The standard treatment for patients with newly diagnosed multiple myeloma (NDMM) is a combination of melphalan, prednisone, and thalidomide (MPT). The phase IIITMM-020/IFM 07 01 trial compared the efficacy and safety of combining lenalidomide and low-dose dexamethasone (Rd) with MPT. The study included 1,623 patients ineligible for stem-cell transplantation, due to age or other factors, who were randomly assigned to three treatment groups: continuous Rd until disease progression, Rd for 72 weeks, or MPT for 72 weeks. Patients treated with continuous Rd were less likely (28%) to experience disease progression or death than those patients treated with MPT. The safety profiles of the two treatment regimens were similar, although patients treated with Rd showed fewer secondary haematological malignancies than those treated with MPT.