A Case Report Supporting the Use of Teclistamab in Multiple Myeloma With CNS Involvement

Central nervous system involvement in multiple myeloma (MM-CNS) is a condition with poor prognosis and no clear treatment options. Standard regimens, including proteasome inhibitors (PIs) and immunomodulatory (IMiD) agents, provide minimal benefit in this setting, highlighting the need for novel therapies. Teclistamab, a bispecific T-cell engager (BiTE) targeting B-cell maturation agent (BCMA) and CD3, has demonstrated robust systemic activity in heavily pretreated MM but its role in CNS disease remains undefined, as patients with CNS involvement have been excluded from pivotal trials. We present the case of a 62-year-old female with high-risk MM who developed extensive leptomeningeal myelomatosis following multiple lines of therapy including autologous transplantation, PI- and IMiD-based regimens, and palliative radiotherapy. Upon presentation with confusion, aphasia, and ataxia, MRI revealed diffuse leptomeningeal enhancement. The patient elected to proceed with teclistamab therapy. Following two cycles, she achieved a very good partial serologic response and MRI demonstrated marked radiologic improvement with resolution of cerebellar nodularity and sulcal enhancement. However, functional recovery was not observed, and the treatment was discontinued after three cycles due to clinical decline and infectious complications. She subsequently transitioned to supportive care and passed away 1 month later. This case report documents one of the first reports of teclistamab demonstrating radiologic improvement in leptomeningeal disease in MM-CNS. While the patient's overall outcome was poor, the observed CNS response supports the biologic plausibility of BiTE penetration and activity in the CNS. These findings suggest the urgent need for prospective studies of BCMA-directed bispecific antibodies in MM-CNS, as well as earlier intervention prior to functional decline.