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

作者：Xiaoman Liu, Mengying Pi, Mukai Chen, Shirong Cai, Yulong He, Kejing Tang, Xinhua Zhang, Yanzhe Xia · 发表于：The Oncologist · 年份：2025 · DOI：10.1093/oncolo/oyaf176 · 被引用次数：1 · 研究领域：Gastrointestinal Tumor Research and Treatment、Gastrointestinal disorders and treatments、Urticaria and Related Conditions

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. 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 = .004) and was associated with lower final maintenance doses of imatinib after desensitization (P = .010). The final imatinib trough concentrations postdesensitization were significantly lower than those at rash onset (P < .001). Pharmacogenetic analysis identified IL-6R rs4129267 as significantly associated with imatinib-associat...