Epstein-Barr virus reactivation in extranodal natural killer/T-cell lymphoma patients: a previously unrecognized serious adverse event in a pilot study with romidepsin.
Ann Oncol
; 27(3): 508-13, 2016 Mar.
Article
em En
| MEDLINE
| ID: mdl-26658891
ABSTRACT
BACKGROUND:
Romidepsin, a histone deacetylase (HDAC) inhibitor, has been approved for the treatment of relapsed and refractory peripheral T-cell lymphoma. However, the efficacy and safety of romidepsin has never been studied in patients with relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma (ENKTL). PATIENTS ANDMETHODS:
We conducted an open-label, prospective pilot study to evaluate the efficacy and feasibility of romidepsin in the treatment of patients with ENKTL. The treatment was intravenous infusion of romidepsin (14 mg/m(2)) for 4 h on days 1, 8, and 15 of a 28-day cycle, and was repeated until disease progression or the occurrence of unacceptable toxicity.RESULTS:
A total of five patients enrolled on to this pilot study. However, three patients developed fever and elevated liver enzyme and bilirubin levels immediately after their first administration of romidepsin. We suspected that these events were associated with Epstein-Barr virus (EBV) reactivation because of the rapidly elevated EBV DNA titers in blood from these patients. An in vitro study with the ENKTL cell line SNK-6 cells also showed that HDAC inhibitors including romidepsin increased the copy number of EBV DNA in a dose-dependent manner. These findings suggested that romidepsin-induced histone acetylation reversed the repressed state of the genes required for EBV reactivation and that romidepsin treatment may have caused EBV reactivation in EBV-infected tumor cells in ENKTL patients. Therefore, we discontinued the enrollment of patients into this pilot study.CONCLUSIONS:
Our study suggests that the use of romidepsin may cause severe EBV reactivation in patients with ENKTL.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ativação Viral
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Herpesvirus Humano 4
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Depsipeptídeos
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Linfoma Extranodal de Células T-NK
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Inibidores de Histona Desacetilases
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Antibióticos Antineoplásicos
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Ann Oncol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2016
Tipo de documento:
Article