A sequential approach including bortezomib induction, intermediate-dose melphalan, and autologous stem cell transplantation (ASCT), followed by lenalidomide consolidation-maintenance, has been evaluated. Efficacy and safety data have been analyzed on intention-to-treat and results updated. Newly diagnosed myeloma patients 65 to 75 years of age (n = 102) received 4 cycles of bortezomib-pegylated liposomal doxorubicin-dexamethasone, tandem melphalan (100 mg/m(2)) followed by ASCT (MEL100-ASCT), 4 cycles of lenalidomide-prednisone consolidation (LP), and lenalidomide maintenance (L) until disease progression. The complete response (CR) rate was 33% after MEL100-ASCT, 48% after LP and 53% after L maintenance. After a median follow-up of 66 months, median time-to-progression (TTP) was 55 months and median progression-free survival 48 months. Median overall survival (OS) was not reached, 5-year OS was 63%. In CR patients, median TTP was 70 months and 5-year OS was 83%. Median survival from relapse was 28 months. Death related to adverse events (AEs) occurred in 8/102 patients during induction or transplantation. Rate of death related to AEs was higher in patients ≥70 years compared with younger (5/26 vs 3/76, P = .024). Bortezomib-induction followed by ASCT and lenalidomide consolidation-maintenance is a valuable option for elderly myeloma patients, with the greatest benefit in those younger than 70 years of age.