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Mycosis Fungoides and the Sézary Syndrome Treatment (PDQ®)

Health Professional Version

.

Published online: December 23, 2015.

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of mycosis fungoides and the Sézary Syndrome. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

General Information About Mycosis Fungoides and the Sézary Syndrome

Clinical Presentation

Mycosis fungoides and the Sézary syndrome (MF/SS) are neoplasias of malignant T lymphocytes that usually possess the helper/inducer cell surface phenotype. These kinds of neoplasms initially present as skin involvement and, as such, have been classified as cutaneous T-cell lymphomas.[1] These types of lymphomas are included in the Revised European-American Lymphoma classification as low-grade T-cell lymphomas, which should be distinguished from other T-cell lymphomas that involve the skin, such as anaplastic large cell lymphoma (CD30 positive), peripheral T-cell lymphoma (CD30 negative, with no epidermal involvement), adult T-cell leukemia/lymphoma (usually with systemic involvement), or subcutaneous panniculitic T-cell lymphoma.[2,3] These histologic types of T-cell lymphomas are discussed in another PDQ summary. (Refer to the PDQ summary on Adult Non-Hodgkin Lymphoma Treatment for more information.) In addition, a number of benign or very indolent conditions can be confused with mycosis fungoides. Consultation with a pathologist who has expertise in distinguishing these conditions is important.[4]

Prognosis and Survival

The prognosis of patients with MF/SS is based on the extent of disease at presentation (stage).[5] The presence of lymphadenopathy and involvement of peripheral blood and viscera increase in likelihood with worsening cutaneous involvement and define poor prognostic groups.[5-7] The median survival following diagnosis varies according to stage. Patients with stage IA disease have a median survival of 20 or more years. Most deaths for this group are not caused by, nor are they related to, MF.[8] In contrast, more than 50% of patients with stage III through stage IV disease die of MF, with a median survival of less than 5 years.[7,9,10] A report on 1,798 patients from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program (SEER) database found an increase in second malignancies (standardized incidence ratio of 1.32; 95% confidence interval, 1.15–1.52), especially for Hodgkin lymphoma, non-Hodgkin lymphoma, and myeloma.[11]

Typically, the natural history of MF is indolent.[12] Symptoms of the disease may present for long periods, an average of 2 to 10 years, as waxing and waning cutaneous eruptions before biopsy confirmation. MF/SS is treatable with available topical and/or systemic therapies. Curative modalities, however, have thus far proven elusive, with the possible exception of patients with minimal disease confined to the skin.

Cutaneous disease typically progresses from an eczematous patch/plaque stage covering less than 10% of the body surface (T1) to plaque stage covering 10% or more of the body surface (T2), and finally to tumors (T3) that frequently undergo necrotic ulceration.[4,13] A retrospective study with a median follow-up of 14.5 years showed that 20% of the 1,422 patients progressed from stage I or II disease to stage III or IV disease.[14] SS presents with generalized erythroderma (T4) and peripheral blood involvement. However, there is some disagreement about whether the MF and SS are actually variants of the same disease.[15] The same retrospective study with a median follow-up of 14.5 years found that only 3% of 1,422 patients progressed from MF to SS.[14] There is consensus that patients with SS have a poor prognosis (median survival of 4 years).[16] Cytologic transformation from a low-grade lymphoma to a high-grade lymphoma (large-cell transformation) occurs rarely (<5%) during the course of these diseases and is associated with a poor prognosis.[17-19] A retrospective analysis of 100 cases with large-cell transformation found reduced disease-specific survival with extracutaneous transformation, increased extent of skin lesions, and CD30 negativity.[20] A common cause of death during the tumor phase is sepsis from Pseudomonas aeruginosa or Staphylococcus aureus caused by chronic skin infection with staph species and subsequent systemic infections.[13]

References

  1. Girardi M, Heald PW, Wilson LD: The pathogenesis of mycosis fungoides. N Engl J Med 350 (19): 1978-88, 2004. [PubMed: 15128898]
  2. Willemze R, Kerl H, Sterry W, et al.: EORTC classification for primary cutaneous lymphomas: a proposal from the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer. Blood 90 (1): 354-71, 1997. [PubMed: 9207472]
  3. Harris NL, Jaffe ES, Stein H, et al.: A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 84 (5): 1361-92, 1994. [PubMed: 8068936]
  4. Siegel RS, Pandolfino T, Guitart J, et al.: Primary cutaneous T-cell lymphoma: review and current concepts. J Clin Oncol 18 (15): 2908-25, 2000. [PubMed: 10920140]
  5. Agar NS, Wedgeworth E, Crichton S, et al.: Survival outcomes and prognostic factors in mycosis fungoides/Sézary syndrome: validation of the revised International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer staging proposal. J Clin Oncol 28 (31): 4730-9, 2010. [PubMed: 20855822]
  6. Talpur R, Singh L, Daulat S, et al.: Long-term outcomes of 1,263 patients with mycosis fungoides and Sézary syndrome from 1982 to 2009. Clin Cancer Res 18 (18): 5051-60, 2012. [PMC free article: PMC3857608] [PubMed: 22850569]
  7. Kim YH, Liu HL, Mraz-Gernhard S, et al.: Long-term outcome of 525 patients with mycosis fungoides and Sezary syndrome: clinical prognostic factors and risk for disease progression. Arch Dermatol 139 (7): 857-66, 2003. [PubMed: 12873880]
  8. Kim YH, Jensen RA, Watanabe GL, et al.: Clinical stage IA (limited patch and plaque) mycosis fungoides. A long-term outcome analysis. Arch Dermatol 132 (11): 1309-13, 1996. [PubMed: 8915308]
  9. Zackheim HS, Amin S, Kashani-Sabet M, et al.: Prognosis in cutaneous T-cell lymphoma by skin stage: long-term survival in 489 patients. J Am Acad Dermatol 40 (3): 418-25, 1999. [PubMed: 10071312]
  10. de Coninck EC, Kim YH, Varghese A, et al.: Clinical characteristics and outcome of patients with extracutaneous mycosis fungoides. J Clin Oncol 19 (3): 779-84, 2001. [PubMed: 11157031]
  11. Huang KP, Weinstock MA, Clarke CA, et al.: Second lymphomas and other malignant neoplasms in patients with mycosis fungoides and Sezary syndrome: evidence from population-based and clinical cohorts. Arch Dermatol 143 (1): 45-50, 2007. [PubMed: 17224541]
  12. Diamandidou E, Cohen PR, Kurzrock R: Mycosis fungoides and Sezary syndrome. Blood 88 (7): 2385-409, 1996. [PubMed: 8839829]
  13. Lorincz AL: Cutaneous T-cell lymphoma (mycosis fungoides) Lancet 347 (9005): 871-6, 1996. [PubMed: 8622396]
  14. Quaglino P, Pimpinelli N, Berti E, et al.: Time course, clinical pathways, and long-term hazards risk trends of disease progression in patients with classic mycosis fungoides: a multicenter, retrospective follow-up study from the Italian Group of Cutaneous Lymphomas. Cancer 118 (23): 5830-9, 2012. [PubMed: 22674564]
  15. Olsen EA, Rook AH, Zic J, et al.: Sézary syndrome: immunopathogenesis, literature review of therapeutic options, and recommendations for therapy by the United States Cutaneous Lymphoma Consortium (USCLC). J Am Acad Dermatol 64 (2): 352-404, 2011. [PubMed: 21145619]
  16. Kubica AW, Davis MD, Weaver AL, et al.: Sézary syndrome: a study of 176 patients at Mayo Clinic. J Am Acad Dermatol 67 (6): 1189-99, 2012. [PubMed: 22640839]
  17. Kim YH, Bishop K, Varghese A, et al.: Prognostic factors in erythrodermic mycosis fungoides and the Sézary syndrome. Arch Dermatol 131 (9): 1003-8, 1995. [PubMed: 7661601]
  18. Arulogun SO, Prince HM, Ng J, et al.: Long-term outcomes of patients with advanced-stage cutaneous T-cell lymphoma and large cell transformation. Blood 112 (8): 3082-7, 2008. [PubMed: 18647960]
  19. Kadin ME, Hughey LC, Wood GS: Large-cell transformation of mycosis fungoides-differential diagnosis with implications for clinical management: a consensus statement of the US Cutaneous Lymphoma Consortium. J Am Acad Dermatol 70 (2): 374-6, 2014. [PubMed: 24438952]
  20. Benner MF, Jansen PM, Vermeer MH, et al.: Prognostic factors in transformed mycosis fungoides: a retrospective analysis of 100 cases. Blood 119 (7): 1643-9, 2012. [PubMed: 22160616]

Cellular Classification of Mycosis Fungoides and the Sézary Syndrome

The histologic diagnosis of mycosis fungoides and the Sézary syndrome (MF/SS) is usually difficult to determine in the initial stages of the disease and may require the review of multiple biopsies by an experienced pathologist.

