Clinical Characteristics, Treatment Patterns, and Prognosis of Central Nervous System Involvement in Multiple Myeloma: A Multicenter Retrospective Study From China

BACKGROUND: Central nervous system (CNS) involvement is a rare and aggressive complication of multiple myeloma (MM), with limited data on its clinical characteristics and prognosis. This multicenter study characterizes the largest Chinese cohort of MM patients with CNS involvement (MM-CNS) to date. METHODS: We conducted a multicenter retrospective study across nine hematology centers in China (July 2017-June 2024), analyzing clinical records of MM-CNS patients. Data collection encompassed diagnostic parameters, treatment regimens, and survival outcomes. RESULTS: Among 35 identified MM-CNS cases (median age 55 years, range 40-83), CNS manifestations presented at initial MM diagnosis in 31.4% (11/35) versus relapse in 68.6% (24/35), with median latency of 22.8 months from MM diagnosis. Predominant features included IgG subtype (51.4%), λ light chain restriction (54.3%), and high-risk cytogenetics: 1q21 amplification (48.3%), t(4;14) translocation (13.8%), and complex karyotypes of chromosome (35.7%). Diagnostic confirmation combined CSF analysis (protein elevation, plasma cell detection) with neuroimaging (meningeal/parenchymal lesions). Treatments included systemic chemotherapy (88.6%), intrathecal therapy (51.4%), radiotherapy (17.1%), chimeric antigen receptor T-cell (CAR-T) therapy (11.4%), and autologous stem cell transplantation (ASCT) (14.3%). Despite 62.9% overall response rate (36.4% complete remission), 56% relapsed within median 3.1 months (range 1.2-8.4). The median follow-up duration was 19.1 months (range: 0.1-46.8). Median overall survival (OS) at 13.0 months (range 0.1-43.1) with 60% mortality (21/35). CONCLUSIONS: CNS involvement in MM is associated with aggressive disease and poor prognosis. Despite transient responses to multimodal therapies, rapid progression and high mortality persist. Novel strategies are urgently needed to improve outcomes in this high-risk population.