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    Home > Active Ingredient News > Antitumor Therapy > Leukemia: Comprehensive clinical evaluation of Guadecitabine (SGI-110) in peripheral T-cell lymphoma

    Leukemia: Comprehensive clinical evaluation of Guadecitabine (SGI-110) in peripheral T-cell lymphoma

    • Last Update: 2022-05-26
    • Source: Internet
    • Author: User
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    Peripheral T-cell lymphoma (PTCL) is a rare, heterogeneous malignancy that relapses with poor patient outcomes
    .
    Previous studies have shown that PTCL has a high sensitivity to epigenetic-related targeted drugs
    .

    Peripheral T-cell lymphoma (PTCL) is a rare, heterogeneous malignancy that relapses with poor patient outcomes
    .
    Peripheral T-cell lymphoma (PTCL) is a rare, heterogeneous malignancy that relapses with poor patient outcomes
    .

    Hypomethylating agents (HMAs) are a class of epigenetic antineoplastic drugs that have been previously shown to have a role in PTCL, along with genetic mutations shared with myelodysplastic syndromes (MDS)
    .
    The researchers found that follicular helper T-cell-derived PTCL had an impressive response rate to azacitidine

    .


    Guadecitabine (SGI-110) is an oligonucleotide analog of decitabine that has been shown to be effective in MDS
    .
    In this study, the researchers mainly presented the results of a Phase II clinical trial of guadecitabine in PTCL
    .
    Correlation analysis and functional genomic screening of clinical data to better identify relevant epigenetic regulators

    .


    Guadecitabine (SGI-110) is an oligonucleotide analog of decitabine that has been shown to be effective in MDS
    .
    Guadecitabine (SGI-110) is an oligonucleotide analog of decitabine that has been shown to be effective in MDS
    .


    Summary table of patient response to treatment


    Summary table of patient response to treatment

     

    In this phase II, single-arm trial, patients with PTCL received guadecitabine on days 1-5 of a 28-day treatment cycle
    .
    The trial's primary endpoints were overall response rate (ORR) in patients and the drug's safety profile
    .
    Transformant studies include cell-free plasma DNA sequencing and functional genomic screening, and epigenetically targeted CRISPR/Cas9 libraries identify relevant response predictors

    .

    In this phase II, single-arm trial, patients with PTCL received guadecitabine on days 1-5 of a 28-day treatment cycle
    .
    In this phase II, single-arm trial, patients with PTCL received guadecitabine on days 1-5 of a 28-day treatment cycle
    .


    RESULTS: Among 20 relapsed/refractory patients, the ORR was 40%, of which 10% achieved complete remission
    .
    The most common grade 3-4 adverse events included neutropenia and thrombocytopenia
    .
    Patients were followed for a median of 10 months, during which median progression-free survival (PFS) and overall survival (OS) were 2.
    9 months and 10.
    4 months, respectively

    .


    Among 20 relapsed/refractory patients, the ORR was 40%, of which 10% achieved complete remission
    .
    Among 20 relapsed/refractory patients, the ORR was 40%, of which 10% achieved complete remission
    .


    Patient response graph


    Patient response graph

    Further studies showed that the RHOA G17V mutation was associated with improved PFS
    .
    Four out of seven patients with TP53 mutations responded to treatment

    .
    Deletion of the histone methyltransferase SETD2 showed sensitivity to HMA, but deletion of TET2 was not

    .


    In conclusion, the results of this study show that guadecitabine treatment has an acceptable overall response rate and drug toxicity profile, and the combination of decitabine analogs with a therapeutic strategy targeting histone methyltransferase may provide potential for the treatment of peripheral T-cell lymphoma.
    basis

    .


    Guadecitabine therapy has an acceptable overall response rate and drug toxicity profile, and a combination of decitabine analogs targeting histone methyltransferases may provide a potential basis for the treatment of peripheral T-cell lymphoma
    .
    Guadecitabine therapy has an acceptable overall response rate and drug toxicity profile, and a combination of decitabine analogs targeting histone methyltransferases may provide a potential basis for the treatment of peripheral T-cell lymphoma
    .


    Original source:


    Original source:

    Wong, J.
    , Gruber, E.
    , Maher, B.
    et al.
    Integrated clinical and genomic evaluation of guadecitabine (SGI-110) in peripheral T-cell lymphoma.
    Leukemia (22 April 2022).

    Wong, J.
    , Gruber, E.
    , Maher, B.
    et al.
    Integrated clinical and genomic evaluation of guadecitabine (SGI-110) in peripheral T-cell lymphoma.
    Leukemia (22 April 2022).

    https://doi.
    org/10.
    1038/s41375-022-01571-8

    https://doi.
    org/10.
    1038/s41375-022-01571-8


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