The Role of Immune Checkpoint Inhibitors in Leptomeningeal Disease: A Systematic Review
Paolo Palmisciano, Ali S. Haider, Chibueze D. Nwagwu, Waseem Wahood, Kenny Yu, Chibawanye Ene, Barbara O’Brien, Salah G. Aoun, Aaron Cohen‐Gadol, Tarek Y. El Ahmadieh
Abstract
BACKGROUND/AIM: Leptomeningeal disease (LMD) is a debilitating complication of advanced malignancies. Immune-checkpoint inhibitors (ICIs) may alter disease course. We analyzed the role and toxicity of ICIs in LMD. MATERIALS AND METHODS: We systematically reviewed the literature reporting on outcome data of patients with LMD treated with ICIs. RESULTS: We included 14 studies encompassing 61 patients. Lung-cancer (44.3%), breast-cancer (27.9%), and melanoma (23.0%) were the most frequent primary tumors. Median duration of ICI-treatment was 7-months (range=0.5-58.0): pembrolizumab (49.2%), nivolumab (32.8%), ipilimumab (18.0%). Radiological responses included complete response (33.3%), partial response (12.5%), stable disease (33.3%), progressive disease (20.8%). Twenty-two patients developed ICI-related adverse-events, mild (100%) and/or severe (15.6%). Median progression-free and overall survival were 5.1 and 6.3 months, and 12-month survival was 32.1%. Survival correlated with ICI agents (p=0.042), but not with primary tumors (p=0.144). Patients receiving concurrent steroids showed worse survival (p=0.040). CONCLUSION: ICI therapy is well-tolerated in patients with LMD, but concurrent steroids may worsen survival.