Low-Dose Bexarotene and Phototherapy or Interferon Alfa-2a in the Treatment of Patients with Relapsed or Refractory Cutaneous T-Cell Lymphoma
Authors: Beltran Brady , Paredes Antonio , Moises Celia , Sanchez Gadwin , Riva Luis , Hurtado Fernando , Salas Renzo , Castillo Jorge 
Published: April 2020

Abstract
Background: 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). Relapsed or refractory cases of CTCL have poor prognosis and are in need of safe and more effective therapies. Synergy between bexarotene and interferon or phototherapy has been previously described.
Objective: Report a Peruvian single-institution experience on eight cases of relapsed or refractory CTCL who were treated with low-dose bexarotene in combination with phototherapy or interferon alfa-2a.
Methods: From 2002 to 2007, eight patients with relapsed or refractory CTCL were treated with bexarotene 300 mg by mouth daily in combination with interferon alfa-2a 9 million units subcutaneously three times a week (five patients) or phototherapy (two patients received PUVA therapy and one patient received narrow-wave UVB therapy). Bexarotene, interferon and phototherapy were continuously administered until progression of disease or unacceptable toxicity. Five patients were diagnosed with mycosis fungoides (MF), two patients had aggressive epidermotropic CD8+ cytotoxic lymphoma (AECL) and one patient had Sezary Syndrome (SS).
Results: Mean age was 58 years (range 36 to 70). Patients were exposed to three prior lines of therapy in average (range 2 to 5). One patient had complete response, four patients had partial response and three patients experienced progressive disease. The overall response for the entire group was 62.5% with a mean duration of response of 20 months (range 7 to 67 months). Forty percent (2/5) of patients had partial response to the bexarotene and interferon combination; no complete responses were observed. The two responders, one patient with SS and one patient with MF, are alive 67 and 17 months, respectively. On the other hand, 100% (3/3) of patients responded to the bexarotene and phototherapy combination. A patient with stage I MF experienced a complete response and two patients had a partial response, one patient with MF and one with AECL. Of note, the patient who achieved a complete response was treated with bexarotene and narrow-wave UVB. Most commonly side effects observed were mild, five patients experienced grade 1–2 hypercholesterolemia, hypertriglyceridemia grade 1–2 was seen in four patients and grade 3 in one case. Two patients developed grade 1–2 hypothyroidism. Our patient with SS developed cardiomyopathy related to interferon after 17 months of therapy and continues on single-agent bexarotene. The use of bexarotene in the treatment of AECL has seldom been reported. We are also reporting one of the longest lasting responses described in a patient with SS treated with bexarotene.
Conclusions: Low-dose bexarotene in combination with phototherapy or interferon alfa-2a in the treatment of relapsed and refractory CTCL seems safe and effective. Further research is necessary to develop improved, more effective therapies.
Table 1. Characteristics of reported patients
Age Sex Histology Stage Number previous treatments Treatment Response Duration response (months) Bexarotene/interferon Bexarotene/phototherapy F: female; M: male; SS: Sezary syndrome; AECL: aggressive epidermotropic CD8+ cytotoxic lymphoma; MF: mycosis fungoides; PR: partial response; CR: complete response; PD: progressive disease 69 F SS - 2 X PR 67 61 M MF III 2 X PR 17 36 F AECL IB 4 X PD - 70 F MF IIB 2 X PD - 57 M MF IIB 5 X PD - 44 M MF IB 2 X CR 17 59 M MF IIB 2 X PR 7 67 M AECL IIB 3 X PR 12