Reference Detail

Ref Type

PMID

(38273969)

Authors

Sandow L, Town A, Heinrich MC

Title

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

Journal	Vol	Issue	Date	Pages	Journal Short Title
Leukemia research reports	21		2024	100409	Leuk Res Rep

URL

Abstract Text

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.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.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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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance
KIT	D816_N822delinsMIDSI	indel	unknown	KIT D816_N822delinsMIDSI results in a deletion of seven amino acids in tyrosine kinase domain region 2 (exon 17) of the Kit protein from amino acids 816 to 822, combined with the insertion of five amino acids at the same site (PMID: 17555444). D816_N822delinsMIDSI has been identified in the scientific literature (PMID: 38273969), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Nov 2024).

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
KIT D816_N822delinsMIDSI	systemic mastocytosis	predicted - sensitive	Avapritinib	Case Reports/Case Series	Actionable	In a clinical case study, Ayvakit (avapritinib) treatment resulted in improved symptoms, reduced tryptase levels, and reduced lymphadenopathy in a patient with systemic mastocytosis harboring KIT D816_N822delinsMIDSI (PMID: 38273969).	38273969