A definitive diagnosis from a skin biopsy requires the presence of MF/SS cells (convoluted lymphocytes), a band-like upper dermal infiltrate, and epidermal infiltrations with Pautrier abscesses (collections of neoplastic lymphocytes). A definitive diagnosis of SS may be made from a peripheral blood evaluation when skin biopsies are consistent with the diagnosis. Supportive evidence for circulating Sézary cells is provided by T-cell receptor gene analysis, identification of the atypical lymphocytes with hyper-convoluted or cerebriform nuclei, and flow cytometry with the characteristic deletion of cell surface markers such as CD7 and CD26. However, none of these is individually pathognomonic for lymphoma.[1,2]

References

  1. Olsen EA, Rook AH, Zic J, et al.: Sézary syndrome: immunopathogenesis, literature review of therapeutic options, and recommendations for therapy by the United States Cutaneous Lymphoma Consortium (USCLC). J Am Acad Dermatol 64 (2): 352-404, 2011. [PubMed: 21145619]
  2. Fraser-Andrews EA, Russell-Jones R, Woolford AJ, et al.: Diagnostic and prognostic importance of T-cell receptor gene analysis in patients with Sézary syndrome. Cancer 92 (7): 1745-52, 2001. [PubMed: 11745245]

Stage Information for Mycosis Fungoides and the Sézary Syndrome

The stages that follow are defined by TNM classification. Peripheral blood involvement with mycosis fungoides or Sézary syndrome (MF/SS) cells is correlated with more advanced skin stage, lymph node and visceral involvement, and shortened survival.

MF/SS have a formal staging system proposed by the International Society for Cutaneous Lymphomas (ISCL) and the European Organization of Research and Treatment of Cancer (EORTC).[1,2]

Definitions of TNM

The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification to define MF.[3]

Table 1. ISCL/EORTC Revision to the Classification of Mycosis Fungoides and the Sézary Syndromea

Skin
T1Limited patches,b papules, and/or plaquesc covering <10% of the skin surface. May further stratify into T1a (patch only) vs. T1b (plaque ± patch).
T2Patches, papules, or plaques covering ≥10% of the skin surface. May further stratify into T2a (patch only) vs. T2b (plaque ± patch).
T3≥1 tumord (≥1 cm diameter).
T4Confluence of erythema covering ≥80% of body surface area.
Node
N0No clinically abnormal peripheral lymph nodes;e biopsy not required.
N1Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 1 or NCI LN0–2.
N1aClone negative.f
N1bClone positive.f
N2Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 2 or NCI LN3.
N2aClone negative.f
N2bClone positive.f
N3Clinically abnormal peripheral lymph nodes; histopathology Dutch grades 3–4 or NCI LN4; clone positive or negative.
NxClinically abnormal peripheral lymph nodes; no histologic confirmation.
Visceral
M0No visceral organ involvement.
M1Visceral involvement (must have pathology confirmation,g and organ involved should be specified).
Peripheral Blood Involvement
B0Absence of significant blood involvement: ≤5% of peripheral blood lymphocytes are atypical (Sézary) cells.h
B0aClone negative.f
B0bClone positive.f
B1Low blood-tumor burden: >5% of peripheral blood lymphocytes are atypical (Sézary) cells but does not meet the criteria of B2.
B1aClone negative.f
B1bClone positive.f
B2High blood-tumor burden: ≥1,000/μL Sézary cellsh with positive clone.f

EORTC = European Organization of Research and Treatment of Cancer; ISCL = International Society for Cutaneous Lymphomas; NCI = National Cancer Institute.

aReprinted with permission from AJCC: Primary cutaneous lymphomas. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, p 613-5.

bFor skin, patch indicates any size skin lesion without significant elevation or induration. Presence/absence of hypo- or hyperpigmentation, scale, crusting, and/or poikiloderma should be noted.

cFor skin, plaque indicates any size skin lesion that is elevated or indurated. Presence or absence of scale, crusting, and/or poikiloderma should be noted. Histologic features such as folliculotropism or large-cell transformation (>25% large cells), CD30+ or CD30-, and clinical features, such as ulceration, are important to document.

dFor skin, tumor indicates at least 1 cm diameter solid or nodular lesion with evidence of depth and/or vertical growth. Note total number of lesions, total volume of lesions, largest size lesion, and region of body involved. Also, note if histologic evidence of large cell transformation has occurred. Phenotyping for CD30 is encouraged.

eFor node, abnormal peripheral lymph node(s) indicates any palpable peripheral node that on physical examination is firm, irregular, clustered, fixed, or ≥1.5 cm in diameter. Node groups examined on physical examination include: cervical, supraclavicular, epitrochlear, axillary, and inguinal. Central nodes, which are not generally amenable to pathologic assessment, are not currently considered in the nodal classification unless used to establish N3 histopathologically.

fA T-cell clone is defined by polymerase chain reaction or Southern blot analysis of the T-cell receptor (TCR) gene.

gFor viscera, spleen and liver may be diagnosed by imaging criteria.

hFor blood, Sézary cells are defined as lymphocytes with hyper-convoluted cerebriform nuclei. If Sézary cells are not able to be used to determine tumor burden for B2, then one of the following modified ISCL criteria along with a positive clonal rearrangement of the TCR may be used instead: (1) expanded CD4+ or CD3+ cells with CD4/CD8 ratio of ≥10; and (2) expanded CD4+ cells with abnormal immunophenotype, including loss of CD7 or CD26.

Table 2. Anatomic Stage/Prognostic Groupsa,b

ISCL/EORTC Revision to the Staging of Mycosis Fungoides and the Sézary Syndrome
StageTNMPeripheral Blood Involvement
IA1000, 1
IB2000, 1
IIA1, 21, 200, 1
IIB30–200, 1
III40–200, 1
IIIA40–200
IIIB40–201
IVA11–40–202
IVA21–4300–2
IVB1–40–310–2

EORTC = European Organization of Research and Treatment of Cancer; ISCL = International Society for Cutaneous Lymphomas.

aReprinted with permission from AJCC: Primary cutaneous lymphomas. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, p 613-5.

bAdapted from Olsen et al.[1]

Clinical trials have assessed the extent of skin involvement using detailed scoring systems such as the modified Severity-Weighted Assessment Tool (mSWAT).[4]

References

  1. Olsen E, Vonderheid E, Pimpinelli N, et al.: Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC). Blood 110 (6): 1713-22, 2007. [PubMed: 17540844]
  2. Agar NS, Wedgeworth E, Crichton S, et al.: Survival outcomes and prognostic factors in mycosis fungoides/Sézary syndrome: validation of the revised International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer staging proposal. J Clin Oncol 28 (31): 4730-9, 2010. [PubMed: 20855822]
  3. Primary cutaneous lymphomas. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 614-5.
  4. Olsen EA, Whittaker S, Kim YH, et al.: Clinical end points and response criteria in mycosis fungoides and Sézary syndrome: a consensus statement of the International Society for Cutaneous Lymphomas, the United States Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer. J Clin Oncol 29 (18): 2598-607, 2011. [PMC free article: PMC3422534] [PubMed: 21576639]

Treatment Option Overview

Treatment options for patients with mycosis fungoides and the Sézary syndrome (MF/SS) include the following:[1-3]

  1. Topical corticosteroids.
  2. Topical chemotherapy with mechlorethamine (nitrogen mustard) or carmustine (BCNU).
  3. Psoralen and ultraviolet A radiation (PUVA).
  4. Ultraviolet B radiation (UVB).
  5. Total-skin electron-beam radiation (TSEB).
  6. Radiation of symptomatic skin lesions.
  7. Interferon alpha or interferon gamma alone or in combination with topical therapy.
  8. Single-agent and multiagent chemotherapy.
  9. Bexarotene (topical gel or oral); retinoids.
  10. Denileukin diftitox (recombinant fusion protein of diphtheria toxin fragments and interleukin-2 sequences).
  11. Vorinostat or romidepsin or other histone deacetylase inhibitors.
  12. Pralatrexate (folate analog).[4]
  13. Alemtuzumab (a humanized monoclonal antibody targeting the CD52 antigen).
  14. Combined-modality treatment.

These types of treatments produce remissions, but long-term remissions are uncommon. Treatment, therefore, is considered palliative for most patients, although major symptomatic improvement is regularly achieved. Survival in excess of 8 years, however, is common for patients with early stages of disease. All patients with MF/SS are candidates for clinical trials evaluating new approaches to treatment.

