Background: Nearly 5-8% of solid cancers present with leptomeningeal disease (LMD). Patients with LMD have a dismal prognosis with survival measured in weeks-to-months. The pathophysiology of this devastating disease remains unknown.
Methods: A retrospective chart review was performed of twenty-five adult patients with LMD due to melanoma who were enrolled in the MCC 50172 clinical trial between 05/26/2015 and 07/17/2018.
Results: Patients had a median age 63 years (31-80) at diagnosis with LMD. Sixteen had confirmed LMD and five did not meet criteria for LMD, but had positive cerebrospinal fluid (CSF)-circulating tumor cells (CTC’s). Those with LMDhad a median KPS of 70 (30-90) at presentation, and symptoms most commonly included altered mentation n=6 (37%), headaches n=4 (25%), focal weakness n=3 (19%), and paresthesia n=2 (12%). Eleven patients were diagnosed by MRI. Ten patients (62%) had positive CSF cytology on first attempt and fourteen (87%) on first-two attempts. Lumbar puncture mean OP was 29.4 cmH2O (18-65), with CSF WBC 21.8/cumm (SD 25.6), RBC 2942.5/cumm (SD 9056.1), and protein 187.6 mg/dL (SD 166.1). CSF-CTC’sCellSearchanalysishad a sensitivity of 0.75 (12[12+4]) and specificity of 0.44 (4[4+5]); PPV 0.71 and NPV 0.50. Twelve patients with LMD had positive CSF-CTC’s. Prior to LMD diagnosis, patients were treated with immune checkpoint inhibitors (ICI’s) n=9 (56%), BRAF+/-MEK inhibitors n=5 (31%), and/or RT n=5 (31%). Patients with LMDwere treatedwith Ommaya n=13 +VPS n=3 , WBRT n=7, ICI’s n=5, BRAF+MEK inhibitors n=4, and IT topotecan. LMD patients had a median survival 3.27 months after diagnosis (0.30-39). Two patients outlived their counterparts by 21.1 and 39.0 months. The 2 long-term survivors were treated with WBRT and either ICI, pembrolizumab or ipilimumab+nivolumab.
Conclusion: Clinical studies in LMD can provide critical insights and help to develop improved guidelines and current therapies.