Continuing medical education
Primary cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome): Part II. Prognosis, management, and future directions

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Both mycosis fungoides (MF) and Sézary syndrome (SS) have a chronic, relapsing course, with patients frequently undergoing multiple, consecutive therapies. Treatment is aimed at the clearance of skin disease, the minimization of recurrence, the prevention of disease progression, and the preservation of quality of life. Other important considerations are symptom severity, including pruritus and patient age/comorbidities. In general, for limited patch and plaque disease, patients have excellent prognosis on ≥1 topical formulations, including topical corticosteroids and nitrogen mustard, with widespread patch/plaque disease often requiring phototherapy. In refractory early stage MF, transformed MF, and folliculotropic MF, a combination of skin-directed therapy plus low-dose immunomodulators (eg, interferon or bexarotene) may be effective. Patients with advanced and erythrodermic MF/SS can have profound immunosuppression, with treatments targeting tumor cells aimed for immune reconstitution. Biologic agents or targeted therapies either alone or in combination—including immunomodulators and histone-deacetylase inhibitors—are tried first, with more immunosuppressive therapies, such as alemtuzumab or chemotherapy, being generally reserved for refractory or rapidly progressive disease or extensive lymph node and metastatic involvement. Recently, an increased understanding of the pathogenesis of MF and SS with identification of important molecular markers has led to the development of new targeted therapies that are currently being explored in clinical trials in advanced MF and SS.

Section snippets

Evaluation of a patient, staging, prognosis

Key points

  1. Patient evaluation requires a multidisciplinary team approach with dermatologists, oncologists, dermatopathologists, and radiation oncologists

  2. Staging of a patient requires an assessment of skin, lymph node, viscera, and blood involvement

  3. The prognosis of mycosis fungoides in most patients with limited patch/plaque disease is favorable and similar to that of an age-, sex-, and race-matched control population

Skin-directed therapies

Key points

  1. Topical corticosteroids are the most common treatment used in early mycosis fungoides and serve as an adjunct to other topical and systemic therapies at all stages

  2. Topical nitrogen mustard and phototherapy have similar efficacy in early stage mycosis fungoides with maintenance therapy needed for prolonged complete remissions

  3. Total skin electron beam therapy at a standard dose (30 Gy) is an effective treatment in refractory/relapsed extensive plaque and tumor mycosis fungoides associated with

Systemic therapies

Key points

  1. Single-agent systemic therapy (eg, bexarotene) is often used after skin-directed therapy is inadequate or in cases of advanced disease

  2. Immunomodulators, such as interferons and retinoids, are commonly used as first-line monotherapy in advanced mycosis fungoides and are also used in low-dose combination with topical agents

  3. Histone deactylase inhibitors (vorinostat or romidepsin) are also effective single agents in skin, nodal, and blood disease

  4. Alemtuzumab is particularly active in erythrodermic

Antifolates

The reduced folate carrier type 1, an oncofetoprotein that is predominantly expressed in the membranes of fetal and tumor cells, mediates the cellular uptake of folates and antifolate drugs, including methotrexate and a newer agent, pralatrexate (which is approved by the US Food and Drug Administration for relapsed/refractory peripheral T-cell lymphoma).161, 162 Both antifolates are substrates for folylpolyglutamate synthetase and potently inhibit dihydrofolate reductase.163

Low-dose

General health care

Key points

  1. Important quality of life considerations include pruritus, xerosis, and the prevention of skin infections

  2. Treatment-related toxicities may require dose adjustments, particularly in the elderly, patients with advanced disease, and patients with multiple comorbidities

Many patients are disabled by their pruritus and skin appearance. Emollients should be used for dryness and scaling, and the application of midpotency steroids, particularly triamcinolone 0.1% ointment once or twice daily, is

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    Conflicts of interest: None declared.

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