Multiple myeloma is considered incurable and requires combined and continuous treatments. We present 4 cases of patients with multiple myeloma who received daratumumab after the administration of combined therapy to achieve the best response possible, 3 patients debuted with high-risk disease. In this case series, 100% of patients achieved a strict complete response with undetectable Minimal Residual Disease (MRD) by flow cytometry, after the administration of daratumumab regardless of the scheme used in induction and consolidation, with or without autologous transplantation. After daratumumab, all patients received lenalidomide for at least 6 months with subsequent discontinuation. Follow-up included MRD.