Case Report: Central nervous system relapse treated with elranatamab after prior BCMA and GPRC5D directed therapies in relapsed/refractory multiple myeloma.

Central nervous system (CNS) involvement in multiple myeloma is a rare manifestation associated with aggressive disease biology and a particularly poor prognosis. With the advent of B-cell maturation antigen (BCMA)-directed therapies, evidence regarding their efficacy in CNS-MM remains limited. We report the case of a 70-year-old woman with relapsed/refractory MM who had previously been treated with proteasome inhibitors, immunomodulatory drugs, anti-CD38 monoclonal antibodies, an immune checkpoint inhibitor, an anti-BCMA antibody-drug conjugate, and a GPRC5D-directed bispecific antibody. She developed a late isolated CNS relapse 10 years after the initial diagnosis. Initial treatment for CNS involvement with pomalidomide, cyclophosphamide, and dexamethasone in combination with intrathecal chemotherapy achieved a transient response. Subsequently, treatment with elranatamab, a BCMA-directed bispecific antibody was initiated. After three cycles, cerebrospinal fluid analysis by flow cytometry demonstrated clearance of malignant plasma cells, with sustained negativity thereafter. The patient remains in CNS remission after 12 months of follow-up, with concordant clinical and radiological stability. This case highlights the feasibility and potential clinical activity of elranatamab in CNS-MM in a heavily pretreated patient with prior exposure to both BCMA and GPRC5D directed therapies.