Simple SummaryAbout 35% of patients with multiple myeloma are ≥75 years old at diagnosis, and their treatment should be individualized according to their fragility score. Fragility assessment scales include the International Myeloma Working Group Palumbo Fragility Scale, the Revised Initial Myeloma Comorbidity Index, and the Mayo score. However, they are time-consuming, but more importantly, there are no convincing data from a real world experience supporting their usefulness in everyday clinical practice. Patients with multiple myeloma over 75 years of age are instantly classified as intermediate fit or frail. These patients should be offered non-intensive treatment in reduced doses or palliative care. In the prospective observational, multicenter study, we showed that most patients over 75 years of age qualified for treatment are safely treated with three-drug regimens regardless of their fragility categorization. Current fragility scores for patients with MM over 75 years old have limited value in daily practice.AbstractFragility scales are intended to help in therapeutic decisions. Here, we asked if the fragility assessment in MM patients ≥ 75 years old qualified for treatment by the local physician correlates with the choice of treatment: a two- or three-drug regimens. Between 7/2018 and 12/2019, we prospectively enrolled 197 MM patients at the start of treatment from the 13 Polish Myeloma Group centers. The data to assess fragility were prospectively collected, but centrally assessed fragility was not disclosed to the local center. The activity of daily living (ADL) could be assessed in 192 (97.5%) and was independent in 158 (80.2%), moderately impaired in 23 (11.7%), and 11 (5.6%) in completely dependent. Patients with more than three comorbidities made up 26.9% (53 patients). Thus, according to the Palumbo calculator, 43 patients were in the intermediate fitness group (21.8%), and the rest belonged to the frailty group (153, 77.7%). Overall, 79.7% of patients (157) received three-drug regimens and 20.3% (40) received two-drug regimens. In each ECOG group, more than three out of four patients received three-drug regimens. According to the ADL scale, 82.3% of the independent 65.2% of moderately impaired, and 81.8% of the dependent received three-drug regimens. Out of 53 patients with at least four comorbidities, 71.7% received three-drug regimens, and the rest received two-drug regimens. Thirty-four patients from the intermediate fit group (79.0%), and 123 (79.9%) from the frail group received three-drug regimens. Early mortality occurred in 25 patients (12.7%). No one discontinued treatment due to toxicity. To conclude, MM patients over 75 are mainly treated with triple-drug regimens, not only in reduced doses, regardless of their frailty scores. However, the absence of prospective fragility assessment did not negatively affect early mortality and the number of treatment discontinuations, which brings into question the clinical utility of current fragility scales in everyday practice.