Hemophagocytic lymphohistiocytosis induced by dabrafenib-trametinib in a patient with metastatic melanoma: a case report and pharmacovigilance analysis

Melanoma Res. 2024 Oct 1;34(5):465-468. doi: 10.1097/CMR.0000000000000992. Epub 2024 Jul 22.

Abstract

Hemophagocytic lymphohistiocytosis (HLH) has been reported rarely with BRAF/MEK inhibitor combinations, including dabrafenib/trametinib. Postmarketing pharmacovigilance analyses evaluating outcomes associated with dabrafenib/trametinib-induced HLH are also lacking. Herein, we report a case of dabrafenib/trametinib-induced HLH in a patient with metastatic melanoma. Recovery of HLH-related symptoms was observed following drug discontinuation, supportive care, and corticosteroids. We also conducted a pharmacovigilance analysis of the USA Food and Drug Administration Adverse Event Reporting System (FAERS) to describe postmarketing cases of HLH with dabrafenib/trametinib exposure. There were 50 reports of HLH with dabrafenib/trametinib in FAERS. Most cases occurred in the setting of melanoma ( n = 39; 78%) and most were reported in Europe ( n = 39; 74%). Hospitalization was the most common outcome ( n = 39; 78%) of this adverse event per FAERS. HLH is a rare complication of dabrafenib/trametinib, and clinicians should be aware and monitor for signs of this potentially serious and life-threatening adverse event.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Female
  • Humans
  • Imidazoles* / administration & dosage
  • Imidazoles* / adverse effects
  • Lymphohistiocytosis, Hemophagocytic* / chemically induced
  • Male
  • Melanoma* / drug therapy
  • Middle Aged
  • Oximes* / administration & dosage
  • Oximes* / adverse effects
  • Oximes* / therapeutic use
  • Pharmacovigilance
  • Pyridones* / adverse effects
  • Pyrimidinones* / administration & dosage
  • Pyrimidinones* / adverse effects
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / pathology

Substances

  • dabrafenib
  • Imidazoles
  • Oximes
  • Pyrimidinones
  • trametinib
  • Pyridones