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    Association details:
    Biomarker:TP53 mutation
    Cancer:Acute Myelogenous Leukemia
    Drug:cytarabine (DNA synthesis inhibitor, DNA-directed DNAP inhibitor)
    Direction:Resistant
    Evidence:
    Evidence Level:
    Sensitive: C2 – Inclusion Criteria
    New
    Source:
    clinicaltrials.gov
    Title:

    Study of MK-8242 Alone and in Combination With Cytarabine in Participants With Acute Myelogenous Leukemia (P07649)

    Excerpt:
    ...and have wild type p53 gene mutation analysis...
    Trial ID:
    NCT01451437
    Evidence Level:
    Resistant: C3 – Early Trials
    Source:
    EHA 2021
    Title:

    THE IMPACT OF MUTATIONAL LOAD (VAF) DETECTED IN THE TP53, EZH2, U2AF1, WT1, FLT3 AND SF3B1 GENES WAS IDENTIFIED AS AN INDEPENDENT PROGNOSTIC MARKER FOR OS OR RFS IN A COHORT OF 497 CASES WITH AML

    Published date:
    05/12/2021
    Excerpt:
    The mutational profile at diagnosis was identified by NGS (Ion Torrent System), using a panel of 41 genes involved in myeloid pathologies...TP53….Finally, in patients treated with low-dose cytarabine, TP53 is associated with worse OS and a higher mutational load of TP53 or mutations in the BCOR gene are associated with a worse RFS.
    Evidence Level:
    Resistant: C3 – Early Trials
    Source:
    Blood Adv
    Title:

    Prognostic and therapeutic impacts of mutant TP53 variant allelic frequency in newly diagnosed acute myeloid leukemia

    Published date:
    11/19/2020
    Excerpt:
    CONTRADICTING EVIDENCE: We retrospectively analyzed 202 patients with newly diagnosed TP53-mutated AML who underwent first-line therapy with either a cytarabine- or hypomethylating agent (HMA)-based regimen...The best long-term outcomes were observed in those with 1 TP53 mutation with VAF ≤40% who received a frontline cytarabine-based regimen (2-year OS, 38% vs 6% for all others; P < .001).
    DOI:
    10.1182/bloodadvances.2020003120
    Evidence Level:
    Resistant: C3 – Early Trials
    Source:
    ASH 2020
    Title:

    1911 Distinct Clinical and Genetic Factors Predict Early Versus Late Mortality in AML Patients Undergoing Induction Chemotherapy

    Published date:
    11/04/2020
    Excerpt:
    We identified 290 consecutive adult patients treated with standard induction chemotherapy (“7+3” with cytarabine and an anthracycline, or CPX-351) for newly diagnosed AML...the presence of TP53 mutation, U2AF1 mutation, or 11q23 rearrangement were independently associated with inferior OS after day 60, whereas the presence of CBF rearrangement was independently associated with superior OS after day 60...