Current areas of interest in clinical trials for MF confined to the skin include combined-modality therapies containing both topical and systemic agents such as TSEB combined with chemotherapy, topical mechlorethamine or PUVA combined with interferon, or wide-field radiation techniques with PUVA. Reports are available of activity for extracorporeal photochemotherapy using psoralen; interferon gamma or interferon alpha; pentostatin; retinoids; fludarabine; acyclovir; 2-chlorodeoxyadenosine; serotherapy with unlabeled, toxin-labeled, or radiolabeled monoclonal antibodies; cell surface receptor ligand-toxin fusion protein; and, methotrexate.[3,5-14] Antigen-specific vaccination using dendritic cells [15] and UVB are also under clinical evaluation.

References

  1. Prince HM, Whittaker S, Hoppe RT: How I treat mycosis fungoides and Sézary syndrome. Blood 114 (20): 4337-53, 2009. [PubMed: 19696197]
  2. Trautinger F, Knobler R, Willemze R, et al.: EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome. Eur J Cancer 42 (8): 1014-30, 2006. [PubMed: 16574401]
  3. Olsen EA, Rook AH, Zic J, et al.: Sézary syndrome: immunopathogenesis, literature review of therapeutic options, and recommendations for therapy by the United States Cutaneous Lymphoma Consortium (USCLC). J Am Acad Dermatol 64 (2): 352-404, 2011. [PubMed: 21145619]
  4. Horwitz SM, Kim YH, Foss F, et al.: Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood 119 (18): 4115-22, 2012. [PubMed: 22394596]
  5. Kaplan EH, Rosen ST, Norris DB, et al.: Phase II study of recombinant human interferon gamma for treatment of cutaneous T-cell lymphoma. J Natl Cancer Inst 82 (3): 208-12, 1990. [PubMed: 2104937]
  6. Heald P, Rook A, Perez M, et al.: Treatment of erythrodermic cutaneous T-cell lymphoma with extracorporeal photochemotherapy. J Am Acad Dermatol 27 (3): 427-33, 1992. [PubMed: 1401279]
  7. Rosen ST, Zimmer AM, Goldman-Leikin R, et al.: Radioimmunodetection and radioimmunotherapy of cutaneous T cell lymphomas using an 131I-labeled monoclonal antibody: an Illinois Cancer Council Study. J Clin Oncol 5 (4): 562-73, 1987. [PubMed: 3549989]
  8. Foss FM, Ihde DC, Breneman DL, et al.: Phase II study of pentostatin and intermittent high-dose recombinant interferon alfa-2a in advanced mycosis fungoides/Sézary syndrome. J Clin Oncol 10 (12): 1907-13, 1992. [PubMed: 1453206]
  9. Saven A, Carrera CJ, Carson DA, et al.: 2-Chlorodeoxyadenosine: an active agent in the treatment of cutaneous T-cell lymphoma. Blood 80 (3): 587-92, 1992. [PubMed: 1353380]
  10. Kuzel TM, Roenigk HH Jr, Samuelson E, et al.: Effectiveness of interferon alfa-2a combined with phototherapy for mycosis fungoides and the Sézary syndrome. J Clin Oncol 13 (1): 257-63, 1995. [PubMed: 7799028]
  11. Olsen E, Duvic M, Frankel A, et al.: Pivotal phase III trial of two dose levels of denileukin diftitox for the treatment of cutaneous T-cell lymphoma. J Clin Oncol 19 (2): 376-88, 2001. [PubMed: 11208829]
  12. Siegel RS, Pandolfino T, Guitart J, et al.: Primary cutaneous T-cell lymphoma: review and current concepts. J Clin Oncol 18 (15): 2908-25, 2000. [PubMed: 10920140]
  13. Duvic M, Hymes K, Heald P, et al.: Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: multinational phase II-III trial results. J Clin Oncol 19 (9): 2456-71, 2001. [PubMed: 11331325]
  14. Zackheim HS, Kashani-Sabet M, McMillan A: Low-dose methotrexate to treat mycosis fungoides: a retrospective study in 69 patients. J Am Acad Dermatol 49 (5): 873-8, 2003. [PubMed: 14576667]
  15. Maier T, Tun-Kyi A, Tassis A, et al.: Vaccination of patients with cutaneous T-cell lymphoma using intranodal injection of autologous tumor-lysate-pulsed dendritic cells. Blood 102 (7): 2338-44, 2003. [PubMed: 12714511]

Stage I Mycosis Fungoides

Because several forms of treatment can produce complete resolution of skin lesions in this stage, the choice of therapy is dependent on local expertise and the facilities available. With therapy, the survival of patients with stage IA disease can be expected to be the same as age and gender-matched controls.[1,2]

Treatment options:[3]

  1. Psoralen and ultraviolet A radiation (PUVA). Therapeutic trials with PUVA have shown a 62% to 90% complete remission rate with, early cutaneous stages achieving the best responses. Continued maintenance therapy with PUVA at more protracted intervals is generally required to prolong remission duration.[4-6] PUVA combined with interferon alpha-2a is associated with a high response rate.[7]
  2. Total-skin electron-beam radiation. Electron radiation of appropriate energies will penetrate only to the dermis, and thus the skin alone can be treated without systemic effects. This therapy requires considerable technical expertise to deliver, can result in short- and long-term cutaneous toxic effects, and is not widely available. Based on the long-term survival of these early-stage patients, electron-beam radiation therapy is sometimes used with curative intent.[8-11] Long-term disease-free survival (DFS) can be achieved in patients with unilesional mycosis fungoides treated with local radiation therapy.[12]
  3. Ultraviolet B radiation.[13]
  4. Symptomatic management with topical corticosteroids.
  5. Topical mechlorethamine (nitrogen mustard). Topical application of mechlorethamine has produced regression of cutaneous lesions, with particular efficacy in early stages of disease. The overall complete remission rate is related to skin stage; 50% to 80% of TNM classification T1, and 25% to 75% of T2 patients have complete responses. Treatments are usually continued for 2 to 3 years. Continuous 5-year DFS may be possible in as many as 33% of T1 patients.[8,14,15]
  6. Local electron-beam radiation or orthovoltage radiation therapy may be used to palliate areas of bulky or symptomatic skin disease.[16]
  7. Interferon alpha alone or in combination with topical therapy, as evidenced in the ECOG-1495 trial.[17,18] A retrospective review of 198 patients with mycosis fungoides and the Sézary syndrome compared time to next treatment (TTNT) between interferon alpha and conventional chemotherapy. Interferon alpha provided a longer TTNT of 8.7 months (95% confidence interval [CI], 6.0–18.0) than did chemotherapy, with a TTNT of 3.9 months (95% CI, 3.2–5.1) and P < .00001.[19][Level of evidence: 3iiiDiv]
  8. Bexarotene, an oral or topical retinoid (NCT00255801).[20,21]
  9. Oral methotrexate (NCT00425555).[22]
  10. Pegylated liposomal doxorubicin.[23]
  11. Vorinostat or romidepsin or other histone deacetylase inhibitors (HDACi).[24-26] A retrospective review of 198 patients with mycosis fungoides and the Sézary syndrome compared TTNT between HDACi and conventional chemotherapy. HDACi provided a longer TTNT of 4.5 months (95% CI, 4.0–6.1) than did chemotherapy with a TTNT of 3.9 months (95% CI, 3.2–5.1) and P = .01.[19][Level of evidence: 3iiiDiv]
  12. Pralatrexate (folate analog).[27,28]
  13. Lenalidomide.[29]

Current Clinical Trials

Check the list of NCI-supported cancer clinical trials that are now accepting patients with stage I mycosis fungoides/Sezary syndrome. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI website.

