Extramedullary disease (EMD) represents an aggressive form of multiple myeloma (MM) characterized by hematogenous spread of a clone or a subclone of disease able to thrive and grow independently form bone marrow microenvironment. This form of disease has poorer outcome and dismal prognosis. In the last two decades therapeutic armamentarium for treatment of MM is increased and there is a trend toward more prolonged therapy, leading to a better outcome of MM patients. However, the efficacy of the new treatments on patients with EMD is not clear. We retrospectively evaluated patient characteristics and treatment durations in terms of time to next treatment and outcomes in our center from January 1994 until December 2022. A total of 52 patients were evaluable and were investigated. All the patients were diagnosed with multiple myeloma and EMD and received at least one line of therapy during their life. EMD was present at diagnosis or at relapse in 27 (52%) and 25 (48%) patients respectively. Pure extramedullary plasmocytomas were present in 23 (44%), among them seven patients had bone-related plasmocytomas too. Sites involved were: central nervous system (CNS, 7 cases), lung (4 cases), skin (4), lymph nodes (1),pleura (1), eye (1 case), mediastinum (1), liver (1), gallbladder(1), abdomen (1), stomach (1), uterus (1). Bone-related plasmocytomas were present in 29 patients (55%). FISH analysis was evaluable in 33 patients: 16 standard risk, 17 high risk (51,5%). The majority of patients were treated outside controlled clinical trials (39, 75%); 25% of patients (13) have been enrolled in a clinical trial during their life (10, in trials on upfront therapy, 2, in trials on therapy at relapse, one patient in both). On the basis of the year when a patient was exposed to first line therapy, patients were divided in two groups: patients diagnosed and treated from 1994 to 2012 (group A, 11 patients, 21%), and patients diagnosed and treated from 2013 (group B, 41 patients, 79%). Less than a half of patients (24, 46%) are still alive; among them more than 95% were diagnosed and treated after 2012 (group B). 100% (52) of patients were exposed to first line therapy, 81% (42) to second, 73% (38) to third, 46% (24) to fourth, 33% (17) to more than fifth, 9% (3) to more than eight, 3 were allotransplanted (6%) (Table 1). For group A mean and median of lines of therapies were 4.7 and 4 months (range 1-9), for group B were 3.7 and 3 months (range 1-9). Time to next treatment was unfortunately lower from one line of therapy to the next one, particularly in patients belonging to group A where relapses and need of a new treatment occurred more frequently than for patients belonging to group B (introduction of novel agents, maintenance/continuous therapy. Observed cumulative median overall survival (m OS) is 65 months, range 1-202 months. These real-world data show an evolution of EMD patient outcomes in the last two decades. Data are encouraging to design prospective studies including EMD patients for optimal treatment decisions to translate in clinical practice. Table 1 - Patients characteristics 52 EMD At diagnosis 27 (52%) At relapse 25 (48%) Pure EMD 23 (44%) Bone-related plasmacytomas 29 (55%) FISH Standard risk 16 High risk 17 (51.5%) Not evaluable 19 Clinical trials Not included 39 (75%) First line 11(21%) At relapse 2 (4%) First exposition to therapy 1994-2012 11 (21%) >2013 41 (79%) Lines of therapy Median 3 (1-9) First 52 (100%) Second 42 (81%) Third 38 (73%) Fourth 24 (46%) >fifth<eighth 17 (33%) >eighth 3 (9%) Median OS 65 (range 1-202 months)