A distinct four-value blood signature of pyrexia under combination therapy of malignant melanoma with dabrafenib and trametinib evidenced by an algorithm-defined pyrexia score

Hannah Schaefer, Albert Rübben, André Esser, Arturo Araujo, Oana-Diana Persa, Marike Leijs, Michael C. Burger (Editor)

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    Pyrexia is a frequent adverse event of BRAF/MEK-inhibitor combination therapy in patients with metastasized malignant melanoma (MM). The study’s objective was to identify laboratory changes which might correlate with the appearance of pyrexia. Initially, data of 38 MM patients treated with dabrafenib plus trametinib, of which 14 patients developed pyrexia, were analysed retrospectively. Graphical visualization of time series of laboratory values suggested that a rise in C-reactive-protein, in parallel with a fall of leukocytes and thrombocytes, were indicative of pyrexia. Additionally, statistical analysis showed a significant correlation between lactate dehydrogenase (LDH) and pyrexia. An algorithm based on these observations was designed using a deductive and heuristic approach in order to calculate a pyrexia score (PS) for each laboratory assessment in treated patients. A second independent data set of 28 MM patients, 8 with pyrexia, was used for the validation of the algorithm. PS based on the four parameters CRP, LDH, leukocyte and thrombocyte numbers, were statistically significantly higher in pyrexia patients, differentiated between groups (F = 20.8; p =
    Original languageEnglish
    Pages (from-to)e0273478
    JournalPLoS One
    Issue number8
    Early online date25 Aug 2022
    Publication statusE-pub ahead of print - 25 Aug 2022


    • Algorithms
    • Antineoplastic Combined Chemotherapy Protocols
    • Fever
    • Humans
    • Imidazoles
    • L-Lactate Dehydrogenase
    • Melanoma
    • Mitogen-Activated Protein Kinase Kinases
    • Mutation
    • Oximes
    • Proto-Oncogene Proteins B-raf
    • Pyridones
    • Pyrimidinones
    • Retrospective Studies
    • Skin Neoplasms

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