References

  1. Kim YH, Jensen RA, Watanabe GL, et al.: Clinical stage IA (limited patch and plaque) mycosis fungoides. A long-term outcome analysis. Arch Dermatol 132 (11): 1309-13, 1996. [PubMed: 8915308]
  2. Zackheim HS, Amin S, Kashani-Sabet M, et al.: Prognosis in cutaneous T-cell lymphoma by skin stage: long-term survival in 489 patients. J Am Acad Dermatol 40 (3): 418-25, 1999. [PubMed: 10071312]
  3. Trautinger F, Knobler R, Willemze R, et al.: EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome. Eur J Cancer 42 (8): 1014-30, 2006. [PubMed: 16574401]
  4. Herrmann JJ, Roenigk HH Jr, Hurria A, et al.: Treatment of mycosis fungoides with photochemotherapy (PUVA): long-term follow-up. J Am Acad Dermatol 33 (2 Pt 1): 234-42, 1995. [PubMed: 7622650]
  5. Ramsay DL, Lish KM, Yalowitz CB, et al.: Ultraviolet-B phototherapy for early-stage cutaneous T-cell lymphoma. Arch Dermatol 128 (7): 931-3, 1992. [PubMed: 1626959]
  6. Querfeld C, Rosen ST, Kuzel TM, et al.: Long-term follow-up of patients with early-stage cutaneous T-cell lymphoma who achieved complete remission with psoralen plus UV-A monotherapy. Arch Dermatol 141 (3): 305-11, 2005. [PubMed: 15781671]
  7. Kuzel TM, Roenigk HH Jr, Samuelson E, et al.: Effectiveness of interferon alfa-2a combined with phototherapy for mycosis fungoides and the Sézary syndrome. J Clin Oncol 13 (1): 257-63, 1995. [PubMed: 7799028]
  8. Chinn DM, Chow S, Kim YH, et al.: Total skin electron beam therapy with or without adjuvant topical nitrogen mustard or nitrogen mustard alone as initial treatment of T2 and T3 mycosis fungoides. Int J Radiat Oncol Biol Phys 43 (5): 951-8, 1999. [PubMed: 10192339]
  9. Quirós PA, Jones GW, Kacinski BM, et al.: Total skin electron beam therapy followed by adjuvant psoralen/ultraviolet-A light in the management of patients with T1 and T2 cutaneous T-cell lymphoma (mycosis fungoides). Int J Radiat Oncol Biol Phys 38 (5): 1027-35, 1997. [PubMed: 9276369]
  10. Ysebaert L, Truc G, Dalac S, et al.: Ultimate results of radiation therapy for T1-T2 mycosis fungoides (including reirradiation). Int J Radiat Oncol Biol Phys 58 (4): 1128-34, 2004. [PubMed: 15001254]
  11. Navi D, Riaz N, Levin YS, et al.: The Stanford University experience with conventional-dose, total skin electron-beam therapy in the treatment of generalized patch or plaque (T2) and tumor (T3) mycosis fungoides. Arch Dermatol 147 (5): 561-7, 2011. [PubMed: 21576575]
  12. Micaily B, Miyamoto C, Kantor G, et al.: Radiotherapy for unilesional mycosis fungoides. Int J Radiat Oncol Biol Phys 42 (2): 361-4, 1998. [PubMed: 9788416]
  13. Elcin G, Duman N, Karahan S, et al.: Long-term follow-up of early mycosis fungoides patients treated with narrowband ultraviolet B phototherapy. J Dermatolog Treat 25 (3): 268-73, 2014. [PubMed: 23030414]
  14. Lessin SR, Duvic M, Guitart J, et al.: Topical chemotherapy in cutaneous T-cell lymphoma: positive results of a randomized, controlled, multicenter trial testing the efficacy and safety of a novel mechlorethamine, 0.02%, gel in mycosis fungoides. JAMA Dermatol 149 (1): 25-32, 2013. [PMC free article: PMC3662469] [PubMed: 23069814]
  15. de Quatrebarbes J, Estève E, Bagot M, et al.: Treatment of early-stage mycosis fungoides with twice-weekly applications of mechlorethamine and topical corticosteroids: a prospective study. Arch Dermatol 141 (9): 1117-20, 2005. [PubMed: 16172308]
  16. Thomas TO, Agrawal P, Guitart J, et al.: Outcome of patients treated with a single-fraction dose of palliative radiation for cutaneous T-cell lymphoma. Int J Radiat Oncol Biol Phys 85 (3): 747-53, 2013. [PubMed: 22818412]
  17. Foss FM, Ihde DC, Breneman DL, et al.: Phase II study of pentostatin and intermittent high-dose recombinant interferon alfa-2a in advanced mycosis fungoides/Sézary syndrome. J Clin Oncol 10 (12): 1907-13, 1992. [PubMed: 1453206]
  18. Olsen EA, Bunn PA: Interferon in the treatment of cutaneous T-cell lymphoma. Hematol Oncol Clin North Am 9 (5): 1089-107, 1995. [PubMed: 8522486]
  19. Hughes CF, Khot A, McCormack C, et al.: Lack of durable disease control with chemotherapy for mycosis fungoides and Sézary syndrome: a comparative study of systemic therapy. Blood 125 (1): 71-81, 2015. [PubMed: 25336628]
  20. Duvic M, Hymes K, Heald P, et al.: Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: multinational phase II-III trial results. J Clin Oncol 19 (9): 2456-71, 2001. [PubMed: 11331325]
  21. Heald P, Mehlmauer M, Martin AG, et al.: Topical bexarotene therapy for patients with refractory or persistent early-stage cutaneous T-cell lymphoma: results of the phase III clinical trial. J Am Acad Dermatol 49 (5): 801-15, 2003. [PubMed: 14576658]
  22. Zackheim HS, Kashani-Sabet M, McMillan A: Low-dose methotrexate to treat mycosis fungoides: a retrospective study in 69 patients. J Am Acad Dermatol 49 (5): 873-8, 2003. [PubMed: 14576667]
  23. Wollina U, Dummer R, Brockmeyer NH, et al.: Multicenter study of pegylated liposomal doxorubicin in patients with cutaneous T-cell lymphoma. Cancer 98 (5): 993-1001, 2003. [PubMed: 12942567]
  24. Duvic M, Dummer R, Becker JC, et al.: Panobinostat activity in both bexarotene-exposed and -naïve patients with refractory cutaneous T-cell lymphoma: results of a phase II trial. Eur J Cancer 49 (2): 386-94, 2013. [PubMed: 22981498]
  25. Olsen EA, Kim YH, Kuzel TM, et al.: Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma. J Clin Oncol 25 (21): 3109-15, 2007. [PubMed: 17577020]
  26. Piekarz RL, Frye R, Turner M, et al.: Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma. J Clin Oncol 27 (32): 5410-7, 2009. [PMC free article: PMC2773225] [PubMed: 19826128]
  27. Horwitz SM, Kim YH, Foss F, et al.: Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood 119 (18): 4115-22, 2012. [PubMed: 22394596]
  28. Talpur R, Thompson A, Gangar P, et al.: Pralatrexate alone or in combination with bexarotene: long-term tolerability in relapsed/refractory mycosis fungoides. Clin Lymphoma Myeloma Leuk 14 (4): 297-304, 2014. [PubMed: 24589156]
  29. Querfeld C, Rosen ST, Guitart J, et al.: Results of an open-label multicenter phase 2 trial of lenalidomide monotherapy in refractory mycosis fungoides and Sézary syndrome. Blood 123 (8): 1159-66, 2014. [PubMed: 24335103]

Stage II Mycosis Fungoides

No curative therapy exists for patients with stage II disease. Therefore, the choice of initial palliative therapy is dependent on the patient’s symptoms and the local expertise with each modality.

A randomized study of 103 patients compared combined total-skin electron-beam radiation (TSEB) plus combination chemotherapy with conservation therapy consisting of sequential topical therapies.[1] In the latter group, combination chemotherapy was reserved for symptomatic extracutaneous disease or for disease refractory to topical therapies. Patients with any stage were eligible. Although the complete response rate was higher with combined therapy, toxic effects were considerably greater, and no difference was seen in disease-free or overall survival between the two groups.[1][Level of evidence: 1iiA]

Treatment options:[2]

  1. Psoralen and ultraviolet A radiation (PUVA). Therapeutic trials with PUVA have shown a 62% to 90% complete remission rate with early cutaneous stages achieving the best responses. Maintenance therapy with PUVA is generally required to prolong remission duration.[3,4] PUVA combined with interferon alpha-2a is associated with a high response rate.[5]
  2. TSEB. Electron radiation of appropriate energies will penetrate only to the dermis, and the skin alone can be treated without systemic effects. This therapy requires a radiation therapy facility with physics support, considerable technical expertise, and precise dosimetry. The therapy can provide excellent palliation, with complete response rates of as much as 80%.[6-9]
  3. Ultraviolet B radiation.[10]
  4. Symptomatic management with topical corticosteroids.
  5. Topical mechlorethamine (nitrogen mustard). Topical application of mechlorethamine has produced regression of cutaneous lesions with particular efficacy in early stages of the disease. The overall complete remission rate is related to skin stage; 25% to 75% of TNM classification T2, and as many as 50% of T3 patients have complete responses. Treatments are usually continued for 2 to 3 years.[6,11,12]
  6. Local electron-beam radiation or orthovoltage radiation therapy may also be used to palliate areas of bulky or symptomatic disease.[13]
  7. Interferon alpha alone or in combination with topical therapy, as evidenced in the ECOG-1495 trial.[14,15] A retrospective review of 198 patients with mycosis fungoides and the Sézary syndrome compared time to next treatment (TTNT) between interferon alpha and conventional chemotherapy. Interferon alpha provided a longer TTNT of 8.7 months (95% confidence interval [CI], 6.0–18.0) than did chemotherapy, with a TTNT of 3.9 months (95% CI, 3.2–5.1) and P < .00001.[16][Level of evidence: 3iiiDiv]
  8. Bexarotene, an oral or topical retinoid.[17,18]
  9. Oral methotrexate (NCT00425555).[19]
  10. Pegylated liposomal doxorubicin.[20-22]
  11. Vorinostat or romidepsin or other histone deacetylase inhibitors (HDACi).[23-25] A retrospective review of 198 patients with mycosis fungoides and the Sézary syndrome compared TTNT between HDACi and conventional chemotherapy. HDACi provided a longer TTNT of 4.5 months (95% CI, 4.0–6.1) than did chemotherapy with, a TTNT of 3.9 months (95% CI, 3.2–5.1) and P = .01.[16][Level of evidence: 3iiiDiv]
  12. Pralatrexate (folate analog).[26,27]
  13. Lenalidomide.[28]

Current Clinical Trials

Check the list of NCI-supported cancer clinical trials that are now accepting patients with stage II mycosis fungoides/Sezary syndrome. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI website.

