title: Corticosteroids augment BRAF inhibitor vemurafenib induced lymphopenia and risk of infection.
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.
authors.affiliation: Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), Essen, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Sondermann
authors.affiliation: Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), Essen, Germany.
authors.forename: Klaus G
authors.initials: KG
authors.lastname: Griewank
authors.affiliation: Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), Essen, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Schilling
authors.affiliation: Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), Essen, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Livingstone
authors.affiliation: Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), Essen, Germany.
authors.forename: Julia C
authors.initials: JC
authors.lastname: Leyh
authors.affiliation: Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), Essen, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Rompoti
authors.affiliation: Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), Essen, Germany.
authors.forename: Ioana
authors.initials: I
authors.lastname: Cosgarea
authors.affiliation: Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), Essen, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Schimming
authors.affiliation: Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), Essen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
authors.affiliation: Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), Essen, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Zimmer
authors.affiliation: Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), Essen, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Hillen
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000009:adverse effects*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects*; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008231:Lymphopenia / Q000139:chemically induced* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009894:Opportunistic Infections / Q000139:chemically induced* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D010091:Oximes / Q000008:administration & dosage / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies; D012306:Risk; D012878:Skin Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects*; D016019:Survival Analysis; D000077484:Vemurafenib
chemical_list: D000305:Adrenal Cortex Hormones; D007093:Imidazoles; D007211:Indoles; D010091:Oximes; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D000077484:Vemurafenib; D003907:Dexamethasone; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C561627:dabrafenib