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

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 dabr...

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Bibliographic Details
Published in:PloS one 2022-08, Vol.17 (8), p.e0273478
Main Authors: Schaefer, Hannah, Rübben, Albert, Esser, André, Araujo, Arturo, Persa, Oana-Diana, Leijs, Marike
Format: Article
Language:English
Subjects:
Algorithms
Antineoplastic Combined Chemotherapy Protocols - adverse effects
Biology and Life Sciences
Care and treatment
Cluster analysis
Combination therapy
Complications and side effects
Creatinine
Cytokines
Data analysis
Datasets
Dermatology
Drug therapy, Combination
Ethics
Fever
Fever - chemically induced
Hemoglobin
Heuristic methods
Humans
Imidazoles
Inhibitor drugs
Kinases
L-Lactate Dehydrogenase
Laboratories
Lactate dehydrogenase
Lactic acid
Leukocytes
Mathematical analysis
Medicine and Health Sciences
Melanoma
Melanoma - complications
Melanoma - drug therapy
Melanoma - pathology
Melanoma, Cutaneous Malignant
Mitogen-Activated Protein Kinase Kinases
Mutation
Oximes - adverse effects
Patient outcomes
Patients
Physical Sciences
Platelets
Proteins
Proto-Oncogene Proteins B-raf - genetics
Pyridones - adverse effects
Pyrimidinones - adverse effects
Research and Analysis Methods
Retrospective Studies
Skin cancer
Skin Neoplasms - pathology
Statistical analysis
Targeted cancer therapy
Thrombocytes
Values
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Summary: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 =
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0273478