Targets and treatments in primary CNS lymphoma

Leuk Lymphoma. 2024 Aug;65(8):1055-1067. doi: 10.1080/10428194.2024.2342560. Epub 2024 Apr 24.

Abstract

Primary central nervous system lymphoma (PCNSL) is a rare and highly aggressive lymphoma entirely localized in the central nervous system or vitreoretinal space. PCNSL generally initially responds to methotrexate-containing chemotherapy regimens, but progressive or relapsing disease is common, and the prognosis is poor for relapsed or refractory (R/R) patients. PCNSL is often characterized by activation of nuclear factor kappa B (NF-κB) due to mutations in the B-cell receptor (BCR) or toll-like receptor (TLR) pathways, as well as immune evasion. Targeted treatments that inhibit key PCNSL mechanisms and pathways are being evaluated; inhibition of Bruton's tyrosine kinase (BTK) downstream of BCR activation has demonstrated promising results in treating R/R disease. This review will summarize the evidence and potential for targeted therapeutic agents to improve treatment outcomes in PCNSL. This includes immunotherapeutic and immunomodulatory approaches and inhibitors of the key pathways driving PCNSL, such as aberrant BCR and TLR signaling.

Keywords: BCR; BTK; IRAK4; PCNSL; TLR; lymphoma.

Publication types

  • Review

MeSH terms

  • Central Nervous System Neoplasms* / diagnosis
  • Central Nervous System Neoplasms* / drug therapy
  • Central Nervous System Neoplasms* / pathology
  • Central Nervous System Neoplasms* / therapy
  • Disease Management
  • Humans
  • Lymphoma / diagnosis
  • Lymphoma / drug therapy
  • Lymphoma / etiology
  • Lymphoma / genetics
  • Lymphoma / pathology
  • Lymphoma / therapy
  • Molecular Targeted Therapy* / methods
  • Signal Transduction / drug effects