Annotation Detail
Information
- Associated Genes
- ABL1
- Associated Variants
-
ABL1 MUTATION
ABL1 MUTATION - Associated Disease
- chronic myeloid leukemia
- Source Database
- CIViC Evidence
- Description
- In this open-label, phase II registration trial, patients that were imatinib resistant (n = 192) or intolerant (n = 89) underwent nilotinib monotherapy. Prior to nilotinib treatment, 105 and 9 patients with baseline BCR-ABL mutations were imatinib resistant and intolerant, respectively. Within 12 months of therapy, among patients with baseline mutations, complete hematologic response was achieved in 57 (71%) of 80 [vs. 35 (80%) of 80 Abl1 wildtype patients, P = .393], major cytogenetic response in 49 of 100 [vs. 52 (60%) of 87, P = .145], complete cytogenetic response in 32 of 100 [vs. 35 (40%) of 87, P = .285], and major molecular response in 19 (22%) of 87 [vs. 22 (29%) of 76, P = .366]. These data shows no significant difference in nilotinib efficacy between patients with baseline mutations in the Abl1 kinase domain versus without. The authors observe clinical efficacy of nilotinib for many of the 29 variants found and identify only Y253H, E255K/V, and F359C/V as resistance conferring variants with IC50 greater than 150 nM. Individuals with T315I variants (3% of total population) were excluded.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/6342
- Gene URL
- https://civic.genome.wustl.edu/links/genes/4
- Variant URL
- https://civic.genome.wustl.edu/links/variants/2371
- Rating
- 3
- Evidence Type
- Predictive
- Disease
- Chronic Myeloid Leukemia
- Evidence Direction
- Does Not Support
- Drug
- Nilotinib
- Evidence Level
- B
- Clinical Significance
- Resistance
- Pubmed
- 19652056
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Nilotinib | Resitance or Non-Reponse | false |