Retinoids are natural and synthetic vitamin A analogs with effects on cell proliferation, differentiation, and apoptosis. They have significant activity in hematologic malignancies and have been studied extensively in cutaneous T-cell lymphoma. Retinoids bind to nuclear receptors and exert their effects through moderation of gene expression. Retinoic acid receptor and retinoic X receptor exert regulatory activity in vivo, binding to distinct ligands. Studies investigating systemic retinoids as monotherapy and in combination with other agents active against cutaneous lymphoma are reviewed. Side effects associated with retinoids include teratogenicity, dyslipidemias, and hypothyroidism, which should be carefully monitored in patients receiving treatment.
Key points
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Mycosis fungoides and Sézary syndrome subtypes of cutaneous T-cell lymphoma (CTCL) have a variable clinical course, ranging from indolent disease that does not alter life expectancy to aggressive, rapidly progressive disease.
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Goals of treatment, especially in patients with early-stage disease, are to induce remission with agents that have a low toxicity profile. The systemic retinoids are an important component of the treatment options for all stages of this disease because of the ease of administration and relatively low toxicity profile.
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Bexarotene is the only systemic retinoid approved by the Food and Drug Administration specifically for CTCL but does require additional medications to treat the associated hyperlipidemia and hypothyroidism during the duration of bexarotene treatment.
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Combination treatment with retinoids and other agents with activity against mycosis fungoides/Sézary syndrome appear to be well tolerated and associated with high response rates in relapsed or treatment refractory patients in small studies and series.
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