Interferon and Low Dose Methotrexate Improve Outcome in Refractory Mycosis Fungoides/Sézary Syndrome

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.

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“…58 In this study, the median weekly dose was 25 mg with maximum doses up to 75 mg. Low-dose MTX has been successfully combined with IFN-␣. 60 …”

Section: Low-dose Mtxmentioning

confidence: 99%

How I treat mycosis fungoides and Sézary syndrome

Prince

Whittaker

Hoppe

2009

Blood

135

109

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“…This combination is effective for advanced MF/SS; 74% complete response rate at 1 year among subjects with advanced CTCL (stage IIB-IVB). 34 …”

Section: Other Agent Rationalementioning

confidence: 99%

“…30 Higher doses of MTX are sometimes used (for example, 10 mg/m 2 biweekly in combination with alphainterferon [IFN-a]). 34 LyP is often quite sensitive to MTX and sometimes responds well to weekly doses as low as 5 mg. Oral folic acid supplementation (1-5 mg daily) ameliorates GI symptoms 35 ; however, the dose or dosing of folic acid might affect efficacy.…”

Section: Typical Dosingmentioning

confidence: 99%

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Methotrexate and Pralatrexate

Wood

2015

Dermatologic Clinics

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This article reviews methotrexate and the more potent, related compound, pralatrexate, for the treatment of cutaneous T-cell lymphomas, including mycosis fungoides, Sézary syndrome, and CD30+ lymphoproliferative disorders. Although these folate antagonists are traditionally viewed as antiproliferative cell cycle inhibitors, it is recognized that they inhibit DNA methylation, providing a rationale for their use as epigenetic regulators and cell proliferation inhibitors. The underlying mechanisms are outlined, key supporting data presented, followed by brief mention of recent mathematical modeling supporting the general superiority of combination therapy. Several novel examples involving folate antagonists are proposed.

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“…48 Low-dose MTX has also been successfully combined with IFN-a. 49 Cutaneous lymphomas are highly radiosensitive and radiotherapy is a key palliative therapy for MF especially for sanctuary sites resistant to phototherapy. 50 Partial regression of disease may be observed with single doses as low as 1.0 Gy 51 and single doses as low as 8 Gy achieve a CR rate of 94.4%.…”

mentioning

confidence: 99%

How I treat mycosis fungoides and Sézary syndrome

Prince

Whittaker

Hoppe

2016

Blood

145

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Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma variant and is closely related to a rare leukemic variant, Sézary syndrome (SS). MF patients at risk of disease progression can now be identified and an international consortium has been established to address the prognostic relevance of specific biologic factors and define a prognostic index. There are a lack of randomized clinical trial data in MF/SS and evidence is based on a traditional “stage-based” approach; treatment of early-stage disease (IA-IIA) involves skin directed therapies which include topical corticosteroids, phototherapy (psoralen with UVA or UVB), topical chemotherapy, topical bexarotene, and radiotherapy including total skin electron beam therapy. Systemic approaches are used for refractory early-stage and advanced-stage disease (IIB-IV) and include bexarotene, interferon α, extracorporeal photopheresis, histone deacetylase inhibitors, and antibody therapies such as alemtuzumab, systemic chemotherapy, and allogeneic transplantation. However, despite the number of biologic agents available, the treatment of advanced-stage disease still represents an unmet medical need with short duration of responses. Encouragingly, randomized phase 3 trials are assessing novel agents, including brentuximab vedotin and the anti-CCR4 antibody, mogamulizumab. A broader understanding of the biology of MF/SS will hopefully identify more effective targeted therapies.

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Interferon and Low Dose Methotrexate Improve Outcome in Refractory Mycosis Fungoides/Sézary Syndrome

Cited by 35 publications

References 13 publications

How I treat mycosis fungoides and Sézary syndrome

How I treat mycosis fungoides and Sézary syndrome

Methotrexate and Pralatrexate

How I treat mycosis fungoides and Sézary syndrome

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