Patterns of Central Nervous System Involvement in Relapsed and Refractory Multiple Myeloma

Central nervous system (CNS) involvement in multiple myeloma (MM) usually in advanced relapsed/refractory setting. The current manuscript presents the largest published series of CNS MM cases with malignant cerebrospinal fluid analyses. This report highlights poor prognosis of CNS MM in the era of novel agents and paucity of agents with good CNS penetration. Background: Invasion of CNS in MM is an extremely rare occurrence that is associated with advanced disease with poor prognosis. Patients and Methods: Our MM database identified 35 CNS MM cases presenting between January 1996 and March 2012. Descriptive analyses were performed on available data on patient characteristics, disease course, and outcomes. Results: The mean age at diagnosis was 55.4 years; 23.5% (n = 8) patients had elevated levels of beta-2-microglobulin > 5.5 mg/L; 68.6% (n = 24) of patients had elevated lactate dehydrogenase (LDH) levels (>= 2 times upper limit of normal); and 14% (n = 5) of patients had secondary plasma cell leukemia. Magnetic resonance imaging (MRI), which was performed in 34 patients, showed diffuse or localized leptomeningeal disease in 20 patients (58.8%). Monoclonal malignant plasma cells were found by CSF analysis in all 35 patients. In total, 31 patients received chemotherapy, including intrathecal chemotherapy as a part of their treatment, with a median survival of 4 months after CNS MM diagnosis. Discussion: In our experience, CNS MM is an aggressive terminal disease feature associated with high beta-2-microglobulin level, high LDH level, and secondary plasma cell leukemia. This study highlights an unmet need in this subset of patients with high-risk, relapsed or refractory MM. Conclusion: Achieving adequate CSF penetration while limiting the off-target effects needs to be considered in MM-specific novel drug development. (c) 2014 Elsevier Inc. All rights reserved.