New systemic treatment options in mycosis fungoides and Sézary syndrome

Summary Cutaneous T cell lymphomas (CTCL) are a heterogeneous group of rare non-Hodgkin lymphomas. The most common type of CTCL is Mycosis fungoides (MF). Much less common but clinically and histopathologically related to MF is Sézary syndrome (SS). CTCL are incurable and associated with a reduced quality of life. While early stage MF has a good prognosis and is usually treated with skin directed therapies, advanced-stages require systemic therapies, including retinoids, interferon, cytotoxic chemotherapeutic drugs, low-dose methotrexate, histone deacetylase inhibitors and alemtuzumab. However, relapses are frequent and long-term remissions are achieved only in few cases, e.g. with allogenic stem cell transplantation. In recent years, new therapeutic options have evolved by the approval of brentuximab vedotin and mogamulizumab. Both recently approved therapies demonstrated superiority with regard to overall response rate and progression free survival over traditional systemic therapies. Other promising treatments such as lacutamab and PD-1/L-1 inhibitors are in the pipeline, and more therapeutic agents are currently investigated in clinical trials.

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How I treat mycosis fungoides and Sézary syndrome

Blood ◽

10.1182/blood-2015-12-611830 ◽

2016 ◽

Vol 127 (25) ◽

pp. 3142-3153 ◽

Cited By ~ 53

Author(s):

Sean Whittaker ◽

Richard Hoppe ◽

H. Miles Prince

Keyword(s):

Mycosis Fungoides ◽

Histone Deacetylase Inhibitors ◽

Early Stage ◽

Prognostic Index ◽

Interferon Α ◽

Sézary Syndrome ◽

Sezary Syndrome ◽

Advanced Stage ◽

Early Stage Disease ◽

Stage Disease

AbstractMycosis 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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How I treat mycosis fungoides and Sézary syndrome

Blood ◽

10.1182/blood-2009-07-202895 ◽

2009 ◽

Vol 114 (20) ◽

pp. 4337-4353 ◽

Cited By ~ 102

Author(s):

H. Miles Prince ◽

Sean Whittaker ◽

Richard T. Hoppe

Keyword(s):

Histone Deacetylase ◽

Mycosis Fungoides ◽

Histone Deacetylase Inhibitors ◽

Early Stage ◽

Ultraviolet B ◽

Interferon Α ◽

Sézary Syndrome ◽

Sezary Syndrome ◽

Early Stage Disease ◽

Stage Disease

AbstractThe 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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Systemic Treatment Options for Advanced-Stage Mycosis Fungoides and Sézary Syndrome

Current Oncology Reports ◽

10.1007/s11912-018-0678-x ◽

2018 ◽

Vol 20 (4) ◽

Cited By ~ 6

Author(s):

Louise Photiou ◽

Carrie van der Weyden ◽

Christopher McCormack ◽

H. Miles Prince

Keyword(s):

Mycosis Fungoides ◽

Systemic Treatment ◽

Treatment Options ◽

Sézary Syndrome ◽

Sezary Syndrome ◽

Advanced Stage

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Integrating novel systemic therapies for the treatment of mycosis fungoides and Sézary syndrome

Best Practice & Research Clinical Haematology ◽

10.1016/j.beha.2018.07.007 ◽

2018 ◽

Vol 31 (3) ◽

pp. 322-335 ◽

Cited By ~ 4

Author(s):

H. Miles Prince ◽

Christiane Querfeld

Keyword(s):

Mycosis Fungoides ◽

Sézary Syndrome ◽

Sezary Syndrome ◽

Systemic Therapies

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New and established treatment options for mycosis fungoides and Sézary syndrome - an update

JDDG Journal der Deutschen Dermatologischen Gesellschaft ◽

10.1111/ddg.12376 ◽

2014 ◽

Vol 12 (7) ◽

pp. 561-569 ◽

Cited By ~ 2

Author(s):

Susanne Dugas-Breit ◽

Hans-Joachim Schulze ◽

Christian Hallermann

Keyword(s):

Mycosis Fungoides ◽

Treatment Options ◽

Sézary Syndrome ◽

Sezary Syndrome ◽

Established Treatment

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Mycosis fungoides and the Sézary syndrome: a review of pathogenesis, diagnosis, and therapy.

Journal of Clinical Oncology ◽

10.1200/jco.1991.9.7.1298 ◽

1991 ◽

Vol 9 (7) ◽

pp. 1298-1313 ◽

Cited By ~ 95

Author(s):

T M Kuzel ◽

H H Roenigk ◽

S T Rosen

Keyword(s):

Mycosis Fungoides ◽

Treatment Options ◽

Interleukin 2 ◽

Cell Phenotype ◽

Sézary Syndrome ◽

Sezary Syndrome ◽

Phase Ii Trials ◽

Biologic Response ◽

Potential Benefits ◽

Hodgkin's Lymphomas

Mycosis fungoides (MF) and the Sézary syndrome (SS) are non-Hodgkin's lymphomas with a T-cell phenotype, which have cutaneous involvement as their predominant feature. These disorders are becoming more common, and the patients are frequently being referred to medical oncologists for assistance in management. The development of advanced laboratory techniques, such as molecular genetics and cell-surface phenotyping, has greatly enhanced our understanding of their pathogenesis and may lead to identification of responsible etiologic factors. A myriad of treatment options have been investigated including topical approaches, systemic chemotherapy, and external radiation. Currently, extensive trials are underway examining the potential benefits of agents such as the interferons, interleukin-2, monoclonal antibodies, the retinoids, 2-chlorodeoxyadenosine, and other novel biologic response modifiers or chemotherapeutics. Although all these therapies have benefit in phase II trials, few randomized comparative trials have been performed to identify optimal therapies. Performance of such trials should now become a priority.

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