References

  1. Kaye FJ, Bunn PA Jr, Steinberg SM, et al.: A randomized trial comparing combination electron-beam radiation and chemotherapy with topical therapy in the initial treatment of mycosis fungoides. N Engl J Med 321 (26): 1784-90, 1989. [PubMed: 2594037]
  2. Trautinger F, Knobler R, Willemze R, et al.: EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome. Eur J Cancer 42 (8): 1014-30, 2006. [PubMed: 16574401]
  3. Herrmann JJ, Roenigk HH Jr, Hurria A, et al.: Treatment of mycosis fungoides with photochemotherapy (PUVA): long-term follow-up. J Am Acad Dermatol 33 (2 Pt 1): 234-42, 1995. [PubMed: 7622650]
  4. Querfeld C, Rosen ST, Kuzel TM, et al.: Long-term follow-up of patients with early-stage cutaneous T-cell lymphoma who achieved complete remission with psoralen plus UV-A monotherapy. Arch Dermatol 141 (3): 305-11, 2005. [PubMed: 15781671]
  5. Kuzel TM, Roenigk HH Jr, Samuelson E, et al.: Effectiveness of interferon alfa-2a combined with phototherapy for mycosis fungoides and the Sézary syndrome. J Clin Oncol 13 (1): 257-63, 1995. [PubMed: 7799028]
  6. Chinn DM, Chow S, Kim YH, et al.: Total skin electron beam therapy with or without adjuvant topical nitrogen mustard or nitrogen mustard alone as initial treatment of T2 and T3 mycosis fungoides. Int J Radiat Oncol Biol Phys 43 (5): 951-8, 1999. [PubMed: 10192339]
  7. Quirós PA, Jones GW, Kacinski BM, et al.: Total skin electron beam therapy followed by adjuvant psoralen/ultraviolet-A light in the management of patients with T1 and T2 cutaneous T-cell lymphoma (mycosis fungoides). Int J Radiat Oncol Biol Phys 38 (5): 1027-35, 1997. [PubMed: 9276369]
  8. Ysebaert L, Truc G, Dalac S, et al.: Ultimate results of radiation therapy for T1-T2 mycosis fungoides (including reirradiation). Int J Radiat Oncol Biol Phys 58 (4): 1128-34, 2004. [PubMed: 15001254]
  9. Navi D, Riaz N, Levin YS, et al.: The Stanford University experience with conventional-dose, total skin electron-beam therapy in the treatment of generalized patch or plaque (T2) and tumor (T3) mycosis fungoides. Arch Dermatol 147 (5): 561-7, 2011. [PubMed: 21576575]
  10. Elcin G, Duman N, Karahan S, et al.: Long-term follow-up of early mycosis fungoides patients treated with narrowband ultraviolet B phototherapy. J Dermatolog Treat 25 (3): 268-73, 2014. [PubMed: 23030414]
  11. Lessin SR, Duvic M, Guitart J, et al.: Topical chemotherapy in cutaneous T-cell lymphoma: positive results of a randomized, controlled, multicenter trial testing the efficacy and safety of a novel mechlorethamine, 0.02%, gel in mycosis fungoides. JAMA Dermatol 149 (1): 25-32, 2013. [PMC free article: PMC3662469] [PubMed: 23069814]
  12. de Quatrebarbes J, Estève E, Bagot M, et al.: Treatment of early-stage mycosis fungoides with twice-weekly applications of mechlorethamine and topical corticosteroids: a prospective study. Arch Dermatol 141 (9): 1117-20, 2005. [PubMed: 16172308]
  13. Thomas TO, Agrawal P, Guitart J, et al.: Outcome of patients treated with a single-fraction dose of palliative radiation for cutaneous T-cell lymphoma. Int J Radiat Oncol Biol Phys 85 (3): 747-53, 2013. [PubMed: 22818412]
  14. Foss FM, Ihde DC, Breneman DL, et al.: Phase II study of pentostatin and intermittent high-dose recombinant interferon alfa-2a in advanced mycosis fungoides/Sézary syndrome. J Clin Oncol 10 (12): 1907-13, 1992. [PubMed: 1453206]
  15. Olsen EA, Bunn PA: Interferon in the treatment of cutaneous T-cell lymphoma. Hematol Oncol Clin North Am 9 (5): 1089-107, 1995. [PubMed: 8522486]
  16. Hughes CF, Khot A, McCormack C, et al.: Lack of durable disease control with chemotherapy for mycosis fungoides and Sézary syndrome: a comparative study of systemic therapy. Blood 125 (1): 71-81, 2015. [PubMed: 25336628]
  17. Duvic M, Hymes K, Heald P, et al.: Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: multinational phase II-III trial results. J Clin Oncol 19 (9): 2456-71, 2001. [PubMed: 11331325]
  18. Heald P, Mehlmauer M, Martin AG, et al.: Topical bexarotene therapy for patients with refractory or persistent early-stage cutaneous T-cell lymphoma: results of the phase III clinical trial. J Am Acad Dermatol 49 (5): 801-15, 2003. [PubMed: 14576658]
  19. Zackheim HS, Kashani-Sabet M, McMillan A: Low-dose methotrexate to treat mycosis fungoides: a retrospective study in 69 patients. J Am Acad Dermatol 49 (5): 873-8, 2003. [PubMed: 14576667]
  20. Dummer R, Quaglino P, Becker JC, et al.: Prospective international multicenter phase II trial of intravenous pegylated liposomal doxorubicin monochemotherapy in patients with stage IIB, IVA, or IVB advanced mycosis fungoides: final results from EORTC 21012. J Clin Oncol 30 (33): 4091-7, 2012. [PubMed: 23045580]
  21. Wollina U, Dummer R, Brockmeyer NH, et al.: Multicenter study of pegylated liposomal doxorubicin in patients with cutaneous T-cell lymphoma. Cancer 98 (5): 993-1001, 2003. [PubMed: 12942567]
  22. Quereux G, Marques S, Nguyen JM, et al.: Prospective multicenter study of pegylated liposomal doxorubicin treatment in patients with advanced or refractory mycosis fungoides or Sézary syndrome. Arch Dermatol 144 (6): 727-33, 2008. [PubMed: 18559761]
  23. Duvic M, Dummer R, Becker JC, et al.: Panobinostat activity in both bexarotene-exposed and -naïve patients with refractory cutaneous T-cell lymphoma: results of a phase II trial. Eur J Cancer 49 (2): 386-94, 2013. [PubMed: 22981498]
  24. Olsen EA, Kim YH, Kuzel TM, et al.: Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma. J Clin Oncol 25 (21): 3109-15, 2007. [PubMed: 17577020]
  25. Piekarz RL, Frye R, Turner M, et al.: Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma. J Clin Oncol 27 (32): 5410-7, 2009. [PMC free article: PMC2773225] [PubMed: 19826128]
  26. Horwitz SM, Kim YH, Foss F, et al.: Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood 119 (18): 4115-22, 2012. [PubMed: 22394596]
  27. Talpur R, Thompson A, Gangar P, et al.: Pralatrexate alone or in combination with bexarotene: long-term tolerability in relapsed/refractory mycosis fungoides. Clin Lymphoma Myeloma Leuk 14 (4): 297-304, 2014. [PubMed: 24589156]
  28. Querfeld C, Rosen ST, Guitart J, et al.: Results of an open-label multicenter phase 2 trial of lenalidomide monotherapy in refractory mycosis fungoides and Sézary syndrome. Blood 123 (8): 1159-66, 2014. [PubMed: 24335103]

Stage III Mycosis Fungoides

No curative treatment exists for patients with stage III disease. Therefore, the initial choice of palliative therapy is dependent on the local expertise with each modality.

