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

TY - JOUR

T1 - 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

AU - Schaefer, Hannah

AU - Rübben, Albert

AU - Esser, André

AU - Araujo, Arturo

AU - Persa, Oana-Diana

AU - Leijs, Marike

A2 - Burger, Michael C.

PY - 2022/8/25

Y1 - 2022/8/25

N2 - 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 =

AB - 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 =

KW - Algorithms

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Fever

KW - Humans

KW - Imidazoles

KW - L-Lactate Dehydrogenase

KW - Melanoma

KW - Mitogen-Activated Protein Kinase Kinases

KW - Mutation

KW - Oximes

KW - Proto-Oncogene Proteins B-raf

KW - Pyridones

KW - Pyrimidinones

KW - Retrospective Studies

KW - Skin Neoplasms

U2 - 10.1371/journal.pone.0273478

DO - 10.1371/journal.pone.0273478

M3 - Article

SN - 1932-6203

VL - 17

SP - e0273478

JO - PLoS One

JF - PLoS One

IS - 8

ER -