Real-world cardiovascular safety profile of bexarotene for the treatment of mycosis fungoides

Bexarotene has been established as an effective therapeutic agent for mycosis fungoides (MF), both in early, refractory disease and in advanced stages. It has a predictable, albeit significant, metabolic toxicity profile, raising concerns regarding long-term cardiovascular safety. We conducted a retrospective cohort study utilizing TriNetX to identify adults with MF. Patients were stratified by bexarotene exposure and 1:1 propensity score matched (PSM) for demographics, lifestyle factors, comorbidities, and baseline medications. After PSM, two well-balanced cohorts of 2,242 patients each were formed with a median follow-up of 4.0 years for both groups. Bexarotene treatment demonstrated no significant increase in the risk of the composite adapted-MACE endpoint (HR = 0.93, 95% CI: 0.78-1.11, p = 0.425). Similarly, no significant differences were observed for individual cardiovascular components, including acute myocardial infarction (HR = 0.95, p = 0.730), stroke (HR = 0.90, p = 0.514), or heart failure (HR = 0.93, p = 0.455). Conversely, bexarotene was associated with a significantly increased risk of metabolic and endocrine abnormalities, including hypertriglyceridemia (RR = 6.98, p < 0.001), hypothyroidism (RR = 4.93, p < 0.001), hyperlipidemia (RR = 2.18, p < 0.001), and hypercholesterolemia (RR = 1.99, p < 0.001). In the largest real-world cohort of MF patients treated with bexarotene to date, the substantial metabolic and endocrine abnormalities associated with treatment did not translate into an observed increase in cardiovascular events during a median follow-up of 4 years. These findings provide reassurance regarding the short- to intermediate-term cardiovascular profile of bexarotene when appropriate monitoring and management of lipid and thyroid abnormalities are maintained. However, longer follow-up is required to determine whether these metabolic effects influence long-term cardiovascular risk.