At what point are we on the way to optimally treat multiple myeloma patients over 75 years of age in 2023?

Several novel drugs for multiple myeloma, including monoclonal and bispecific antibodies, immunomodulatory agents, and newer-generation proteasome inhibitors, have been introduced over the last decade. Based on the results of randomized clinical trials, the drugs have been incorporated into current treatment recommendations, with the most substantial changes observed in patients under the age of 75. However, new therapeutic options have been indirectly proposed for patients over 75, despite the lack of conclusive data from randomized prospective trials. This paper outlines the development of myeloma therapy and summarizes the current treatment recommendations for patients over 75 by systematically reviewing the most crucial studies involving this group of individuals, with a focus on evaluating treatment safety and efficacy. Melphalan-prednisone (MP), bortezomib plus MP (VMP), lenalidomide-dexamethasone (Rd), and bortezomib plus Rd (VRd) regimens have evolved over the past few years as therapies of choice for the first-line treatment of these patients. A breakthrough came with daratumumab, which increased response rates, extended median progression-free survival (PFS) and overall survival (OS) in the absence of significantly increased toxicity when added to the above regimens.