Immune Checkpoint Inhibitors for the Treatment of Central Nervous System (CNS) Metastatic Disease

Suneel D. Kamath*, Priya U. Kumthekar

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

49 Scopus citations

Abstract

While the CNS has long been viewed as an immune-privileged environment, a paradigm shift in neuro-immunology has elevated the role of systemic immunotherapy for the treatment of metastatic disease. Increasing knowledge regarding the presence of a CNS lymphatic system and the physical and biochemical alteration of the blood brain barrier (BBB) by the tumor microenvironment suggests immune cell trafficking in and out of the CNS is possible. Emerging clinical data suggest immune checkpoint inhibitors (ICIs) can stimulate T cells peripherally to in turn have anti-tumor effects in the CNS. For example, anti-programmed cell death-1 (PD-1) monotherapy with pembrolizumab has shown intracranial response rates of 20–30% in patients with melanoma or non-small cell lung cancer (NSCLC) brain metastases. The combination of nivolumab and ipilimumab [anti-PD-1 and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)] showed an intracranial response rate of 55% in patients with melanoma brain metastases. More data are needed to confirm these response rates and to determine mechanisms of efficacy and resistance. While local therapies such as stereotactic radiosurgery (SRS), whole-brain radiation therapy (WBRT), and surgery remain current mainstays, ICIS offer potential decreased neurotoxicity. This review summarizes the biological rationale for systemic immunotherapy to treat CNS metastatic disease, existing clinical data on ICIs in this setting and ongoing clinical trials exploring areas of unmet need.

Original languageEnglish (US)
Article number414
JournalFrontiers in Oncology
Volume8
DOIs
StatePublished - Sep 27 2018

Keywords

  • CNS metastasis
  • PD-1
  • brain metastasis
  • checkpoint inhibitors
  • immunotherapy
  • ipilimumab
  • nivolumab
  • pembrolizumab

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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