Search

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., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Relapsed/refractory multiple myeloma represents a major challenge in multiple myeloma therapy. For patients with relapsed/refractory multiple myeloma, we developed a treatment schema of metronomically scheduled drug therapy. We identified 186 patients who had been treated with metronomic therapy between March 2004 and January 2012 with a median follow up of 24.2 months. Median age was 61 years (range 36-83). Median number of prior therapies was 14 (range 1-51). Median number of completed metronomic therapy cycles was 1 (range 1-5), while 45 of 186 (25%) received 2 or more cycles. Responses included complete remission in 11 of 186 patients (6%), very good partial remission in 12 of 186 (7%), partial remission in 65 of 179 (36%), and minimal response in 29 of 186 (16%), for an overall response rate of 63% (117 of 186). Median overall survival and progression-free survival were 11.2 and 3.6 months, respectively. Hematologic toxicity grading was problematic as 146 of 186 (78%) of patients presented with at least grade 2 thrombocytopenia within 90 days prior to starting metronomic therapy. Grade 4 leukopenia, anemia, and/or thrombocytopenia following metronomic therapy occurred in 108 of 186 (58%), 12 of 186 (6%), and 147 of 186 (79%) patients, respectively. Incidence of grade 3-4 neutropenic fever was 4 of 186 (2%). Most patients (177 of 186, 95%) were treated in an outpatient unit and secondary admissions due to regimen-related toxicity occurred in 37 of 186 (20%). Treatment-related mortality was evident in 2 of 186 (1%). In conclusion, metronomic therapy is an effective late salvage treatment in relapsed/refractory multiple myeloma, with a high overall response rate and a favorable toxicity profile.