In newly diagnosed myeloma patients, upfront autologous transplant (ASCT) prolongs progression-free survival 1 (PFS1) compared with chemotherapy plus lenalidomide (CC+R). Salvage ASCT at first relapse may still effectively rescue patients who did not receive upfront ASCT. To evaluate the long-term benefit of upfront ASCT vs CC+R and the impact of salvage ASCT in patients who received upfront CC+R, we conducted a pooled analysis of 2 phase III trials (RV-MM-209 and EMN-441). Primary endpoints were PFS1, progression-free survival 2 (PFS2), overall survival (OS). A total of 268 patients were randomized to 2 courses of melphalan 200 mg/m2 and ASCT (MEL200-ASCT) and 261 to CC+R. Median follow-up was 46 months. MEL200-ASCT significantly improved PFS1 (median: 42 vs 24 months, HR 0.53; P<0.001), PFS2 (4 years: 71 vs 54%, HR 0.53, P<0.001) and OS (4 years: 84 vs 70%, HR 0.51, P<0.001) compared with CC+R. The advantage was noticed in good and bad prognosis patients. Only 53% of patients relapsing from CC+R received ASCT at first relapse. Upfront ASCT significantly reduced the risk of death (HR 0.51; P=0.007) in comparison with salvage ASCT. In conclusion, these data confirm the role of upfront ASCT as the standard approach for all young myeloma patients.

Blood Cancer Research Group Department of Haematooncology Faculty Hospital Ostrava Ostrava Czech Republic

Department of Biomedical Science University of Bari 'Aldo Moro' Medical School Internal Medicine 'G Baccelli' Policlinico Bari Italy

Department of Clinical Haematology Alfred Health Monash University Melbourne Australia

Department of Hematology Azienda Ospedaliera Universitaria di Udine DISM Università di Udine Udine Italy

Department of Hematology Fondazione IRCCS Istituto Nazionale dei Tumori Milano Italy

Department of Oncohematology AO S Maria di Terni Terni Italy

Division of Hematology ASST Grande Ospedale Metropolitano Niguarda Milano Italy

Division of Hematology Azienda Policlinico 'Vittorio Emanuele' University of Catania Catania Italy

Division of Hematology Casa Sollievo della Sofferenza Hospital IRCCS San Giovanni Rotondo Italy

Division of Hematology Department of Cellular Biotechnologies and Hematology Sapienza University of Roma Roma Italy

Faculty of Medicine University of Ostrava Ostrava Czech Republic

Haematology Department Cancer Services Barwon Health Geelong Australia

Hematology and Bone Marrow Transplantation Unit IRCCS San Martino 1st Genova Italy

Hematology Department AOU Ospedali Riuniti di Ancona Ancona Italy

Hematology Department of Clinical Medicine and Surgery AOU Federico 2 Napoli Italy

Hematology Division Chaim Sheba Medical Center Tel Hashomer Israel

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

Scientific Direction IRCCS CROB Referral Cancer Center of Basilicata Rionero in Vulture Potenza Italy

Unit of Clinical Epidemiology Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino and CPO Piemonte Torino Italy

UOC Ematologia S Eugenio ASL RM2 Roma Roma Italy

Zobrazit více v PubMed

Cancer. 2012 Mar 15;118(6):1585-92 PubMed

J Clin Oncol. 2005 Dec 20;23(36):9227-33 PubMed

Blood. 2012 Jul 5;120(1):9-19 PubMed

J Clin Oncol. 2005 May 20;23(15):3412-20 PubMed

Lancet. 2010 Dec 18;376(9758):2075-85 PubMed

J Clin Oncol. 2014 Mar 1;32(7):634-40 PubMed

Blood. 2004 Nov 15;104(10):3052-7 PubMed

Blood. 2011 May 5;117(18):4691-5 PubMed

J Clin Oncol. 2012 Aug 20;30(24):2946-55 PubMed

Blood. 2011 Aug 4;118(5):1239-47 PubMed

Biol Blood Marrow Transplant. 2007 Feb;13(2):183-96 PubMed

J Clin Oncol. 2006 Feb 20;24(6):929-36 PubMed

Blood. 2003 Mar 15;101(6):2144-51 PubMed

N Engl J Med. 2003 May 8;348(19):1875-83 PubMed

Oncologist. 2014 Aug;19(8):829-44 PubMed

Lancet Oncol. 2010 Jan;11(1):29-37 PubMed

Blood. 2015 May 14;125(20):3076-84 PubMed

N Engl J Med. 2016 Aug 25;375(8):754-66 PubMed

Lancet. 2007 Oct 6;370(9594):1209-18 PubMed

N Engl J Med. 2014 Sep 4;371(10):895-905 PubMed

N Engl J Med. 2014 Sep 4;371(10):906-17 PubMed

N Engl J Med. 2008 Aug 28;359(9):906-17 PubMed

Blood. 1998 Nov 1;92(9):3131-6 PubMed

Leukemia. 2015 Dec;29(12):2429-31 PubMed

N Engl J Med. 1996 Jul 11;335(2):91-7 PubMed

Leuk Lymphoma. 2013 Aug;54(8):1658-64 PubMed

Blood Cancer J. 2016 Sep 02;6(9):e466 PubMed

Lancet Oncol. 2015 Dec;16(16):1617-29 PubMed

J Clin Oncol. 2010 Oct 20;28(30):4621-9 PubMed

Blood. 2005 Dec 1;106(12):3755-9 PubMed

Blood. 2008 Mar 1;111(5):2516-20 PubMed

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