The Role of Immune Checkpoint Inhibitors in Leptomeningeal Disease: A Systematic Review

Anticancer Res. 2021 Nov;41(11):5333-5342. doi: 10.21873/anticanres.15346.

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.

Keywords: Brain metastasis; corticosteroids; immune checkpoint inhibitors; immunotherapy; leptomeningeal disease; review.

Publication types

  • Systematic Review

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Disease Progression
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / adverse effects
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Male
  • Meningeal Neoplasms / drug therapy*
  • Meningeal Neoplasms / immunology
  • Meningeal Neoplasms / mortality
  • Meningeal Neoplasms / secondary
  • Middle Aged
  • Progression-Free Survival
  • Risk Assessment
  • Risk Factors
  • Steroids / adverse effects
  • Time Factors
  • Tumor Microenvironment

Substances

  • Immune Checkpoint Inhibitors
  • Steroids