Serum soluble CD163 and proinflammatory chemokines may be biomarkers of the onset of adverse events in dabrafenib plus trametinib combination therapy for advanced melanoma.


Journal

Dermatologic therapy
ISSN: 1529-8019
Titre abrégé: Dermatol Ther
Pays: United States
ID NLM: 9700070

Informations de publication

Date de publication:
01 2021
Historique:
received: 02 09 2020
revised: 31 10 2020
accepted: 11 11 2020
pubmed: 16 11 2020
medline: 25 5 2021
entrez: 15 11 2020
Statut: ppublish

Résumé

Various adverse events (AEs) have been reported to occur at a high rate in patients treated with dabrafenib plus trametinib (D + T) combination therapy. Among such AEs, the incidence of pyrexia was highest among the series of AEs in patients treated with D + T combination therapy. Although little is known about the mechanisms of pyrexia caused by D + T combination therapy, a recent report suggested that sCD163, as well as interferon-inducible chemokines (CXCL9, CXCL10, CXCL11), might correlate with pyrexia caused by encorafenib plus binimetinib combination therapy. In addition to these soluble factors, CXCL5 is a biomarker for predicting immune-related AEs in melanoma patients treated with nivolumab. From the above findings, we hypothesized that these soluble factors might also correlate with the onset of AEs in D + T combination therapy. The serum levels of sCD163 were increased in patients with pyrexia in parallel with their severity, whereas the serum levels of CXCL5 were increased in patients without pyrexia. Moreover, increased levels of CXCL9, CXCL10, and CXCL11 were prominent in patients with AEs over G2 levels. As these chemokines recruit Th1, Th17, and activated CD8+ T cells, increased serum levels of these chemokines might correlate with the positive feedback of inflammatory reactions related to AEs.

Identifiants

pubmed: 33190370
doi: 10.1111/dth.14544
doi:

Substances chimiques

Biomarkers 0
Chemokines 0
Imidazoles 0
Oximes 0
Pyridones 0
Pyrimidinones 0
trametinib 33E86K87QN
Proto-Oncogene Proteins B-raf EC 2.7.11.1
dabrafenib QGP4HA4G1B

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e14544

Subventions

Organisme : Japan Agency for Medical Research and Development
ID : 19cm0106434h0002

Informations de copyright

© 2020 Wiley Periodicals LLC.

Références

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Hu-Lieskovan S, Mok S, Homet Moreno B, et al. Improved antitumor activity of immunotherapy with BRAF and MEK inhibitors in BRAF(V600E) melanoma. Sci Transl Med. 2015;7:279ra41.
Amagai R, Fujimura T, Kambayashi Y, et al. Severe pyrexia from nivolumab-resistant advanced melanoma after successful combined therapy with encorafenib plus binimetinib. J Dermatol. 2020;47:654-657.
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Furudate S, Fujimura T, Kakizaki A, Hidaka T, Asano M, Aiba S. Tumor-associated M2 macrophages in mycosis fungoides aquired immunomodulatory function by interferon alpha and interferon gamma. J Dermatol Sci. 2016;83:182-189.
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Irimada M, Fujimura T, Kambayashi Y, et al. Severe rhabdomyolysis developing from an advanced melanoma patient treated by pembrolizumab followed by dabrafenib trametinib combined therapy. J Dermatol. 2019;46:e256-e258.

Auteurs

Ryo Amagai (R)

Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Taku Fujimura (T)

Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Yusuke Muto (Y)

Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Yumi Kambayashi (Y)

Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Sadanori Furudate (S)

Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Kentaro Ohuchi (K)

Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Takami Okuma (T)

Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Akira Hashimoto (A)

Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Setsuya Aiba (S)

Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.

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