Central nervous system multiple myeloma: An update for 2026

Central nervous system multiple myeloma (CNS-MM) is a rare yet highly aggressive plasma cell dyscrasia with a poor prognosis. CNS-MM represents a distinct clinical entity characterized by unique diagnostic challenges and therapeutic resistances. Conventional therapies have historically yielded dismal outcomes, with median survival measured in months. Modern diagnosis relies on integrating neurological symptoms, advanced CSF flow cytometry, and high-resolution imaging; however, unified diagnostic criteria remain lacking. In the modern era, multimodal strategies incorporating radiotherapy, BBB-penetrating agents, and immunotherapy have expanded treatment options. Bispecific antibodies and CAR-T therapy demonstrate unprecedented CNS-specific response rates, although data remain limited. This review synthesizes current evidence on CNS-MM epidemiology, risk factors, diagnostics, and therapeutics, highlighting emerging immunotherapeutic approaches and persistent knowledge gaps.