Abstract
We have previously demonstrated an impact of the BRAF inhibitor vemurafenib on patient lymphocyte counts. In the current study, the extent to which concomitant use of corticosteroids in BRAF inhibitor treated patients affects lymphocyte counts and predisposes to infection was investigated. A cohort of 102 patients receiving either the selective BRAF inhibitor vemurafenib or dabrafenib was analyzed. The amount of patients receiving either medication with or without systemic corticosteroids (dexamethasone) was determined and lymphocyte counts before and under therapy assessed. Additionally, the number and severity of infections occurring in these groups was analyzed. Vemurafenib treatment led to a considerable decrease in lymphocyte cell counts, with 62.3% of patients having lymphopenia. Dabrafenib treated patients only rarely demonstrated lymphopenia (12.5%). Dexamethasone co-administration further diminished lymphocyte counts. Lymphopenias were observed in 84.6% of patients receiving vemurafenib and dexamethasone. In our cohort, infections were noted in 9 patients, 4 of these were severe and 2 eventually fatal. All 9 cases with infections demonstrated lymphopenia, 8 of these had received dexamethasone and 7 of these a therapy with vemurafenib. Our findings demonstrate a significant lymphopenia in patients treated with the BRAF inhibitor vemurafenib, which is further augmented by dexamethasone and predisposes to infection. If validated in other studies, risk of infection should be considered when applying corticosteroids in combination with BRAF inhibitors, in particular vemurafenib.
MeSH terms
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Adrenal Cortex Hormones / administration & dosage
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Adrenal Cortex Hormones / adverse effects*
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Adult
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Aged
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Aged, 80 and over
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Antineoplastic Combined Chemotherapy Protocols / administration & dosage
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Antineoplastic Combined Chemotherapy Protocols / adverse effects*
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Dexamethasone / administration & dosage
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Dexamethasone / adverse effects*
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Female
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Gene Expression
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Humans
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Imidazoles / administration & dosage
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Imidazoles / therapeutic use
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Indoles / administration & dosage
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Indoles / adverse effects*
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Lymphocyte Count
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Lymphocytes / drug effects
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Lymphocytes / metabolism
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Lymphocytes / pathology
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Lymphopenia / chemically induced*
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Lymphopenia / genetics
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Lymphopenia / mortality
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Lymphopenia / pathology
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Male
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Melanoma / drug therapy
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Melanoma / genetics
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Melanoma / mortality
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Melanoma / pathology
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Middle Aged
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Opportunistic Infections / chemically induced*
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Opportunistic Infections / genetics
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Opportunistic Infections / mortality
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Opportunistic Infections / pathology
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Oximes / administration & dosage
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Oximes / therapeutic use
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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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Proto-Oncogene Proteins B-raf / genetics
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Proto-Oncogene Proteins B-raf / metabolism
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Retrospective Studies
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Risk
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Skin Neoplasms / drug therapy
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Skin Neoplasms / genetics
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Skin Neoplasms / mortality
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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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Survival Analysis
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Vemurafenib
Substances
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Adrenal Cortex Hormones
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Imidazoles
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Indoles
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Oximes
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Protein Kinase Inhibitors
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Sulfonamides
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Vemurafenib
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Dexamethasone
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BRAF protein, human
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Proto-Oncogene Proteins B-raf
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dabrafenib
Grants and funding
The authors have no support or funding to report.