A randomized study of 103 patients compared combined total-skin electron-beam radiation (TSEB) plus combination chemotherapy with conservation therapy consisting of sequential topical therapies.[1] In the latter group, combination chemotherapy was reserved for symptomatic extracutaneous disease or for disease refractory to topical therapies. Patients with any stage were eligible. Although the complete response rate was higher with combined therapy, toxic effects were considerably greater, and no difference was seen in disease-free or overall survival between the two groups.[1][Level of evidence: 1iiA]

Treatment options (note that in this clinical setting, the skin is easily injured; any of the topical therapies must be administered with extreme caution):[2,3]

  1. Psoralen and ultraviolet A radiation (PUVA). Therapeutic trials with PUVA have shown a 62% to 90% complete remission rate, with early cutaneous stages achieving the best responses. PUVA may be used in conjunction with systemic treatment. Maintenance therapy with PUVA is generally required to prolong remission duration.[4] PUVA combined with interferon alpha-2a is associated with a high response rate.[5]
  2. TSEB. Electron radiation of appropriate energies will penetrate only to the dermis, and thus the skin alone can be treated without systemic effects. This therapy requires an excellent radiation therapy facility with physics support, considerable technical expertise, and precise dosimetry. The therapy can produce excellent palliation, with complete response rates of as much as 80%.[6,7]
  3. Ultraviolet B radiation.[8]
  4. Symptomatic management with topical corticosteroids.
  5. Local electron-beam radiation or orthovoltage radiation therapy may also be used to palliate areas of bulky or symptomatic disease.[9]
  6. Fludarabine, 2-chlorodeoxyadenosine, and pentostatin are active agents for mycosis fungoides and the Sézary syndrome.[10-13] Chemotherapeutic agents generally demonstrate short durations of response. In a retrospective review of 198 patients with advanced-stage disease, the median time before patients required new therapy was 4 months.[14]
  7. Interferon alpha alone or in combination with topical therapy, as evidenced in ECOG-1495.[11,15] A retrospective review of 198 patients with mycosis fungoides and the Sézary syndrome compared time to next treatment (TTNT) between interferon alpha and conventional chemotherapy. Interferon alpha provided a longer TTNT of 8.7 months (95% confidence interval [CI], 6.0–18.0) than did chemotherapy, with a TTNT of 3.9 months (95% CI, 3.2–5.1) and P < .00001.[14][Level of evidence: 3iiiDiv]
  8. Systemic chemotherapy (single agent or combination) often combined with treatment directed at the skin.[1,16,17] Chemotherapeutic agents generally demonstrate short durations of response. In a retrospective review of 198 patients with advanced-stage disease, the median time before patients required new therapy was 4 months.[14]
  9. Extracorporeal photochemotherapy.[18-20]
  10. Topical mechlorethamine (nitrogen mustard). This form of treatment may be used palliatively or to supplement therapeutic approaches directed against nodal or visceral disease. The overall complete remission rate of TNM classification T4 patients is 20% to 40%. Treatments are usually continued for 2 to 3 years.[21,22]
  11. Bexarotene, an oral or topical retinoid.[23,24]
  12. Oral methotrexate (NCT00425555).[25]
  13. Pegylated liposomal doxorubicin.[26-28] A retrospective review of 198 patients with mycosis fungoides and the Sézary syndrome compared TTNT between histone deacetylase inhibitors (HDACi) and conventional chemotherapy. HDACi provided a longer TTNT of 4.5 months (95% CI, 4.0–6.1) than did chemotherapy, with a TTNT of 3.9 months (95% CI, 3.2–5.1) and P = .01.[14][Level of evidence: 3iiiDiv]
  14. Vorinostat or romidepsin or other HDACi.[3,29-31] A retrospective review of 198 patients with mycosis fungoides and the Sézary syndrome compared TTNT between HDACi and conventional chemotherapy. HDACi provided a longer TTNT of 4.5 months (95% CI, 4.0–6.1) than did chemotherapy with a TTNT of 3.9 months (95% CI, 3.2–5.1) and P = .01.[14][Level of evidence: 3iiiDiv]
  15. Pralatrexate (folate analog).[32,33] Chemotherapeutic agents generally demonstrate short durations of response. In a retrospective review of 198 patients with advanced-stage disease, the median time before patients required new therapy was 4 months.[14]
  16. Alemtuzumab (a humanized monoclonal antibody targeting the CD52 antigen).[3,34]
  17. Lenalidomide.[35]

Current Clinical Trials

Check the list of NCI-supported cancer clinical trials that are now accepting patients with stage III mycosis fungoides/Sezary syndrome. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI website.

References

  1. Kaye FJ, Bunn PA Jr, Steinberg SM, et al.: A randomized trial comparing combination electron-beam radiation and chemotherapy with topical therapy in the initial treatment of mycosis fungoides. N Engl J Med 321 (26): 1784-90, 1989. [PubMed: 2594037]
  2. Trautinger F, Knobler R, Willemze R, et al.: EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome. Eur J Cancer 42 (8): 1014-30, 2006. [PubMed: 16574401]
  3. Olsen EA, Rook AH, Zic J, et al.: Sézary syndrome: immunopathogenesis, literature review of therapeutic options, and recommendations for therapy by the United States Cutaneous Lymphoma Consortium (USCLC). J Am Acad Dermatol 64 (2): 352-404, 2011. [PubMed: 21145619]
  4. Herrmann JJ, Roenigk HH Jr, Hurria A, et al.: Treatment of mycosis fungoides with photochemotherapy (PUVA): long-term follow-up. J Am Acad Dermatol 33 (2 Pt 1): 234-42, 1995. [PubMed: 7622650]
  5. Kuzel TM, Roenigk HH Jr, Samuelson E, et al.: Effectiveness of interferon alfa-2a combined with phototherapy for mycosis fungoides and the Sézary syndrome. J Clin Oncol 13 (1): 257-63, 1995. [PubMed: 7799028]
  6. Jones GW, Rosenthal D, Wilson LD: Total skin electron radiation for patients with erythrodermic cutaneous T-cell lymphoma (mycosis fungoides and the Sézary syndrome). Cancer 85 (9): 1985-95, 1999. [PubMed: 10223240]
  7. Navi D, Riaz N, Levin YS, et al.: The Stanford University experience with conventional-dose, total skin electron-beam therapy in the treatment of generalized patch or plaque (T2) and tumor (T3) mycosis fungoides. Arch Dermatol 147 (5): 561-7, 2011. [PubMed: 21576575]
  8. Elcin G, Duman N, Karahan S, et al.: Long-term follow-up of early mycosis fungoides patients treated with narrowband ultraviolet B phototherapy. J Dermatolog Treat 25 (3): 268-73, 2014. [PubMed: 23030414]
  9. Thomas TO, Agrawal P, Guitart J, et al.: Outcome of patients treated with a single-fraction dose of palliative radiation for cutaneous T-cell lymphoma. Int J Radiat Oncol Biol Phys 85 (3): 747-53, 2013. [PubMed: 22818412]
  10. Saven A, Carrera CJ, Carson DA, et al.: 2-Chlorodeoxyadenosine: an active agent in the treatment of cutaneous T-cell lymphoma. Blood 80 (3): 587-92, 1992. [PubMed: 1353380]
  11. Foss FM, Ihde DC, Breneman DL, et al.: Phase II study of pentostatin and intermittent high-dose recombinant interferon alfa-2a in advanced mycosis fungoides/Sézary syndrome. J Clin Oncol 10 (12): 1907-13, 1992. [PubMed: 1453206]
  12. Foss FM, Ihde DC, Linnoila IR, et al.: Phase II trial of fludarabine phosphate and interferon alfa-2a in advanced mycosis fungoides/Sézary syndrome. J Clin Oncol 12 (10): 2051-9, 1994. [PubMed: 7931473]
  13. Kurzrock R, Pilat S, Duvic M: Pentostatin therapy of T-cell lymphomas with cutaneous manifestations. J Clin Oncol 17 (10): 3117-21, 1999. [PubMed: 10506607]
  14. Hughes CF, Khot A, McCormack C, et al.: Lack of durable disease control with chemotherapy for mycosis fungoides and Sézary syndrome: a comparative study of systemic therapy. Blood 125 (1): 71-81, 2015. [PubMed: 25336628]
  15. Olsen EA, Bunn PA: Interferon in the treatment of cutaneous T-cell lymphoma. Hematol Oncol Clin North Am 9 (5): 1089-107, 1995. [PubMed: 8522486]
  16. Rosen ST, Foss FM: Chemotherapy for mycosis fungoides and the Sézary syndrome. Hematol Oncol Clin North Am 9 (5): 1109-16, 1995. [PubMed: 8522487]
  17. Zackheim HS, Epstein EH Jr: Low-dose methotrexate for the Sézary syndrome. J Am Acad Dermatol 21 (4 Pt 1): 757-62, 1989. [PubMed: 2808792]
  18. Edelson R, Berger C, Gasparro F, et al.: Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy. Preliminary results. N Engl J Med 316 (6): 297-303, 1987. [PubMed: 3543674]
  19. Heald PW, Perez MI, McKiernan G, et al.: Extracorporeal photochemotherapy for CTCL. Prog Clin Biol Res 337: 443-7, 1990. [PubMed: 2191335]
  20. Scarisbrick JJ, Taylor P, Holtick U, et al.: U.K. consensus statement on the use of extracorporeal photopheresis for treatment of cutaneous T-cell lymphoma and chronic graft-versus-host disease. Br J Dermatol 158 (4): 659-78, 2008. [PubMed: 18241274]
  21. Lessin SR, Duvic M, Guitart J, et al.: Topical chemotherapy in cutaneous T-cell lymphoma: positive results of a randomized, controlled, multicenter trial testing the efficacy and safety of a novel mechlorethamine, 0.02%, gel in mycosis fungoides. JAMA Dermatol 149 (1): 25-32, 2013. [PMC free article: PMC3662469] [PubMed: 23069814]
  22. de Quatrebarbes J, Estève E, Bagot M, et al.: Treatment of early-stage mycosis fungoides with twice-weekly applications of mechlorethamine and topical corticosteroids: a prospective study. Arch Dermatol 141 (9): 1117-20, 2005. [PubMed: 16172308]
  23. Duvic M, Hymes K, Heald P, et al.: Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: multinational phase II-III trial results. J Clin Oncol 19 (9): 2456-71, 2001. [PubMed: 11331325]
  24. Heald P, Mehlmauer M, Martin AG, et al.: Topical bexarotene therapy for patients with refractory or persistent early-stage cutaneous T-cell lymphoma: results of the phase III clinical trial. J Am Acad Dermatol 49 (5): 801-15, 2003. [PubMed: 14576658]
  25. Zackheim HS, Kashani-Sabet M, McMillan A: Low-dose methotrexate to treat mycosis fungoides: a retrospective study in 69 patients. J Am Acad Dermatol 49 (5): 873-8, 2003. [PubMed: 14576667]
  26. Dummer R, Quaglino P, Becker JC, et al.: Prospective international multicenter phase II trial of intravenous pegylated liposomal doxorubicin monochemotherapy in patients with stage IIB, IVA, or IVB advanced mycosis fungoides: final results from EORTC 21012. J Clin Oncol 30 (33): 4091-7, 2012. [PubMed: 23045580]
  27. Wollina U, Dummer R, Brockmeyer NH, et al.: Multicenter study of pegylated liposomal doxorubicin in patients with cutaneous T-cell lymphoma. Cancer 98 (5): 993-1001, 2003. [PubMed: 12942567]
  28. Quereux G, Marques S, Nguyen JM, et al.: Prospective multicenter study of pegylated liposomal doxorubicin treatment in patients with advanced or refractory mycosis fungoides or Sézary syndrome. Arch Dermatol 144 (6): 727-33, 2008. [PubMed: 18559761]
  29. Duvic M, Dummer R, Becker JC, et al.: Panobinostat activity in both bexarotene-exposed and -naïve patients with refractory cutaneous T-cell lymphoma: results of a phase II trial. Eur J Cancer 49 (2): 386-94, 2013. [PubMed: 22981498]
  30. Olsen EA, Kim YH, Kuzel TM, et al.: Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma. J Clin Oncol 25 (21): 3109-15, 2007. [PubMed: 17577020]
  31. Piekarz RL, Frye R, Turner M, et al.: Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma. J Clin Oncol 27 (32): 5410-7, 2009. [PMC free article: PMC2773225] [PubMed: 19826128]
  32. Horwitz SM, Kim YH, Foss F, et al.: Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood 119 (18): 4115-22, 2012. [PubMed: 22394596]
  33. Talpur R, Thompson A, Gangar P, et al.: Pralatrexate alone or in combination with bexarotene: long-term tolerability in relapsed/refractory mycosis fungoides. Clin Lymphoma Myeloma Leuk 14 (4): 297-304, 2014. [PubMed: 24589156]
  34. de Masson A, Guitera P, Brice P, et al.: Long-term efficacy and safety of alemtuzumab in advanced primary cutaneous T-cell lymphomas. Br J Dermatol 170 (3): 720-4, 2014. [PubMed: 24438061]
  35. Querfeld C, Rosen ST, Guitart J, et al.: Results of an open-label multicenter phase 2 trial of lenalidomide monotherapy in refractory mycosis fungoides and Sézary syndrome. Blood 123 (8): 1159-66, 2014. [PubMed: 24335103]

