Identifying Best Candidates for Bexarotene Therapy in Cutaneous T-Cell Lymphoma: Role of APOA5, APOC3 Genotypes

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Screening for APOA5 and APOC3 polymorphisms may help physicians who treat patients with cutaneous T-cell lymphoma identify the best candidates for bexarotene treatment.

According to results of a retrospective, observational, noninterventionalist, multicenter Spanish case-series study designed to evaluate the role played by genetic polymorphisms in bexarotene-treated patients with cutaneous T-cell lymphoma (CTCL), screening of the APOA5 and APOC3 genotypes in these individuals may be a useful tactic for estimating triglyceride concentrations. Findings from the current analysis were published in JAMA Dermatology.

The investigators sought to examine the link between genetic polymorphisms of apolipoprotein genes APOA5, APOC3, and APOE, and to evaluate the severity of hypertriglyceridemia among patients with CTCL receiving bexarotene therapy, as well as to optimize patient selection for treatment with bexarotene, based on the expected adverse effect profile.

The case series was performed at 12 university hospital dermatology departments in Spain between September 17, 2014, and February 17, 2015. A total of 125 patients with a confirmed diagnosis of CTCL who had received bexarotene for ≥3 months were enrolled in the study. Ultimately, 9 individuals were excluded because of missing analytic triglyceride data; thus, the final study group comprised 116 patients.

Data on demographic and cardiovascular risk factors were obtained for all participants. In addition, a complete blood analysis was performed, including a lipid profile, along with a genetic analysis from a saliva sample. The primary study outcome was the maximal triglyceride levels that were reported in association with the minor alleles of the polymorphisms being analyzed.

The mean patient age was 61.2±14.7 years; 59.5% of the participants were men, and 73.2% had mycosis fungoides, the most prevalent type of CTCL. While undergoing bexarotene treatment, 82.8% (96 of 116) of the participants developed hypertriglyceridemia, which was considered to be severe or extreme in 8.3% (8 of 96) of these patients.

Those individuals who carried minor alleles of the polymorphisms did not demonstrate any significant differences in baseline triglyceride levels. After bexarotene treatment, however, carriers of ≥1 of the 2 minor alleles of APOA5 c.1131T>C and/or APOC3 c.*40C>G had significantly lower concentrations of triglycerides compared with noncarriers of these minor alleles (241.59±169.91 mg/dL vs 330.97±169.03 mg/dL, respectively; P =.02), and were thus less likely to experience severe hypertriglyceridemia.

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The researchers concluded that the findings from this study suggest that APO polymorphism investigation might prove beneficial in the clinical evaluation of bexarotene-induced hypertriglyceridemia in patients with CTCL and identification of the most suitable candidates for this treatment. Future studies aimed at exploring the sensitivity of these polymorphisms for predicting adverse outcomes to recognize which patients might need to discontinue treatment, or which will experience pancreatitis are warranted.

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Cabello I, Alia P, Pintó X, e al. Association of APOA5 and APOC3 genetic polymorphisms with severity of hypertriglyceridemia in patients with cutaneous T-cell lymphoma treated with bexarotene. JAMA Dermatol. 2018;154(12):1424-1431.