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Cutaneous T-Cell Lymphoma: Can Genetic Polymorphisms Help Select Patients for Treatment With Bexarotene?

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Key Points

  • During treatment with bexarotene, 82.7% of patients experienced hypertriglyceridemia, which was classified as severe or extreme in 8.3%
  • Patients who carried minor alleles of the polymorphisms did not show significant differences in baseline triglyceride concentrations.
  • After treatment with bexarotene, carriers of at least 1 of the 2 minor alleles of APOA5 c.-1131T>C and APOC3c.*40C>G showed lower levels of triglycerides than noncarriers.

Bexarotene is a retinoid approved for the treatment of patients with cutaneous T-cell lymphoma (CTCL) who have not responded to at least one previous treatment regimen. Hypertrigylceridemia is the most frequent adverse event related to treatment with bexarotene in CTCL. Even with prophylactic measures, there is a wide variability in the severity of adverse reactions to bexarotene.

Researchers sought to analyze the relationship between specific genetic polymorphisms and hypertriglyceridemia related to bexarotene therapy in an effort to see if the adverse event was associated with genetic and/or environmental factors. Their findings were published by Cabello et al in JAMA Dermatology.

Methods

The study group was comprised of 116 patients with confirmed CTCL who had received bexarotene for at least 3 months. Data on demographic and cardiovascular risk factors were collected, and a complete blood analysis—including lipid profile and genetic analysis—was performed. The mean age was 61.2; 59.5% of study participants were men, and 73.2% were diagnosed with mycosis fungoides.

The primary outcome measures were the maximal triglyceride levels reported in association with the minor alleles of the polymorphisms studied—the apolipoprotein genes APOA5APOC3, and APOE.

Findings

During treatment with bexarotene, 82.7% of patients experienced hypertriglyceridemia, which was classified as severe or extreme in 8.3%. Patients who carried minor alleles of the polymorphisms did not show significant differences in baseline triglyceride concentrations.

After treatment with bexarotene, carriers of at least one of the two minor alleles of APOA5 c.-1131T>C and APOC3c.*40C>G showed lower levels of triglycerides than noncarriers.

The researchers concluded, “These results indicate that the screening of APOA5 and APOC3 genotypes may be useful to estimate changes in triglyceride concentrations during bexarotene treatment in patients with CTCL and also to identify the best candidates for bexarotene therapy based on the expected adverse effect profile.”

Disclosure: The study authors' full disclosures can be found at jamanetwork.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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