Annotation Detail

Information
Associated Genes
NTRK3
Associated Variants
NTRK3 ETV6-NTRK3
Associated Disease
B-cell adult acute lymphocytic leukemia
Source Database
CIViC Evidence
Description
61-year-old man is diagnosed with B-ALL. While an initial analysis detected the ETV6-NTRK3 fusion, it was at a low count and it was decided that it was not the main oncogene. Initial therapies included chemotherapy and CAR-T infusion. Relapse after these therapies found a large increase in fusion transcripts and NTRK3 rearrangements were detectable by FISH in 50/50 blast nuclei. Patient was treated with oral monotherapy larotrectinib (100mg twice per day). After 4 days on treatment peripheral blood blasts become undetectable; after 6 days on treatment lymphadenopathy and leukemia cutis resolved and a biopsy revealed an ablated bone marrow with only a few scattered blasts. Patient experience clinical benefit with no apparent side effects during 42 days of larotrectinib treatment, however, patient eventually succumbed to multifocal angioinvasive aspergillosis. Later sequencing of the NTRK3 kinase domain did not detect any larotrectinib resistance mutations (p.G623R, p.G696A).
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/7993
Gene URL
https://civic.genome.wustl.edu/links/genes/3985
Variant URL
https://civic.genome.wustl.edu/links/variants/801
Rating
3
Evidence Type
Predictive
Disease
B-cell Adult Acute Lymphocytic Leukemia
Evidence Direction
Supports
Drug
Larotrectinib
Evidence Level
C
Clinical Significance
Sensitivity/Response
Pubmed
31905241
Drugs
Drug NameSensitivitySupported
LarotrectinibSensitivitytrue