Posterior reversible encephalopathy syndrome in neuroblastoma patients receiving anti-GD2 3F8 monoclonal antibody

Cancer. 2013 Aug 1;119(15):2789-95. doi: 10.1002/cncr.28137. Epub 2013 Apr 30.

Abstract

Background: Posterior reversible encephalopathy syndrome (PRES) comprises clinical and radiologic findings with rapid onset and potentially dire consequences. Patients experience hypertension, seizures, headache, visual disturbance, and/or altered mentation. Magnetic resonance imaging reveals edematous changes in the brain (especially in the parietal and occipital lobes). In this report, the authors describe PRES associated with antidisialoganglioside (anti-GD2 ) monoclonal antibody (MoAb) immunotherapy, which is now standard for high-risk neuroblastoma but has not previously been implicated in PRES.

Methods: Successive clinical trials using the anti-GD2 MoAb 3F8 (a murine immunoglobulin 3 MoAb specific for GD2) for patients with neuroblastoma involved multiple cycles of standard-dose 3F8 (SD-3F8) (20 mg/m2 daily for 5 days per cycle) or 2 cycles of high-dose 3F8 (HD-3F8) (80 mg/m2 daily for 5 days per cycle) followed by cycles of SD-3F8.

Results: PRES was diagnosed in 5 of 215 patients (2.3%), including 3 of 160 (1.9%) who received SD-3F8 and 2 of 55 (3.6%) who received HD-3F8 (P = .6). All 5 patients had a rapid return to clinical-radiologic baseline. PRES occurred in 3 of 26 patients (11.5%) whose prior treatment included external-beam radiotherapy to the brain (2 of 6 patients status-post total body irradiation and 1 of 20 patients status-post craniospinal irradiation) compared with 2 of 189 patients (1.1%) who had not received prior brain irradiation (P = .01). Hypertension, which is strongly linked to PRES, reached grade 3 toxicity in 12 of 215 patients (5.6%), including the 5 patients with PRES and 7 patients without PRES.

Conclusions: Patients who receive anti-GD2 MoAb immunotherapy should be closely monitored for, and undergo urgent treatment or evaluation of, symptoms that may herald PRES (eg, hypertension or headaches). Prior brain irradiation may be a predisposing factor for PRES with this immunotherapy.

Trial registration: ClinicalTrials.gov NCT00072358 NCT01183416 NCT01183429 NCT01183884 NCT01183897.

Keywords: hypertension; immunotherapy; monoclonal antibodies; neuroblastoma; posterior reversible encephalopathy syndrome.

Publication types

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

MeSH terms

  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Murine-Derived
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy*
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Immunization, Passive / adverse effects
  • Immunization, Passive / methods
  • Immunoglobulin G / adverse effects*
  • Immunoglobulin G / immunology
  • Immunoglobulin G / therapeutic use*
  • Male
  • Neuroblastoma / pathology
  • Neuroblastoma / therapy*
  • Posterior Leukoencephalopathy Syndrome / chemically induced*

Substances

  • 3F8 antibody
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Immunoglobulin G

Associated data

  • ClinicalTrials.gov/NCT00072358
  • ClinicalTrials.gov/NCT01183416
  • ClinicalTrials.gov/NCT01183429
  • ClinicalTrials.gov/NCT01183884
  • ClinicalTrials.gov/NCT01183897