Durable CNS remission with elranatamab and intrathecal therapy in relapsed/refractory multiple myeloma

Central nervous system (CNS) involvement in multiple myeloma (MM) is a rare but devastating complication associated with poor prognosis and limited therapeutic options. We report a 73-year-old woman with high-risk IgG kappa MM harboring TP53 [del(17p)] and 13q deletion who developed extramedullary and CNS disease after six prior lines of therapy, including two autologous stem cell transplants, and was triple-class refractory to proteasome inhibitors, immunomodulatory agents, and anti-CD38 monoclonal antibodies. At CNS relapse, cerebrospinal fluid (CSF) cytology demonstrated abundant atypical and binucleated plasma cells, and MRI showed diffuse leptomeningeal enhancement. Elranatamab was initiated using a standard step-up dosing schedule, combined with intrathecal methotrexate and dexamethasone. Within two months, MRI showed complete resolution of leptomeningeal disease and CSF became acellular. Systemic evaluation confirmed a complete response by IMWG criteria, with normalization of serum immunofixation, protein electrophoresis, and free light chains. No cytokine release syndrome or neurotoxicity was observed. The remission has been sustained and remains ongoing at 18 months. This case suggests that BCMA-targeted bispecific antibodies, combined with CNS-directed therapy, may induce deep and durable CNS remission in heavily pretreated MM, and supports further investigation of bispecific antibodies in CNS-involved myeloma.