Stage IV Mycosis Fungoides and the Sézary Syndrome

The use of single alkylating agents has produced objective responses in 60% of patients, with a duration of less than 6 months. One of the alkylating agents (e.g., mechlorethamine, cyclophosphamide, or chlorambucil), or the antimetabolite methotrexate is the most frequently used. Single agents have not been shown to cure any patients, and insufficient data exist to determine whether these agents prolong survival. Combination chemotherapy is not definitely superior to single agents. Even in stage IV disease, treatments directed at the skin may provide significant palliation.

A randomized study of 103 patients compared combined total-skin electron-beam radiation (TSEB) plus combination chemotherapy with conservation therapy consisting of sequential topical therapies.[1] In the latter group, combination chemotherapy was reserved for symptomatic extracutaneous disease or for disease refractory to topical therapies. Patients with any stage were eligible. Although the complete response rate was higher with combined therapy, toxic effects were considerably greater, and no difference was seen in disease-free survival or overall survival between the two groups.[1][Level of evidence: 1iiA]

Treatment options:[2,3]

  1. Psoralen and ultraviolet A radiation (PUVA). Therapeutic trials with PUVA have shown a 62% to 90% complete remission rate, with early cutaneous stages achieving the best responses. PUVA may be used in conjunction with systemic treatment. Maintenance therapy with PUVA is generally required to prolong remission duration.[4] PUVA combined with interferon alpha-2a is associated with a high response rate.[5]
  2. TSEB. Electron radiation of appropriate energies will penetrate only to the dermis, and the skin alone can be treated without systemic effects. This therapy requires an excellent radiation therapy facility with physics support, considerable technical expertise, and precise dosimetry. This therapy can produce excellent palliation and may be combined with systemic treatment.[6,7]
  3. Ultraviolet B radiation.[8]
  4. Symptomatic management with topical corticosteroids.
  5. Local electron-beam radiation or orthovoltage radiation therapy may also be used to palliate areas of bulky or symptomatic disease.[9]
  6. Fludarabine, 2-chlorodeoxyadenosine, and pentostatin are active agents for mycosis fungoides and Sézary syndrome.[10-12] Chemotherapeutic agents generally demonstrate short durations of response. In a retrospective review of 198 patients with advanced-stage disease, the median time before patients required new therapy was 4 months.[13]
  7. Interferon alpha alone or in combination with topical therapy, as evidenced in the ECOG-1495 trial.[11,14] A retrospective review of 198 patients with mycosis fungoides and the Sézary syndrome compared time to next treatment (TTNT) between interferon alpha and conventional chemotherapy. Interferon alpha provided a longer TTNT of 8.7 months (95% confidence interval [CI], 6.0–18.0) than did chemotherapy, with a TTNT of 3.9 months (95% CI, 3.2–5.1) and P < .00001.[13][Level of evidence: 3iiiDiv]
  8. Systemic chemotherapy: chlorambucil plus prednisone, mechlorethamine, cyclophosphamide, methotrexate, and combination chemotherapy.[1,15,16] Chemotherapeutic agents generally demonstrate short durations of response. In a retrospective review of 198 patients with advanced-stage disease, the median time before patients required new therapy was 4 months.[13]
  9. Topical mechlorethamine (nitrogen mustard). This form of treatment may be used palliatively or to supplement therapeutic approaches directed against nodal or visceral disease. The overall complete remission rate in 243 patients was 64% and was related to stage; as many as 35% of stage IV patients had complete responses. Treatments are usually continued for 2 to 3 years.[17,18]
  10. Extracorporeal photochemotherapy alone [19-22] or in combination with TSEB.[23]
  11. Serotherapy with monoclonal antibodies.[24,25]
  12. Bexarotene, an oral or topical retinoid.[26,27]
  13. Oral methotrexate (NCT00425555).[28]
  14. Pegylated liposomal doxorubicin.[29-31] A retrospective review of 198 patients with mycosis fungoides and the Sézary syndrome compared TTNT between histone deacetylase inhibitors (HDACi) and conventional chemotherapy. HDACi provided a longer TTNT of 4.5 months (95% CI, 4.0–6.1) than did chemotherapy, with a TTNT of 3.9 months (95% CI, 3.2–5.1) and P = .01.[13][Level of evidence: 3iiiDiv]
  15. Vorinostat or romidepsin or other HDACi.[32-34] A retrospective review of 198 patients with mycosis fungoides and the Sézary syndrome compared TTNT between HDACi and conventional chemotherapy. HDACi provided a longer TTNT of 4.5 months (95% CI, 4.0–6.1) than did chemotherapy with a TTNT of 3.9 months (95% CI, 3.2–5.1) and P = .01.[13][Level of evidence: 3iiiDiv]
  16. Pralatrexate (folate analog).[35,36] Chemotherapeutic agents generally demonstrate short durations of response. In a retrospective review of 198 patients with advanced-stage disease, the median time before patients required new therapy was 4 months.[13]
  17. Alemtuzumab (a humanized monoclonal antibody targeting the CD52 antigen).[37,38]
  18. Lenalidomide.[39]

Current Clinical Trials

Check the list of NCI-supported cancer clinical trials that are now accepting patients with stage IV mycosis fungoides/Sezary syndrome. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI website.

