Schaefer, Hannah, Ruebben, Albert, Esser, Andre, Araujo, Arturo ORCID: 0000-0002-0269-2819, Persa, Oana-Diana and Leijs, Marike (2022). 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. PLoS One, 17 (8). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

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 thrombo-cytes, 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 = <0.0001) and showed a significant predictive value for the diagnosis of pyrexia (F = 6.24; p = 0.013). We provide first evidence that pyrexia in patients treated with BRAF/MEK-blockade can be identified by an algorithm that calculates a score.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Schaefer, HannahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ruebben, AlbertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Esser, AndreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Araujo, ArturoUNSPECIFIEDorcid.org/0000-0002-0269-2819UNSPECIFIED
Persa, Oana-DianaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leijs, MarikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-684255
DOI: 10.1371/journal.pone.0273478
Journal or Publication Title: PLoS One
Volume: 17
Number: 8
Date: 2022
Publisher: PUBLIC LIBRARY SCIENCE
Place of Publication: SAN FRANCISCO
ISSN: 1932-6203
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PLUS TRAMETINIB; MEK INHIBITION; COMBINED BRAF; MANAGEMENT; TOXICITIES; SURVIVALMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/68425

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