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    Association details:
    Biomarker:WT1 mutation
    Cancer:Acute Myelogenous Leukemia
    Drug:Venclexta (venetoclax) (Bcl2 inhibitor)
    Direction:Resistant
    Evidence:
    Evidence Level:
    Sensitive: C2 – Inclusion Criteria
    New
    Source:
    clinicaltrials.gov
    Title:

    Azacitidine in Combination With Venetoclax Treatment for MRD Positive Post Allo-HSCT AML/MDS Patients

    Excerpt:
    ...MRD was positive after transplantation, MFC > 0.1% and / or fusion gene and gene mutation (WT1 > 0.6%, AML1-ETO > 0.4%, others >1%)....
    Trial ID:
    NCT04809181
    Evidence Level:
    Resistant: C3 – Early Trials
    Source:
    ASH 2020
    Title:

    332 Interim Analysis of the Phase 1b/2 Study of the BCL-2 Inhibitor Venetoclax in Combination with Standard Intensive AML Induction/Consolidation Therapy with FLAG-IDA in Patients with Newly Diagnosed or Relapsed/Refractory AML

    Published date:
    11/04/2020
    Excerpt:
    100% of patients with KMT2A rearrangements (N=7), and 50% of patients with extra-medullary AML (N=4) achieved a CRc. In R/R AML, mutations in tumor suppressor (TS) genes (TP53, WT1, PHF6) were more frequently identified in patients without response (66% vs. 19%, p-value: 0.014) while 100% of R/R patients with NPM1 mutated AML achieved CRc.
    Secondary therapy:
    FLAG-IDA
    Evidence Level:
    Resistant: C3 – Early Trials
    Source:
    ASH 2018
    Title:

    Biomarkers Predicting Venetoclax Sensitivity and Strategies for Venetoclax Combination Treatment

    Published date:
    11/01/2018
    Excerpt:
    CONTRADICTING EVIDENCE...we observed that AML samples harboring PML-RARA translocations, WT1, and FLT3 with IDH1 mutations are more sensitive to venetoclax, and samples with TET2, KRAS, PTPN11 and SF3B1 mutations are more resistant.
    DOI:
    https://doi.org/10.1182/blood-2018-175
    Evidence Level:
    Resistant: C4 – Case Studies
    Source:
    Medicine (Baltimore)
    Title:

    Venetoclax + hypomethylating agents combined with dose-adjusted HAG for relapsed/refractory acute myeloid leukemia

    Published date:
    11/20/2020
    Excerpt:
    CONTRADICTING EVIDENCE: A 23-year-old man...The MRD result was 21.25%, and WT1 mutation was found in 15.38% of cells. On February 18, 2019, “venetoclax + aza” (venetoclax 100 mg/day increased daily to 400 mg/daily for maintenance, azacytidine 100 mg D3–9) chemotherapy was given. On March 9, the “hag” (homoharringtonine 2 mg × 7 days, cytarabine 100 mg q12 h × 7 days, GSF) scheme was added...No leukemic cells were found in the lumbar puncture on April 13...The progression-free survival was 2 months, and the overall survival time was 47 months...In summary, “venetoclax + HMAs combined with dose-adjusted CAH/HAG” is an effective method for adult R/RAML that has clinical value.
    Secondary therapy:
    HAG + azacitidine
    DOI:
    10.1097/MD.0000000000023265