Evaluation of Alitretinoin for the Treatment of Mycosis Fungoides and Sézary Syndrome

Abstract

<b><i>Background:</i></b> Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphoma (CTCL). There is currently no cure for CTCL, and treatment is aimed at limiting disease progression. This study evaluated the efficacy and tolerability of alitretinoin in CTCL management. <b><i>Methods:</i></b> A retrospective, multicenter study was conducted on CTCL patients treated with alitretinoin as a primary agent or in combination with standard therapies. <b><i>Results:</i></b> Forty-eight patients with MF (<i>n</i> = 40) and SS (<i>n</i> = 8) with a median age of 59.7 years (±14.3) were eligible for study inclusion. Treatment response data were evaluated in 40 patients and safety in 42 patients. 40.0% of the patients had early-stage, 43.8% had advanced-stage CTCL, and in 16.7% of patients there was insufficient information for staging. 40.0% (16/40) of the patients achieved a complete or partial response, whereas 47.5% (19/40) achieved stable disease, 12.5% (5/40) had progressive disease, and there were no cases of disease relapses in responders. Both early and advanced stages of CTCL were responsive to alitretinoin as a primary or combined modality. Alitretinoin was well tolerated, and 64.3% (27/42) of patients did not report any side effects. The most commonly observed side effect was hypertriglyceridemia. <b><i>Conclusions:</i></b> This retrospective analysis supports the efficacy and safety of alitretinoin in clearing skin disease and preventing disease progression in CTCL as a monotherapy or in combination with standard therapies.

Alitretinoin in the treatment of cutaneous T‐cell lymphoma

“…This represents an economic and financial burden for health care systems. Previous retrospective studies investigating monotherapy with alitretinoin or in combination in MF and SS described overall response rates, including CR and PR, of 90% in a study including 11 patients and 40% in a study including 40 patients 18,20 . Based on our results, we observed a similar ORR of 37.2%, whereas our patients always received additional therapy with TCS.…”

“…In comparison, alitretinoin has a better safety profile with the most commonly described side effects being mild hypertriglyceridemia, headache, and cheilitis. Alhusayen et al describe no side effects with alitretinoin in 64.3% of patients, the remaining affected patients reported hypertriglyceridemia in 40% of cases, followed by headache (13.3%) and dermatitis (13.3%), among others 18 . This is in agreement with our study with 62.8% of the patient collective showing no side effects, 20% with hypertriglyceridemia, and 8.6% with mental disorders such as depression, which is a known adverse effect of retinoids 27 .…”

“…The EORTC recommends retinoids alone or in combination with other systemic therapies for the treatment of MF and SS in stages IA–IIA as second‐line therapy, and in stage IIB as first‐line therapy 23 . Bexarotene has been shown to be effective in clinical trials and is currently considered the only licensed retinoid for the treatment of CTCLs, however, it is not available in all countries (e.g., Canada) 18 . Furthermore, side effects are dose‐related and frequent, which may result in discontinuation of therapy 24 .…”

“…Nevertheless, efficacy is accompanied by significant side effects, especially at higher doses, such as hypertriglyceridaemia and hypothyroidism, which may require a reduction or interruption of therapy 17 . Also, bexarotene is not available in all markets (e.g., Canada), leading to the need for alternative treatment options 18 . Alitretinoin binds both RARs and RXRs and is known to have a more favorable safety profile compared with other vitamin A derivatives regarding mucocutaneous side effects and impairment of laboratory findings of serum cholesterol, triglycerides, and thyroid parameters 10 .…”

“…Alitretinoin binds both RARs and RXRs and is known to have a more favorable safety profile compared with other vitamin A derivatives regarding mucocutaneous side effects and impairment of laboratory findings of serum cholesterol, triglycerides, and thyroid parameters 10 . Several case reports, a small prospective investigation, and a nationwide retrospective review showed promising results with a low incidence of side effects of the retinoid alitretinoin in the treatment of CTCLs 18–20 . However, further studies are needed to demonstrate the effectiveness and safety of alitretinoin in the treatment of MF and SS.…”