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
.
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
.
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).
, 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
org/10.
1038/s41375-022-01571-8
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