Severe cutaneous and neurologic toxicity in melanoma patients during vemurafenib administration following anti-PD-1 therapy

Cancer Immunol Res. 2013 Dec;1(6):373-7. doi: 10.1158/2326-6066.CIR-13-0092.

Abstract

Immune checkpoint inhibitors such as ipilimumab and targeted BRAF inhibitors have dramatically altered the landscape of melanoma therapeutics over the past few years. Agents targeting the programmed cell death-1/ligand (PD-1/PD-L1) axis are now being developed and appear to be highly active clinically with favorable toxicity profiles. We report two patients with BRAF V600E mutant melanoma who were treated with anti-PD-1 agents as first-line therapy without significant toxicity, followed by vemurafenib at disease progression. Both patients developed severe hypersensitivity drug eruptions with multi-organ injury early in their BRAF inhibitor treatment course. One patient subsequently developed acute inflammatory demyelinating polyneuropathy (AIDP) and the other developed anaphylaxis upon low-dose vemurafenib rechallenge. Further investigation of the immune response during combination or sequences of melanoma therapeutics is warranted. Furthermore, clinicians should maintain a high index of suspicion for these toxicities when vemurafenib is administered following an anti-PD-1 agent.

Keywords: Melanoma; anti-PD-1; immunotherapy; vemurafenib.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aminoquinolines / administration & dosage
  • Aminoquinolines / adverse effects
  • Anaphylaxis / chemically induced
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Drug Eruptions / etiology*
  • Female
  • Guillain-Barre Syndrome / chemically induced*
  • Humans
  • Imiquimod
  • Indoles / administration & dosage
  • Indoles / adverse effects
  • Melanoma / drug therapy*
  • Middle Aged
  • Nivolumab
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Skin Neoplasms / drug therapy*
  • Sulfonamides / administration & dosage
  • Sulfonamides / adverse effects
  • Vemurafenib

Substances

  • Aminoquinolines
  • Antibodies, Monoclonal
  • Indoles
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Sulfonamides
  • Vemurafenib
  • Nivolumab
  • Imiquimod