The management of imatinib-associated severe skin rash in gastrointestinal stromal tumor: desensitization therapy and pharmacogenetic investigation.

IF 4.8 2区医学 Q1 ONCOLOGY

Oncologist Pub Date : 2025-07-02 DOI:10.1093/oncolo/oyaf176

Xiaoman Liu, Mengying Pi, Mukai Chen, Shirong Cai, Yulong He, Ke-Jing Tang, Xinhua Zhang, Yanzhe Xia

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引用次数: 0

Abstract

Background: Skin rash is one of the most common imatinib-associated adverse events in patients with gastrointestinal stromal tumors (GISTs), potentially compromising treatment adherence and therapeutic efficacy. This study presents a personalized desensitization management of imatinib-associated severe rash with therapeutic drug monitoring (TDM) and pharmacogenetic investigation.

Patients and methods: Among 712 patients with GIST receiving imatinib, 54 patients (7.6%) developed severe skin rash (grade 3: 37 patients, recurrent grade 2: 17 patients) and underwent personalized desensitization treatment. This approach involved a temporary cessation of imatinib and initiation of systemic steroids, followed by reintroduction of imatinib with TDM-assisted gradual dose escalation, while steroids were tapered until discontinuation. Pharmacogenetic analysis was conducted to explore potential genetic susceptibility.

Results: Following desensitization therapy for severe rash, the majority of patients (92.6%) successfully resumed imatinib treatment at personalized maintenance doses. Grade 3 rash occurred earlier than recurrent grade 2 rash before desensitization therapy (P = 0.004) and was associated with lower final maintenance doses of imatinib after desensitization (P = 0.010). The final imatinib trough concentrations post-desensitization were significantly lower than those at rash onset (P < 0.001). Pharmacogenetic analysis identified IL-6R rs4129267 as significantly associated with imatinib-associated severe skin rash (odds ratio 1.966, 95% CI, 1.143-3.380, P = 0.015).

Conclusion: Personalized desensitization therapy assisted by TDM could effectively manage imatinib-associated severe skin rash. The early onset of grade 3 rash underscored the importance of vigilant monitoring during the initial phase of imatinib treatment. Genetic variant in IL-6R may be involved in rash pathogenesis.

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胃肠道间质瘤中伊马替尼相关严重皮疹的处理：脱敏治疗和药理学研究。

背景：皮疹是胃肠道间质瘤（gist）患者中最常见的伊马替尼相关不良事件之一，可能影响治疗依从性和治疗效果。本研究提出了一种个性化的伊马替尼相关严重皮疹脱敏管理与治疗药物监测（TDM）和药理学研究。患者和方法：在接受伊马替尼治疗的712例GIST患者中，54例（7.6%）患者出现严重皮疹（3级37例，复发2级17例），并接受个性化脱敏治疗。该方法包括暂时停用伊马替尼并开始全体性类固醇，随后在tdm辅助下逐渐增加剂量的情况下重新引入伊马替尼，同时逐渐减少类固醇直至停用。进行药物遗传学分析，探讨潜在的遗传易感性。结果：重度皮疹脱敏治疗后，大多数患者（92.6%）成功恢复伊马替尼个体化维持剂量治疗。3级皮疹比脱敏治疗前复发的2级皮疹发生得早（P = 0.004），并且与脱敏治疗后伊马替尼的最终维持剂量较低相关（P = 0.010）。脱敏后最终伊马替尼谷浓度显著低于起疹时（P < 0.001）。药理学分析发现IL-6R rs4129267与伊马替尼相关的严重皮疹显著相关（优势比1.966,95% CI, 1.143-3.380, P = 0.015）。结论：TDM辅助个体化脱敏治疗可有效治疗伊马替尼相关性严重皮疹。3级皮疹的早期发作强调了在伊马替尼治疗初始阶段警惕监测的重要性。IL-6R基因变异可能与皮疹发病有关。

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来源期刊

Oncologist 医学-肿瘤学

CiteScore

10.40

自引率

3.40%

发文量

309

审稿时长

3-8 weeks

期刊介绍： The Oncologist® is dedicated to translating the latest research developments into the best multidimensional care for cancer patients. Thus, The Oncologist is committed to helping physicians excel in this ever-expanding environment through the publication of timely reviews, original studies, and commentaries on important developments. We believe that the practice of oncology requires both an understanding of a range of disciplines encompassing basic science related to cancer, translational research, and clinical practice, but also the socioeconomic and psychosocial factors that determine access to care and quality of life and function following cancer treatment.