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    Home > Active Ingredient News > Blood System > Leukemia: Efficacy and Safety of Guadecitabine in Patients with Peripheral T-Cell Lymphoma

    Leukemia: Efficacy and Safety of Guadecitabine in Patients with Peripheral T-Cell Lymphoma

    • Last Update: 2022-05-22
    • Source: Internet
    • Author: User
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    Peripheral T-cell lymphoma (PTCL) is a rare, heterogeneous malignancy with an extremely poor prognosis when it relapses
    .
    Fortunately, the latest findings suggest that PTCL is more sensitive to epigenetic targeting drugs

    .
    The hypomethylating agent (HMA) azacitidine has significant efficacy in multiple myeloma (MDS, an HMA-responsive disease)

    .
    Based on the overlapping mutational spectrum of PTCL and MDS, azacitidine has also shown promising efficacy in PTCL patients

    .

    Guadecitabine, a decitabine analog, has shown good efficacy in MDS patients
    .
    The researchers speculate that patients with PTCL may also benefit from treatment with guadecitabine

    .

    This study is a single-center Phase II clinical trial recruiting patients 18 years of age and older with an ECOG performance status of ≤3, histologically diagnosed, treatment-naïve, or relapsed/refractory PTCL, treated with Treatment with citabine (60 mg/m2) on days 1-5/28 until disease progression
    .
    The primary endpoints were overall response rate (ORR) and safety

    .


    Progression-Free Survival and Overall Survival


    progression

    -free survival and overall survival

    A total of 20 patients (two were treatment-naïve and 18 were relapsed/refractory PTCL) were recruited between June 2018 and January 2020
    .
    With a median follow-up of 10 months,
    the overall response rate was 40%, including 10% complete response
    .
    The median progression-free survival (PFS) and overall survival (OS) were 2.
    9 months and 10.
    4 months, respectively

    .
    The most common grade 3-4 adverse reactions were neutropenia and thrombocytopenia

    .

    The overall response rate was 40%, including 10% complete response The overall response rate was 40%, including 10% complete response


    Mutation spectrum of ctDNA in test patients


    Mutation spectrum of ctDNA of

    test patient Mutation spectrum of ctDNA of test patient

    In an exploratory analysis, RHOAG17V mutation was associated with prolonged progression-free survival (median time: 5.
    47 vs 1.
    35 months, p=0.
    02)

    .
    Four out of seven patients with TP53 mutations achieved remission

    .
    Loss of the histone methyltransferase SETD2 increases sensitivity to HMA, but not TET2

    .

    RHOAG17V mutation is associated with prolonged progression-free survival

    In conclusion, Guadecitabine demonstrated acceptable overall response rates and toxicity profiles in patients with peripheral T-cell lymphoma ; decitabine analogs may be promising candidates for future combined targeting of histone methyltransferases.
    Joint programmes provide the basis

    .

    Guadecitabine demonstrated acceptable overall response rate and toxicity profile in patients with peripheral T-cell lymphoma Guadecitabine demonstrated acceptable overall response rate and toxicity profile in patients with peripheral T-cell lymphoma Overall response rate and toxicity profile

     

    Original source:

    Original Source: Original Source:

    Wong Jonathan, Gruber Emily, Maher Belinda et al.
    Integrated clinical and genomic evaluation of guadecitabine (SGI-110) in peripheral T-cell lymphoma.
    [J] .
    Leukemia, 2022, https://doi.
    org/10.
    1038/s41375- 022-01571-8

    Wong Jonathan, Gruber Emily, Maher Belinda et al.
    Integrated clinical and genomic evaluation of guadecitabine (SGI-110) in peripheral T-cell lymphoma.
    [J] .
    Leukemia, 2022, https://doi.
    org/10.
    1038/s41375- 022-01571-8


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