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.

• MeSH
• Administration, Oral MeSH
• Transplantation, Autologous MeSH
• Adult MeSH
• Clinical Trials, Phase III as Topic MeSH
• Lenalidomide MeSH
• Middle Aged MeSH
• Humans MeSH
• Multiple Myeloma mortality   therapy   MeSH
• Aged MeSH
• Thalidomide analogs & derivatives   therapeutic use   MeSH
• Stem Cell Transplantation * MeSH
• Salvage Therapy MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH
• Names of Substances
• Lenalidomide MeSH
• Thalidomide MeSH

This follow-up extension of a randomised phase II study assessed differences in long-term outcomes between bortezomib-thalidomide-dexamethasone (VTD) and VTD-cyclophosphamide (VTDC) induction therapy in multiple myeloma. Newly diagnosed patients (n = 98) were randomised 1:1 to intravenous bortezomib (1·3 mg/m(2); days 1, 4, 8, 11), thalidomide (100 mg; days 1-21), and dexamethasone (40 mg; days 1-4, 9-12), with/without cyclophosphamide (400 mg/m(2); days 1, 8), for four 21-day cycles before stem-cell mobilisation/transplantation. After a median follow-up of 64·8 months, median time-to-next therapy was 51·8 and 47·9 months with VTD and VTDC, respectively. Type of subsequent therapy was similar in both arms. After adjusting for asymmetric censoring, median time to progression was not significantly different between VTD and VTDC [35·7 vs. 34·5 months; Hazard ratio (HR) 1·26, 95% confidence interval: 0·76-2·09; P = 0·370]. Five-year survival was 69·1% and 65·3% with VTD and VTDC, respectively. When analysed by minimal residual disease (MRD) status, overall survival was longer in MRD-negative versus MRD-positive patients with bone marrow-confirmed complete response (HR 3·66, P = 0·0318). VTD induction followed by transplantation provides long-term disease control and, consistent with the primary analysis, there is no additional benefit from adding cyclophosphamide. This study was registered at ClinicalTrials.gov (NCT00531453).

• Keywords
• minimal residual disease, multiple myeloma, transplantation,
• MeSH
• Autografts MeSH
• Bortezomib administration & dosage   MeSH
• Cyclophosphamide administration & dosage   MeSH
• Dexamethasone administration & dosage   MeSH
• Adult MeSH
• Induction Chemotherapy * MeSH
• Middle Aged MeSH
• Humans MeSH
• Survival Rate MeSH
• Multiple Myeloma mortality   therapy   MeSH
• Follow-Up Studies MeSH
• Disease-Free Survival MeSH
• Antineoplastic Combined Chemotherapy Protocols administration & dosage   MeSH
• Aged MeSH
• Thalidomide administration & dosage   MeSH
• Stem Cell Transplantation * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase II MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Names of Substances
• Bortezomib MeSH
• Cyclophosphamide MeSH
• Dexamethasone MeSH
• Thalidomide MeSH