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.
Highlights
Melanoma is a malignant cutaneous neoplasm and responsible for a considerable mortality worldwide[1]
The aim of our study was to retrospectively analyze to which extent patients treated with the BRAF V600 inhibitors (BRAFi) VEM or DAB received corticosteroids, how this treatment affected lymphocyte counts and whether this had a relevant impact on clinical parameters such as infections
We recognize a considerable amount of patients who experienced severe lymphopenias while under BRAFi treatment
Summary
Melanoma is a malignant cutaneous neoplasm and responsible for a considerable mortality worldwide[1]. In the United States, 9710 people were expected to die of melanoma in 2014[2]. Merck Sharp & Dohme, and Merck, and travel support from Bristol-Myers Squibb. Lisa Zimmer has received honoraria from Roche, BristolMyers Squibb, Boehringer Ingelheim and Amgen, and travel support from Merck Sharp & Dohme and Bristol-Myers Squibb. Dirk Schadendorf is on the advisory board or has received honoraria from Roche, Genentech, Novartis, Amgen, GlaxoSmithKline, Bristol-Myers Squibb, Boehringer Ingelheim, and Merck Sharp & Dohme. The remaining authors have declared no conflicts of interest. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials
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