Relapsed/refractory multiple myeloma with extramedullary plasmacytomas successfully rechallenged with humanized...

Multiple myeloma (MM) is a plasma cell malignancy, and extramedullary plasmacytoma (EMP) is associated with an aggressive biology and poor outcomes. B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR-T) therapy has shown substantial activity in relapsed/refractory MM (RRMM); however, evidence in patients with EMP, particularly after prior BCMA CAR-T exposure, remains limited. The present study describes the case of a 38-year-old man with RRMM and extensive cranial EMP who progressed after multiple prior therapies, including proteasome inhibitor- and immunomodulatory drug-based regimens, anti-CD38 therapy, carfilzomib-based therapy and a previous non-humanized BCMA CAR-T product. Due to rapidly progressive disease, the patient received bridging cytoreduction followed by fully humanized BCMA CAR-T therapy (equecabtagene autoleucel). After infusion, serum and urine M-protein levels rapidly declined and the craniofacial mass regressed clinically and radiographically. The patient achieved stringent complete response with durable control of extramedullary disease during follow-up. The present case suggests that fully humanized BCMA CAR-T therapy may remain effective in selected patients with RRMM and EMP, even after prior non-humanized BCMA CAR-T failure. These findings support further investigation into retreatment strategies and post-CAR-T maintenance approaches.