Low-Dose Bexarotene Alone or in Combination for the Treatment of Relapsed or Refractory Cutaneous T-Cell Lymphoma.

Selective ligands of retinoid X receptor (i.e. bexarotene) are used in the treatment of early and advanced stages of cutaneous T-cell lymphoma (CTCL). The objective of this study is to report a Peruvian single-institution experience on 13 cases of relapsed or refractory CTCL who were treated with low-dose bexarotene alone or in combination with phototherapy or interferon alfa-2a.

From 2002 to 2008, thirteen patients with relapsed or refractory CTCL were treated with bexarotene at low dose (75-300 mg/day) as monotherapy (BEX; 3 cases) or in combination with interferon alfa-2a (INF) at 3-9 million units subcutaneously three times a week (5 cases) or phototherapy (PT; 4 cases). Therapy was continuously administered until progression of disease or unacceptable toxicity. Eight patients with mycosis fungoides (MF), two patients with aggressive epidermotropic CD8+ cytotoxic lymphoma (AECL), two patients with Sezary Syndrome (SS) and one with smoldering adult T-cell leukemia/lymphoma (ATLL) were included in this study.

Mean age was 57 years (range 26 to 74 years). In average, patients were exposed to three prior lines of therapy (range 1 to 5). From the 8 cases of MF, 3 cases were treated with BEX monotherapy, achieving 1 complete response (CR), 1 partial response (PR) and 1 progressive disease (PD); 3 cases were treated with BEX and PT, obtaining 1 CR and 2 PR; and 2 cases were treated with BEX and IFN, both showing PD. From the 2 cases with AECL, 1 case received BEX/PT achieving a PR and 1 case received BEX/IFN showing PD. From the 2 cases with SS, both were treated with BEX/IFN achieving a PR. The case of ATLL achieved a PR with BEX/PT. The overall response for the entire group was 69.2% (9/13) with a mean duration of response of 15 months (range 2 to 67 months). From the therapy point of view, BEX alone achieved a 66% overall response rate (ORR), BEX/IFN showed a 40% ORR and BEX/PT showed a 100% ORR with a 20% CR. Most common adverse events were mild, seven patients experienced grade 1–2 hypercholesterolemia, and hypertriglyceridemia grade 1–2 was seen in seven patients and grade 3 in two cases. Four patients developed grade 1–2 hypothyroidism.

Low-dose BEX alone or in combination with INF or PT is effective in the treatment of patients with relapsed or refractory CTCL and is associated with mild toxicity. Prospective studies, if possible, are needed to further investigate novel therapeutic approaches in these hard-to-treat patients.

No relevant conflicts of interest to declare.