Abstract

Purpose

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder which commonly causes neoplasms leading to disfigurement or dysfunction. Mitogen-activated protein kinase inhibitors (MEKi) are generally well-tolerated treatments which target neural tumor progression in patients with NF1. However, cutaneous adverse events (CAEs) are common and may hinder patients’ abilities to remain on treatment, particularly in children. We aim to characterize CAEs secondary to MEKi treatment in pediatric and young adult patients with NF1.

Methods

We reviewed institutional medical records of patients under 30 years with a diagnosis of “NF1,” “NF2,” or “other neurofibromatoses” on MEKi therapy between January 1, 2019 and June 1, 2022. We recorded the time-to-onset, type, and distribution of CAEs, non-cutaneous adverse events (AEs), AE management, and tumor response.

Results

Our cohort consisted of 40 patients with NF1 (median age, 14 years). Tumor types included low-grade gliomas (51%) and plexiform neurofibromas (38%). MEKi used included selumetinib (69%), trametinib (25%), and mirdametinib (6%). A total of 74 CAEs occurred, with 28 cases of acneiform rash (38%). Other common CAEs were paronychia, seborrheic dermatitis, eczema, xerosis, and oral mucositis. The most common treatments included oral antibiotics and topical corticosteroids. Most patients had clinical (stable or improved) tumor response (71%) while 29% had tumor progression while on a MEKi. There was no significant association between CAE presence and tumor response (p = 0.39).

Conclusions

Improvement in characterization of MEKi toxicities and their management is important to develop treatment guidelines for pediatric and young adult patients with NF1 on MEKi therapy.

中文翻译：

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丝裂原激活蛋白激酶抑制剂对患有神经纤维瘤病的儿童和年轻人的皮肤毒性-1

摘要

目的

1 型神经纤维瘤病 (NF1) 是一种常染色体显性遗传疾病，通常会导致肿瘤，从而导致毁容或功能障碍。丝裂原激活蛋白激酶抑制剂 (MEKi) 通常是耐受性良好的治疗方法，针对 NF1 患者的神经肿瘤进展。然而，皮肤不良事件 (CAE) 很常见，可能会妨碍患者继续治疗的能力，尤其是儿童。我们的目标是描述 1 型 NF1 儿童和年轻成年患者继发 MEKi 治疗后的 CAE 特征。

方法

我们回顾了 2019 年 1 月 1 日至 2022 年 6 月 1 日期间接受 MEKi 治疗且诊断为“NF1”、“NF2”或“其他神经纤维瘤病”的 30 岁以下患者的机构病历。我们记录了发病时间、 CAE 的类型和分布、非皮肤不良事件 (AE)、AE 管理和肿瘤反应。

结果

我们的队列由 40 名 NF1 患者组成（中位年龄 14 岁）。肿瘤类型包括低级别胶质瘤（51%）和丛状神经纤维瘤（38%）。使用的 MEKi 包括塞美替尼 (selumetinib) (69%)、曲美替尼 (Trametinib) (25%) 和 Mirdametinib (6%)。共发生 74 例 CAE，其中痤疮样皮疹 28 例（38%）。其他常见的 CAE 包括甲沟炎、脂溢性皮炎、湿疹、干燥症和口腔粘膜炎。最常见的治疗包括口服抗生素和外用皮质类固醇。大多数患者在使用 MEKi 期间出现临床（稳定或改善）肿瘤反应（71%），而 29% 的患者出现肿瘤进展。CAE 的存在与肿瘤反应之间没有显着相关性 ( p  = 0.39)。

结论

改善 MEKi 毒性特征及其管理对于制定接受 MEKi 治疗的 NF1 儿童和年轻成人患者的治疗指南非常重要。