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. 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-associated severe skin rash (odds ratio [OR] 1.966, 95% CI, 1.143-3.380, P = .015). CONCLUSIONS: 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.