB Referral Cancer Center of Basilicata Rionero in Vulture Italy

Università degli Studi di Perugia Azienda Ospedaliera Santa Maria Terni Italy

Università del Piemonte Orientale A Avogadro Novara Italy

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ClinicalTrials.gov
NCT01063179, NCT01093196