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Robotic Duodenal Sleeve Resection for Gastrointestinal Stromal Tumor with Rare Exon 8 KIT Mutation Following Neoadjuvant Imatinib
Published on: April 3, 2026
Phase II study of imatinib mesylate as therapy for patients with systemic mastocytosis
Arturo Vega-Ruiz1, Jorge E Cortes, Matjaz Sever
1Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
Abstract:
Gain-of-function D816V point mutation within the kinase domain of the transmembrane receptor KIT is found in the great majority of patients with systemic mastocytosis (SM) and is attractive therapeutic target. Twenty patients with SM were enrolled during 2003-2005 in phase II clinical trial with imatinib mesylate (400mg daily), a KIT inhibitor. Median time on therapy was 9 months (range, 0.5-44+). Only one patient, with D816V KIT mutation-negative FIP1L1-PDGFRalpha-negative SM-HES, achieved complete remission (now lasting for 44 months). Six other patients reported symptomatic improvement, including two with D816V KIT mutation-positive SM (one reported improvement in diarrhea and the other in fatigue). Other patients had no benefit. Imatinib was relatively well tolerated. Our study confirms that imatinib therapy does not result in appreciable clinical activity in patients with D816V mutation-positive SM, but may result in a significant benefit in occasional patient with D816V mutation-negative SM.
Insights
Imatinib therapy showed limited efficacy in systemic mastocytosis (SM) patients with the KIT D816V mutation. However, some patients without this mutation experienced symptomatic improvement, indicating potential benefit in specific SM subtypes.
Area of Science:
- Hematology
- Oncology
- Pharmacology
Background:
- Systemic mastocytosis (SM) is often driven by the KIT D816V mutation.
- This mutation makes the KIT receptor a key therapeutic target.
Purpose of the Study:
- To evaluate the efficacy and tolerability of imatinib mesylate in patients with systemic mastocytosis.
- To assess the impact of the KIT D816V mutation status on treatment response.
Main Methods:
- A Phase II clinical trial involving 20 SM patients treated with imatinib mesylate (400mg daily).
- Patients were monitored for clinical response, symptomatic improvement, and adverse events.
- KIT D816V mutation status was assessed for correlation with outcomes.
Main Results:
- Only one patient, negative for KIT D816V and FIP1L1-PDGFRalpha mutations, achieved complete remission.
- Two patients with KIT D816V-positive SM reported symptomatic improvement (diarrhea, fatigue).
- Imatinib was generally well-tolerated, but overall clinical activity in D816V-positive SM was limited.
Conclusions:
- Imatinib mesylate demonstrates minimal clinical activity in systemic mastocytosis patients with the common KIT D816V mutation.
- Occasional patients with D816V-negative SM may experience significant clinical benefit from imatinib therapy.
- Further research into targeted therapies for D816V-mutated SM is warranted.
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