Nivolumab-ipilimumab combination therapy-induced seronegative encephalitis; rapid response to steroid plus intravenous immunoglobulin (IVIG) treatment

J Oncol Pharm Pract. 2023 Apr;29(3):760-763. doi: 10.1177/10781552221118529. Epub 2022 Aug 8.

Abstract

Introduction: The efficacy of immune checkpoint inhibitors (ICIs) against malignant melanoma and numerously solid tumors has been demonstrated in several clinical studies. The incidence of immune-related adverse effects (irAEs) has increased after the rapidly expanding indications and clinical applications of ICIs. We present a case of nivolumab and ipilimumab-induced encephalitis with rapidly worsening consciousness and full recovery following ICIs suspension and high-dose steroid coupled with intravenous immunoglobulin (IVIG).

Case report: A 67-year-old woman was diagnosed with stage 4 BRAF wild malignant melanoma with metastasis to the axillary and mediastinal lymph nodes. Beyond progression with dacarbazine, ipilimumab and nivolumab combination were administered at the second-line treatment of metastatic setting. A week after the first cycle patient was reported to have a fever of more than 38°C. Subacute cognitive impairment including mild changes in behavior was reported on the third day of fever. She suddenly developed confusion, dysarthria, and motor dysfunction a few days later. Due to the altered mental status accompanied by fever, lumbar puncture was performed with a pre-diagnosis of encephalitis, meningitis, and leptomeningeal carcinomatosis.

Management & outcome: After excluding viral and autoimmune encephalitis, high-dose methylprednisolone was administered in addition to IVIG for 5 days with the diagnosis of immunotherapy-related encephalitis according to the recommendations for the management of irAEs. On the second day of the treatment patient's neurological status improved gradually.

Discussion: Being aware of symptoms of serious neurological irAEs associated with ICIs can prevent complications and improve survival.

Keywords: Encephalitis; immune checkpoint inhibitors; immune-related adverse effects; malignant melanoma.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Drug-Related Side Effects and Adverse Reactions* / drug therapy
  • Encephalitis* / chemically induced
  • Encephalitis* / drug therapy
  • Female
  • Humans
  • Immunoglobulins, Intravenous / therapeutic use
  • Ipilimumab / adverse effects
  • Melanoma* / pathology
  • Melanoma, Cutaneous Malignant
  • Nivolumab / adverse effects
  • Steroids / therapeutic use

Substances

  • Nivolumab
  • Ipilimumab
  • Immunoglobulins, Intravenous
  • Steroids