AIMS/BACKGROUND: Recent agents have profoundly reshaped the multiple myeloma (MM) landscape. Their real-world impacts need to be assessed over the long term. METHODS: EMMY is a non-interventional, prospective dynamic cohort, conducted in France, since 2017, with 900 patients enrolled each year. Newly diagnosed MM (NDMM) who initiated a treatment from 2017 to 2020 are here described. RESULTS: A total of 1036 non-transplant eligible (NTE) patients (median age: 74.9 years) and 561 patients who received autologous stem cell transplantation (ASCT) (median age: 60.6 years) were enrolled. For ASCT patients, a shift in induction treatment from bortezomib-thalidomide-dexamethasone (VTd) (29.1%) to bortezomib-lenalidomide-dexamethasone (VRd) (55.1%) marked the period. Maintenance treatment with R after ASCT became a standard (75% of patients). In NTE patients, R-based regimens were increasingly used from 29.4% in 2017 (of whom Rd.: 17.0%, VRd: 10.6%) to 73.3% in 2020 (of whom Rd.: 21.8%, VRd: 48.5%). Median progression-free survival (mPFS) was 46.5 months (95% CI: 37.8-50.6) and 18.7 months (95% CI: 16.3-20.8) in ASCT and NTE patients, respectively. In the ASCT group, patients treated with and without R maintenance had a mPFS of 51.8 (95% CI: 44.1-NA) and 29.6 months (95% CI: 21.8-40.9), respectively. In the NTE group, the mPFS was 26.3 (95% CI: 21.9-30.9) and 14.6 months (95% CI: 11.9-17.7) in patients who received an R-based and non-R-based regimen, respectively. The estimated 48-month overall survival rates were 89% (95% CI: 84.5-92.2) and 63% (95% CI: 58.5-67.1) for ASCT and NTE patients, respectively. CONCLUSIONS: The 2017-2020 period was marked by the expansion of R use in both NDMM ASCT and NTE patients.