LAUSR

Central nervous system (CNS) involvement is a rare and aggressive complication of multiple myeloma (MM). We identified 54/4352 MM patients (1.2%), who developed CNS‐MM between 2000 and 2022. A matched‐control group of MM patients without CNS‐MM was used for comparisons. Median age was 63 years. Median time to CNS‐MM was 28 months; 6/54 experienced CNS‐MM at MM diagnosis. Abnormal lactate dehydrogenase (LDH), high‐risk cytogenetics, and extramedullary involvement (EMI), that is, soft tissue plasmacytomas and/or plasma cell leukemia (PCL), were more frequent in CNS‐MM versus controls (p < .05); 13/54 had PCL at CNS‐MM. The majority had leptomeningeal infiltration (LMI) (66%); 26% had CNS‐MM without systemic myeloma; EMI was the strongest predictor for CNS‐MM (OR: 6.3). Median overall survival (OS) of CNS‐MM patients versus controls was 43 months (95% CI: 32–54) versus 60 months (95% CI: 38–82) (p < .001); treatment of CNS‐MM included mainly bortezomib/thalidomide/chemotherapy whereas 20% received novel drugs/immunotherapy combinations; 28 patients underwent cerebrospinal fluid infusions; EMI was the strongest negative predictor for post CNS‐MM OS (p = .005; HR: 2.9). Treatment after 2016 predicted significantly for OS (p = .002; HR: 0.27). Median post CNS‐MM OS was 4 months (95% CI: 2.6–5.4); in patients treated after 2016 median OS was 12 months. In conclusion, we have demonstrated in this large real‐world series that survival of CNS‐MM remains poor; however, there is a positive impact of treatment after 2016, related to the efficacy of modern anti‐myeloma therapy; EMI significantly increases the probability to develop CNS‐MM and the risk of post CNS‐MM death, indicating a potential need for CNS prophylaxis for those patients.