Introduction of novel agents in the treatment of primary CNS lymphoma

Neuro Oncol. 2019 Feb 19;21(3):306-313. doi: 10.1093/neuonc/noy193.

Abstract

Novel insights into the pathophysiology of primary central nervous system lymphoma (PCNSL) have identified the B-cell receptor and Toll-like receptor pathway as well as immune evasion and suppressed tumor immune microenvironment as a key mechanism in the pathogenesis of PCNSL. Small molecules and novel agents targeting these aberrant pathways have been introduced into clinical trials targeting the recurrent or refractory PCNSL patient population. Agents like the Bruton tyrosine kinase (BTK) inhibitor ibrutinib or immunomodulatory drugs (IMiDs) like pomalidomide and lenalidomide have shown promising high response rates in the salvage setting. Here, we give an overview about the recent, exciting developments in PCNSL and summarize the results of clinical trials using novel agents in the recurrent and refractory salvage setting, which include immune checkpoint inhibitors, IMiDs, as well as BTK, phosphatidylinositol-3 kinase, and mammalian target of rapamycin inhibitors.

Keywords: BTK; IMiD; PCNSL; immune checkpoint inhibition; targeted agents.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenine / analogs & derivatives
  • Agammaglobulinaemia Tyrosine Kinase / antagonists & inhibitors
  • Aminopyridines / therapeutic use
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Burkitt Lymphoma / drug therapy
  • Central Nervous System Neoplasms / drug therapy*
  • Humans
  • Immunologic Factors / therapeutic use*
  • Lenalidomide / therapeutic use
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Lymphoma, T-Cell / drug therapy
  • Morpholines / therapeutic use
  • Phosphatidylinositol 3-Kinases
  • Phosphoinositide-3 Kinase Inhibitors / therapeutic use
  • Piperidines
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrazoles / therapeutic use
  • Pyrimidines / therapeutic use
  • Rituximab / therapeutic use
  • Salvage Therapy
  • TOR Serine-Threonine Kinases
  • Thalidomide / analogs & derivatives
  • Thalidomide / therapeutic use
  • Toll-Like Receptors
  • Tumor Escape

Substances

  • Aminopyridines
  • Antineoplastic Agents, Immunological
  • Immunologic Factors
  • Morpholines
  • NVP-BKM120
  • Phosphoinositide-3 Kinase Inhibitors
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • Toll-Like Receptors
  • ibrutinib
  • Rituximab
  • Thalidomide
  • pomalidomide
  • Agammaglobulinaemia Tyrosine Kinase
  • TOR Serine-Threonine Kinases
  • Lenalidomide
  • Adenine