Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
J Dermatol. 2020 Jun;47(6):654-657. doi: 10.1111/1346-8138.15346. Epub 2020 Apr 15.
Various serious adverse events (AE) have been reported to occur at a high rate in patients treated with BRAF plus mitogen-activated protein kinase kinase (MEK) inhibitor combination therapy, but their subtypes differ among the BRAF/MEK inhibitors. Pyrexia or a spike of fever are well-known AE of BRAF inhibitors, with or without MEK inhibitors, and have been reported to have a high incidence after dabrafenib/trametinib, but not after encorafenib/binimetinib. In this report, we describe three cases of severe pyrexia in nivolumab-resistant advanced melanoma after successful combined therapy with encorafenib plus binimetinib. Interestingly, in all cases, the serum levels of soluble CD163 C-X-C motif chemokine (CXCL)9, CXCL10 and CXCL11, which are known biomarkers for adult-onset Still's disease (AOSD), increased in parallel with the development of pyrexia. Our present cases suggest that pyrexia caused by BRAF/MEK inhibitors may possess a similar pathophysiology as that of AOSD.
各种严重的不良反应（AE）已被报道在接受 BRAF 加丝裂原活化蛋白激酶激酶（MEK）抑制剂联合治疗的患者中以高频率发生，但它们的亚型在 BRAF/MEK 抑制剂之间有所不同。发热或高热是 BRAF 抑制剂的众所周知的 AE，无论是否有 MEK 抑制剂，在 dabrafenib/trametinib 后已被报道有高发生率，但 encorafenib/binimetinib 后则没有。在本报告中，我们描述了三例在 nivolumab 耐药性晚期黑色素瘤患者中成功接受 encorafenib 加 binimetinib 联合治疗后出现严重发热的病例。有趣的是，在所有病例中，已知作为成人Still 病（AOSD）的生物标志物的可溶性 CD163 C-X-C 基序趋化因子（CXCL）9、CXCL10 和 CXCL11 的血清水平与发热的发展平行增加。我们目前的病例表明，BRAF/MEK 抑制剂引起的发热可能具有与 AOSD 相似的病理生理学。
