Avapritinib treatment of aggressive systemic mastocytosis with a novel KIT exon 17 mutation

IF 0.7 Q4 HEMATOLOGY Leukemia Research Reports Pub Date : 2024-01-01 DOI:10.1016/j.lrr.2023.100409
Lyndsey Sandow , Ajia Town , Michael C. Heinrich
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Abstract

Background

Systemic mastocytosis is a rare hematologic malignancy that leads to the accumulation of neoplastic mast cells in the bone marrow, visceral organs, and skin. Mutations in the receptor tyrosine kinase, KIT are seen in most patients with systemic mastocytosis. The most common mutation is a gain of function mutation in KIT D816V. Avapritinib is a highly selective KIT D816V inhibitor approved for the treatment of advanced systemic mastocytosis. Recent studies have also suggested that avapritinib is active across other KIT mutations located in exon 11 and exon 17.

Case Presentation

A 68 year old woman was referred for a history of lymphadenopathy and diarrhea and was ultimately found to have systemic mastocytosis with involvement in her bone marrow, gastrointestinal tract, liver, and spleen. The bone marrow biopsy reveled a novel KIT p.D816-N822delinsMIDSI mutation in exon 17. The patient was started on avapritinib leading to significant decrease in the frequency of her diarrhea and a significant reduction in her tryptase levels. Her course was complicated by arthralgias leading to a decrease in her avapritinib dose and ultimately a degranulation episode requiring hospitalization. Following dose re-escalation, patient has remained clinically stable without any further adverse events.

Conclusion

We report a case of aggressive systemic mastocytosis with a novel KIT mutation on exon 17 treated with avapritinib leading to a sustained response. While avapritinib is known as a potent inhibitor against the D816V mutation, our case suggests that it may also be effective against other rare KIT mutations in systemic mastocytosis offering more potential treatment options in patients with rare mutations.

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阿伐替尼治疗伴有新型 KIT 第 17 号外显子突变的侵袭性系统性肥大细胞增多症
背景系统性肥大细胞增多症是一种罕见的血液系统恶性肿瘤,会导致肿瘤性肥大细胞在骨髓、内脏器官和皮肤中聚集。大多数系统性肥大细胞增多症患者的受体酪氨酸激酶 KIT 发生突变。最常见的突变是 KIT D816V 功能增益突变。阿伐普替尼是一种高选择性 KIT D816V 抑制剂,已被批准用于治疗晚期系统性肥大细胞增多症。最近的研究还表明,阿伐替尼对位于外显子 11 和外显子 17 的其他 KIT 突变也有活性。病例介绍一位 68 岁的妇女因淋巴结病和腹泻病史转诊,最终被发现患有全身性肥大细胞增多症,骨髓、胃肠道、肝脏和脾脏均受累。骨髓活检结果显示,她的 KIT 第 17 号外显子发生了 p.D816-N822delinsMIDSI 突变。患者开始服用阿伐替尼后,腹泻次数明显减少,胰蛋白酶水平显著下降。她的病程因关节痛而变得复杂,导致阿伐替尼剂量减少,最终出现脱颗粒发作,需要住院治疗。结论我们报告了一例侵袭性系统性肥大细胞增多症患者,其外显子17上存在新型KIT突变,阿伐替尼治疗后可获得持续应答。虽然阿伐替尼是一种针对 D816V 突变的强效抑制剂,但我们的病例表明,它对全身性肥大细胞增多症中其他罕见的 KIT 突变也可能有效,这为罕见突变患者提供了更多潜在的治疗选择。
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来源期刊
Leukemia Research Reports
Leukemia Research Reports Medicine-Oncology
CiteScore
1.70
自引率
0.00%
发文量
70
审稿时长
23 weeks
期刊最新文献
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