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KIT D816V is the mutation behind almost every case of systemic mastocytosis. It makes the disease resistant to imatinib, and it is detected by a highly sensitive blood PCR; avapritinib treats the disease whether or not the mutation is confirmed.
The exon 17 D816V substitution locks KIT in the active conformation and is present in over 90 percent of systemic mastocytosis, often at low allele burden requiring sensitive allele-specific PCR of blood or marrow. The FDA companion diagnostic list carries the ARUP KIT D816V Assay for imatinib in aggressive systemic mastocytosis (a humanitarian device exemption, H140006, 2015): imatinib is labelled for aggressive systemic mastocytosis without the D816V mutation or with unknown status, so the test selects patients by excluding D816V. Avapritinib's labels for advanced and indolent systemic mastocytosis do not require D816V testing; the mutation is also found in core-binding-factor AML and some GISTs where it confers imatinib resistance.
In plain words · KIT mutation is the driver behind most gastrointestinal stromal tumours, and the reason imatinib turned a sarcoma with a median survival of about a year into a chronic disease.
In systemic mastocytosis a KIT D816V result confirms the diagnosis and tells your team that imatinib will not work; avapritinib is the on-label targeted treatment and does not require the mutation to be shown. The mutation is often present in tiny amounts, so a negative result from an insensitive test should be repeated with a sensitive blood PCR.
Written only from the label or guideline text cited on this page. Not medical advice; your own report and the reading your team gives it come first.
The KIT c.2447A>T (p.D816V) substitution by allele-specific quantitative PCR or sequencing of blood or marrow; for imatinib the selecting result is its absence.
“KIT D816V Assay (ARUP Laboratories, Inc.): KIT D816V”
FDA: List of FDA-Authorized Companion Diagnostic Devices| Threshold | Drug | Cancer | Regulator | Source |
|---|---|---|---|---|
| D816V absent or unknown (negative selector for imatinib) Imatinib's label covers aggressive systemic mastocytosis without the D816V c-Kit mutation or with unknown mutational status. | Imatinib | Systemic mastocytosis | FDA | label |
| Device | Maker | Indication and sample | Drug | PMA / 510(k) |
|---|---|---|---|---|
| KIT D816V Assay | ARUP Laboratories | Aggressive Systemic Mastocytosis - Bone Marrow | Imatinib | H140006 (12/18/2015) |
Matched on the name and aliases of the readout in the title, setting and summary of each trial; a match is a mention, not proof the readout was an entry criterion.
Shares PDGFRA exon 18 mutation (D842V), Avapritinib, KIT, Gastrointestinal stromal tumour (GIST).
Shares On-target resistance mutations (gatekeeper, solvent-front, compound), Acute myeloid leukaemia and the tag biomarker.
Shares PDGFRA exon 18 mutation (D842V), Avapritinib, KIT, Gastrointestinal stromal tumour (GIST).
Shares PDGFRA exon 18 mutation (D842V), Avapritinib, KIT, Gastrointestinal stromal tumour (GIST).
Shares Acute myeloid leukaemia and the tag biomarker.
Shares Acute myeloid leukaemia and the tag biomarker.
Shares Avapritinib, Systemic mastocytosis.
Shares Imatinib and the tag biomarker.