Natalizumab-Associated Primary Central Nervous System Lymphoma

World Neurosurg. 2018 Jan:109:152-159. doi: 10.1016/j.wneu.2017.09.131. Epub 2017 Sep 28.

Abstract

Objective: Natalizumab, a selective adhesion molecule inhibitor binding to an α-4 subunit of integrin, has emerged to be an effective immunomodulator, especially in the treatment of relapsing-remitting multiple sclerosis and Crohn disease. Recent reports documenting the development of primary central nervous system lymphoma (PCNSL) as a result of its administration have been concerning, and they trigger a debate about a possible causal association. In our report, we provide a comprehensive review of the literature on lymphoma development after natalizumab use, and we report an additional case of PCNSL development in a young woman who received natalizumab for her Crohn disease.

Methods: A systematic (qualitative) review of literature on lymphoma development after natalizumab therapy was performed by use of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data on patient characteristics, indication for drug therapy, dosages, radiologic findings, potential risk factors for PCNSL, and tumor markers were synthesized. Additionally, we present the findings from the case of a young woman who received natalizumab therapy (4 doses, 300 mg each) for Crohn disease and in whom PCNSL developed.

Results: Overall, 8 reports including our index case document lymphoma development after natalizumab use. Our case finding revisits the debate suggesting a remote possibility of association that warrants further evaluation and validation.

Conclusions: Evidence documenting a causal association of natalizumab and PCNSL is weak. Considering the potential benefits of using natalizumab for current indications, we recommend vigilant monitoring of patients receiving the drug for PCNSL outlook.

Keywords: Central nervous system; Craniotomy; Crohn disease; Lymphoma; Multiple sclerosis; Natalizumab; Tsyabri.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Central Nervous System Neoplasms / chemically induced*
  • Humans
  • Immunologic Factors / adverse effects*
  • Lymphoma / chemically induced*
  • Natalizumab / adverse effects*

Substances

  • Immunologic Factors
  • Natalizumab