Nurse Practitioner MD Anderson Cancer Center Houston, Texas, United States
Introduction: Despite advances in multiple myeloma (MM) treatment, systemic therapy alone for central nervous system (CNS) MM is often ineffective. While intrathecal (IT) chemo with cytarabine, methotrexate or topotecan, and/or radiation may result in transient responses, the median overall survival (OS) for patients with CNS involvement ranges between 2-10 months.
Methods: This single center retrospective review of patients (pts) with CNS MM (diagnosed as CSF plasma cells, parenchymal and/or leptomeningeal disease (LMD) on imaging) from 2016-2023 were identified in the medical records. We aim to identify factors associated with development of CNS MM, overall survival from initial MM diagnosis (dx) and from onset of CNS, and progression free survival (PFS). Further analyses will include patients with radiographic findings of CNS involvement and patients with extramedullary disease (EMD). Pts with EMD will be analyzed to identify factors associated with EMD, OS, and development of CNS disease.
Results: 35 pts were identified who had clonal plasma cells in the CSF: 15 (42.8%) were White, 12 (34.2%) were Hispanic, 6 (17.1%) were Black, and 2 (5.7%) were Asian. 54.2% were males, and 62.8% were kappa predominant. Median age at diagnosis was 57 (range 25-77). Among 27 pts with R-ISS available, 4 (14%) had stage I disease, 14 (51%) had Stage II, and 9 (33%) had stage III. Of 20 evaluable patients with FISH panels, we noted deletion 13 (70%), gain of CKS1B (70%), t(4;14) (35%), deletion of 17p (15%), and t(11;14) (10%). Of the 14 pts with gain of CKS1B, 11 also had deletion 13. Most common symptoms included weakness of the extremities and/or difficulty ambulating (32%), facial or extremity numbness (26%), altered mental status (26%), headaches (17.6%), diplopia (14.7%), and seizure (8.8%). 21 pts (60%) presented with EMD prior to presenting with CNS disease (median time to CNS involvement after EMD was 35-months [range 1-35]). The most common sites for EMD included pleura/lung (8 patients), adenopathy (7 patients), pancreas (6 patients), GI tract (4 patients), subcutaneous tissues (3 patients), and intramuscular (2 patients) with all but one having multiple sites of disease. The median PFS to first line therapy was 18 months (range 1-97 months) and the median time from MM diagnosis to CNS disease was 38 months (range 1-99 months). The median OS was 41 months (range 5-120months). Median OS after CNS diagnosis was 3 months (range 1-51 months).
Conclusions: In our analysis, pts with CNS MM had a poor prognosis with a median OS of 3 months from the time of CNS diagnosis, highlighting the need for more effective therapy. In this group of patients, the PFS to first line therapy was short, despite only 9 patients having high risk disease, solidifying that EMD should be treated as a high risk feature independent of other factors. Additionally, 60% presented with EMD prior to CNS involvement. Further analysis of pts with EMD is warranted, which may include CNS prophylaxis in certain patients with EMD.
