How I treat mycosis fungoides and Sézary syndrome

Abstract

The most common subtypes of primary cutaneous T-cell lymphomas are mycosis fungoides (MF) and Sézary syndrome (SS). The majority of patients have indolent disease; and given the incurable nature of MF/SS, management should focus on improving symptoms and cosmesis while limiting toxicity. Management of MF/SS should use a “stage-based” approach; treatment of early-stage disease (IA-IIA) typically involves skin directed therapies that include topical corticosteroids, phototherapy (psoralen plus ultraviolet A radiation or ultraviolet B radiation), topical chemotherapy, topical or systemic bexarotene, and radiotherapy. Systemic approaches are used for recalcitrant early-stage disease, advanced-stage disease (IIB-IV), and transformed disease and include retinoids, such as bexarotene, interferon-α, histone deacetylase inhibitors, the fusion toxin denileukin diftitox, systemic chemotherapy including transplantation, and extracorporeal photopheresis. Examples of drugs under active investigation include new histone deacetylase inhibitors, forodesine, monoclonal antibodies, proteasome inhibitors, and immunomodulatory agents, such as lenalidomide. It is appropriate to consider patients for novel agents within clinical trials if they have failed front-line therapy and before chemotherapy is used.

Cutaneous T‐cell lymphoma: 2011 update on diagnosis, risk‐stratification, and management

“…The concise treatment algorithm provided in Fig. 2 is consistent with published treatment guidelines and expert opinion [199][200][201][202][203][204].…”

“…Therefore, patients with limited-stage disease who require therapy are best approached with skin-directed therapies, usually under the direction of a dermatologist and/or radiation oncologist. Excellent reviews, and treatment guidelines, are available [199][200][201][202][203][204]. Consequently, management of limited-stage disease will be summarized only briefly.…”

“…Multiple chemotherapeutic agents, including single-agent and combination chemotherapy regimens, are associated with high response rates in MF/SS and have been reviewed recently [200,202,332]. While combination chemotherapy regimens (e.g., CHOP) are associated with response rates exceeding 70-80%, the responses achieved are frequently short-lived and are associated with significant myelosuppression and infectious complications [333][334][335].…”

COX-2 is a novel target in therapy of mycosis fungoides

“…In fact, the effect of celecoxib appeared to be more pronounced than that of vorinostat (an HDAC inhibitor recently approved by the Food and Drug Administration for treatment of refractory CTCL) when used in the same xenotransplantation model. 2 Given an ectopic expression of COX-2 in malignant T cells in patients with advanced MF, our findings suggest that COX-2 is a novel therapeutic target in advanced MF. Because celecoxib is already approved for several non-malignant diseases and displays limited side effects, 8 this drug could provide a novel, nonaggressive option for treatment of patients with advanced MF.…”

“…Accordingly, there is a great need to develop novel targeted therapies and combination therapy for the treatment of refractory and advanced MF. 2 The etiology of MF is largely unknown, but numerous signaling pathways have been demonstrated to be involved in disease development and progression. A pathological dysregulation of the janus kinase (Jak)/signal transducer and activators of transcription (Stat) signaling axis has been detected in the majority of patients as well as a constitutive activation of other transcription factors such as NF-kB, c-Fos, c-Jun or c-Myc.…”