U.S. flag

An official website of the United States government

GTR Home > Conditions/Phenotypes > Belinostat response

Summary

Belinostat is a histone deacetylase (HDAC) inhibitor, approved for the treatment of relapsed or refractory peripheral T-cell lymphomas (PTCLs). Belinostat targets 3 classes of HDACs (I, II and IV), resulting in higher levels of acetylation of both histone and non-histone proteins, thus reversing the changes in protein acetylation that are frequently disrupted during oncogenesis. Belinostat is administered as an infusion at a rate of 1000 mg/m2 for 30 minutes on days 1–5 of a 21-day cycle. Belinostat has a relatively short half-life and is primarily metabolized by uridine diphosphate (UDP)-glucuronosyltransferase 1A1 (UGT1A1)-mediated glucuronidation, with minor contributions from other UGT and cytochrome P450 (CYP) enzymes. Genetic variation at the UGT1A1 locus can result in decreased enzyme activity and thus increased exposure to belinostat. The US Food and Drug Administration (FDA)-approved drug label recommends a 25% decrease in dose for individuals who are known to be homozygous for the UGT1A1*28 reduced function allele. Additional indications for dose reduction include grade 3 or 4 adverse reactions or significant decrease in neutrophil or platelet counts following belinostat administration. Some studies have suggested that other variant alleles may also lead to increased belinostat exposure, such as UGT1A1*60; however, no specific recommendations for dose reduction have been made for these alleles by either the FDA or other professional pharmacogenetic consortia. Belinostat should not be administered with other medications that can inhibit UGT1A1 function, such as nilotinib, ketoconazole, or ripretinib. [from Medical Genetics Summaries]

Genes See tests for all associated and related genes

  • Also known as: BILIQTL1, GNT1, HUG-BR1, UDPGT, UDPGT 1-1, UGT1, UGT1A, UGT1A1
    Summary: UDP glucuronosyltransferase family 1 member A1

Therapeutic recommendations

From Medical Genetics Summaries

This section contains excerpted1information on gene-based dosing recommendations. Neither this section nor other parts of this review contain the complete recommendations from the sources.

2023 Statement from the US Food and Drug Administration (FDA):

Patients with Reduced UGT1A1 Activity

Reduce the starting dose of Beleodaq to 750 mg/m2 in patients known to be homozygous for the UGT1A1*28 allele.

[….]

Pharmacogenomics

UGT1A1 activity is reduced in individuals with genetic polymorphisms that lead to reduced enzyme activity such as the UGT1A1*28 polymorphism. Approximately 20% of the black population, 10% of the white population, and 2% of the Asian population are homozygous for the UGT1A1*28 allele. Additional reduced function alleles may be more prevalent in specific populations.

Because belinostat is primarily (80 -90%) metabolized by UGT1A1, the clearance of belinostat could be decreased in patients with reduced UGT1A1 activity (e.g., patients with UGT1A1*28 allele). Reduce the starting dose of Beleodaq to 750 mg/m2 in patients known to be homozygous for the UGT1A1*28 allele to minimize dose limiting toxicities.

Please review the complete therapeutic recommendations that are located here: (1)

1The FDA labels specific drug formulations. We have substituted the generic names for any drug labels in this excerpt. The FDA may not have labeled all formulations containing the generic drug. Certain terms, genes and genetic variants may be corrected in accordance to nomenclature standards, where necessary. We have given the full name of abbreviations, shown in square brackets, where necessary.

Practice guidelines

Consumer resources

IMPORTANT NOTE: NIH does not independently verify information submitted to the GTR; it relies on submitters to provide information that is accurate and not misleading. NIH makes no endorsements of tests or laboratories listed in the GTR. GTR is not a substitute for medical advice. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.