Avapritinib treatment of aggressive systemic mastocytosis with a novel KIT exon 17 mutation
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...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Leukemia Research Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213048923000493 |
| _version_ | 1797363819491622912 |
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| author | Lyndsey Sandow Ajia Town Michael C. Heinrich |
| author_facet | Lyndsey Sandow Ajia Town Michael C. Heinrich |
| author_sort | Lyndsey Sandow |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T16:26:26Z |
| format | Article |
| id | doaj.art-95e4a68de6c94be7908fd21089f7d09c |
| institution | Directory Open Access Journal |
| issn | 2213-0489 |
| language | English |
| last_indexed | 2024-03-08T16:26:26Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Leukemia Research Reports |
| spelling | doaj.art-95e4a68de6c94be7908fd21089f7d09c2024-01-07T04:31:42ZengElsevierLeukemia Research Reports2213-04892024-01-0121100409Avapritinib treatment of aggressive systemic mastocytosis with a novel KIT exon 17 mutationLyndsey Sandow0Ajia Town1Michael C. Heinrich2Oregon Health and Science University Knight Cancer Institute, Portland, OR, United StatesPortland VA Health Care System and Oregon Health and Science University Knight Cancer Institute, R&D-19 3710 SW US Veterans Hospital Road, Portland, OR 97239, United StatesPortland VA Health Care System and Oregon Health and Science University Knight Cancer Institute, R&D-19 3710 SW US Veterans Hospital Road, Portland, OR 97239, United States; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2213048923000493 |
| spellingShingle | Lyndsey Sandow Ajia Town Michael C. Heinrich Avapritinib treatment of aggressive systemic mastocytosis with a novel KIT exon 17 mutation Leukemia Research Reports |
| title | Avapritinib treatment of aggressive systemic mastocytosis with a novel KIT exon 17 mutation |
| title_full | Avapritinib treatment of aggressive systemic mastocytosis with a novel KIT exon 17 mutation |
| title_fullStr | Avapritinib treatment of aggressive systemic mastocytosis with a novel KIT exon 17 mutation |
| title_full_unstemmed | Avapritinib treatment of aggressive systemic mastocytosis with a novel KIT exon 17 mutation |
| title_short | Avapritinib treatment of aggressive systemic mastocytosis with a novel KIT exon 17 mutation |
| title_sort | avapritinib treatment of aggressive systemic mastocytosis with a novel kit exon 17 mutation |
| url | http://www.sciencedirect.com/science/article/pii/S2213048923000493 |
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