Abstract
Central nervous system (CNS) involvement in multiple myeloma (MM) is a rare but serious complication that poses significant diagnostic and therapeutic challenges. This article presents three cases of leptomeningeal involvement in patients with MM, highlighting the diverse clinical presentations, diagnostic approaches, and treatment strategies employed. The first case is a 54-year-old female who, after initial treatment and autologous hematopoietic stem cell transplant, developed CNS disease. Similarly, a 73-year-old female developed leptomeningeal involvement with progressive neurological symptoms. The third case describes a 63-year-old female with immunoglobulin (Ig)A lambda MM who developed CNS disease after treatment with daratumumab and radiation. In all three cases, leptomeningeal enhancement and atypical plasma cells were identified in cerebrospinal fluid (CSF), with treatment strategies including intrathecal chemotherapy, systemic therapy, radiation, and stem cell transplantation. Despite aggressive management, including novel agents and supportive care, all patients had poor outcomes, with two transitioning to hospice care. The article reviews the limited literature on CNS-MM, noting the lack of standardized treatment protocols and the need for further research. As the survival of MM patients improves, the incidence of CNS involvement is expected to rise, making the development of targeted therapies essential. These cases underscore the urgent need for further investigation into novel treatment options and the importance of early diagnosis and comprehensive management of CNS-MM.