Abstract
Various serious adverse events (AE) have been reported to occur at a high rate in patients treated with BRAF plus mitogen-activated protein kinase kinase (MEK) inhibitor combination therapy, but their subtypes differ among the BRAF/MEK inhibitors. Pyrexia or a spike of fever are well-known AE of BRAF inhibitors, with or without MEK inhibitors, and have been reported to have a high incidence after dabrafenib/trametinib, but not after encorafenib/binimetinib. In this report, we describe three cases of severe pyrexia in nivolumab-resistant advanced melanoma after successful combined therapy with encorafenib plus binimetinib. Interestingly, in all cases, the serum levels of soluble CD163 C-X-C motif chemokine (CXCL)9, CXCL10 and CXCL11, which are known biomarkers for adult-onset Still's disease (AOSD), increased in parallel with the development of pyrexia. Our present cases suggest that pyrexia caused by BRAF/MEK inhibitors may possess a similar pathophysiology as that of AOSD.
Keywords:
adult-onset Still’s disease; adverse events; encorafenib plus binimetinib combined therapy; nivolumab; pyrexia.
© 2020 Japanese Dermatological Association.
MeSH terms
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Adult
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Aged
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Antineoplastic Combined Chemotherapy Protocols / administration & dosage
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Antineoplastic Combined Chemotherapy Protocols / adverse effects*
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Benzimidazoles / administration & dosage
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Benzimidazoles / adverse effects
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Carbamates / administration & dosage
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Carbamates / adverse effects
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Drug Resistance, Neoplasm
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Female
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Fever / chemically induced*
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Humans
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Lymph Nodes / diagnostic imaging
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Lymphatic Metastasis / diagnosis
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Lymphatic Metastasis / therapy*
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Male
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Melanoma / diagnosis
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Melanoma / drug therapy*
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Melanoma / secondary
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Middle Aged
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Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
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Nivolumab / pharmacology
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Nivolumab / therapeutic use
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Positron Emission Tomography Computed Tomography
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Protein Kinase Inhibitors / administration & dosage
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Protein Kinase Inhibitors / adverse effects*
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Proto-Oncogene Proteins B-raf / antagonists & inhibitors
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Skin Neoplasms / diagnosis
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Skin Neoplasms / drug therapy*
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Skin Neoplasms / pathology
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Sulfonamides / administration & dosage
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Sulfonamides / adverse effects
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Treatment Outcome
Substances
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Benzimidazoles
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Carbamates
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Protein Kinase Inhibitors
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Sulfonamides
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binimetinib
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Nivolumab
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encorafenib
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BRAF protein, human
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Proto-Oncogene Proteins B-raf
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Mitogen-Activated Protein Kinase Kinases