References

  1. Kaye FJ, Bunn PA Jr, Steinberg SM, et al.: A randomized trial comparing combination electron-beam radiation and chemotherapy with topical therapy in the initial treatment of mycosis fungoides. N Engl J Med 321 (26): 1784-90, 1989. [PubMed: 2594037]
  2. Trautinger F, Knobler R, Willemze R, et al.: EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome. Eur J Cancer 42 (8): 1014-30, 2006. [PubMed: 16574401]
  3. Prince HM, Duvic M, Martin A, et al.: Phase III placebo-controlled trial of denileukin diftitox for patients with cutaneous T-cell lymphoma. J Clin Oncol 28 (11): 1870-7, 2010. [PubMed: 20212249]
  4. Herrmann JJ, Roenigk HH Jr, Hurria A, et al.: Treatment of mycosis fungoides with photochemotherapy (PUVA): long-term follow-up. J Am Acad Dermatol 33 (2 Pt 1): 234-42, 1995. [PubMed: 7622650]
  5. Kuzel TM, Roenigk HH Jr, Samuelson E, et al.: Effectiveness of interferon alfa-2a combined with phototherapy for mycosis fungoides and the Sézary syndrome. J Clin Oncol 13 (1): 257-63, 1995. [PubMed: 7799028]
  6. Jones GW, Rosenthal D, Wilson LD: Total skin electron radiation for patients with erythrodermic cutaneous T-cell lymphoma (mycosis fungoides and the Sézary syndrome). Cancer 85 (9): 1985-95, 1999. [PubMed: 10223240]
  7. Navi D, Riaz N, Levin YS, et al.: The Stanford University experience with conventional-dose, total skin electron-beam therapy in the treatment of generalized patch or plaque (T2) and tumor (T3) mycosis fungoides. Arch Dermatol 147 (5): 561-7, 2011. [PubMed: 21576575]
  8. Elcin G, Duman N, Karahan S, et al.: Long-term follow-up of early mycosis fungoides patients treated with narrowband ultraviolet B phototherapy. J Dermatolog Treat 25 (3): 268-73, 2014. [PubMed: 23030414]
  9. Thomas TO, Agrawal P, Guitart J, et al.: Outcome of patients treated with a single-fraction dose of palliative radiation for cutaneous T-cell lymphoma. Int J Radiat Oncol Biol Phys 85 (3): 747-53, 2013. [PubMed: 22818412]
  10. Saven A, Carrera CJ, Carson DA, et al.: 2-Chlorodeoxyadenosine: an active agent in the treatment of cutaneous T-cell lymphoma. Blood 80 (3): 587-92, 1992. [PubMed: 1353380]
  11. Foss FM, Ihde DC, Breneman DL, et al.: Phase II study of pentostatin and intermittent high-dose recombinant interferon alfa-2a in advanced mycosis fungoides/Sézary syndrome. J Clin Oncol 10 (12): 1907-13, 1992. [PubMed: 1453206]
  12. Foss FM, Ihde DC, Linnoila IR, et al.: Phase II trial of fludarabine phosphate and interferon alfa-2a in advanced mycosis fungoides/Sézary syndrome. J Clin Oncol 12 (10): 2051-9, 1994. [PubMed: 7931473]
  13. Hughes CF, Khot A, McCormack C, et al.: Lack of durable disease control with chemotherapy for mycosis fungoides and Sézary syndrome: a comparative study of systemic therapy. Blood 125 (1): 71-81, 2015. [PubMed: 25336628]
  14. Olsen EA, Bunn PA: Interferon in the treatment of cutaneous T-cell lymphoma. Hematol Oncol Clin North Am 9 (5): 1089-107, 1995. [PubMed: 8522486]
  15. Rosen ST, Foss FM: Chemotherapy for mycosis fungoides and the Sézary syndrome. Hematol Oncol Clin North Am 9 (5): 1109-16, 1995. [PubMed: 8522487]
  16. Zackheim HS, Epstein EH Jr: Low-dose methotrexate for the Sézary syndrome. J Am Acad Dermatol 21 (4 Pt 1): 757-62, 1989. [PubMed: 2808792]
  17. Lessin SR, Duvic M, Guitart J, et al.: Topical chemotherapy in cutaneous T-cell lymphoma: positive results of a randomized, controlled, multicenter trial testing the efficacy and safety of a novel mechlorethamine, 0.02%, gel in mycosis fungoides. JAMA Dermatol 149 (1): 25-32, 2013. [PMC free article: PMC3662469] [PubMed: 23069814]
  18. de Quatrebarbes J, Estève E, Bagot M, et al.: Treatment of early-stage mycosis fungoides with twice-weekly applications of mechlorethamine and topical corticosteroids: a prospective study. Arch Dermatol 141 (9): 1117-20, 2005. [PubMed: 16172308]
  19. Edelson R, Berger C, Gasparro F, et al.: Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy. Preliminary results. N Engl J Med 316 (6): 297-303, 1987. [PubMed: 3543674]
  20. Heald PW, Perez MI, McKiernan G, et al.: Extracorporeal photochemotherapy for CTCL. Prog Clin Biol Res 337: 443-7, 1990. [PubMed: 2191335]
  21. Fraser-Andrews E, Seed P, Whittaker S, et al.: Extracorporeal photopheresis in Sézary syndrome. No significant effect in the survival of 44 patients with a peripheral blood T-cell clone. Arch Dermatol 134 (8): 1001-5, 1998. [PubMed: 9722731]
  22. Scarisbrick JJ, Taylor P, Holtick U, et al.: U.K. consensus statement on the use of extracorporeal photopheresis for treatment of cutaneous T-cell lymphoma and chronic graft-versus-host disease. Br J Dermatol 158 (4): 659-78, 2008. [PubMed: 18241274]
  23. Palareti G, Maccaferri M, Manotti C, et al.: Fibrinogen assays: a collaborative study of six different methods. C.I.S.M.E.L. Comitato Italiano per la Standardizzazione dei Metodi in Ematologia e Laboratorio. Clin Chem 37 (5): 714-9, 1991. [PubMed: 2032326]
  24. Knox SJ, Levy R, Hodgkinson S, et al.: Observations on the effect of chimeric anti-CD4 monoclonal antibody in patients with mycosis fungoides. Blood 77 (1): 20-30, 1991. [PubMed: 1984796]
  25. Rosen ST, Zimmer AM, Goldman-Leikin R, et al.: Radioimmunodetection and radioimmunotherapy of cutaneous T cell lymphomas using an 131I-labeled monoclonal antibody: an Illinois Cancer Council Study. J Clin Oncol 5 (4): 562-73, 1987. [PubMed: 3549989]
  26. Duvic M, Hymes K, Heald P, et al.: Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: multinational phase II-III trial results. J Clin Oncol 19 (9): 2456-71, 2001. [PubMed: 11331325]
  27. Heald P, Mehlmauer M, Martin AG, et al.: Topical bexarotene therapy for patients with refractory or persistent early-stage cutaneous T-cell lymphoma: results of the phase III clinical trial. J Am Acad Dermatol 49 (5): 801-15, 2003. [PubMed: 14576658]
  28. Zackheim HS, Kashani-Sabet M, McMillan A: Low-dose methotrexate to treat mycosis fungoides: a retrospective study in 69 patients. J Am Acad Dermatol 49 (5): 873-8, 2003. [PubMed: 14576667]
  29. Dummer R, Quaglino P, Becker JC, et al.: Prospective international multicenter phase II trial of intravenous pegylated liposomal doxorubicin monochemotherapy in patients with stage IIB, IVA, or IVB advanced mycosis fungoides: final results from EORTC 21012. J Clin Oncol 30 (33): 4091-7, 2012. [PubMed: 23045580]
  30. Wollina U, Dummer R, Brockmeyer NH, et al.: Multicenter study of pegylated liposomal doxorubicin in patients with cutaneous T-cell lymphoma. Cancer 98 (5): 993-1001, 2003. [PubMed: 12942567]
  31. Quereux G, Marques S, Nguyen JM, et al.: Prospective multicenter study of pegylated liposomal doxorubicin treatment in patients with advanced or refractory mycosis fungoides or Sézary syndrome. Arch Dermatol 144 (6): 727-33, 2008. [PubMed: 18559761]
  32. Duvic M, Dummer R, Becker JC, et al.: Panobinostat activity in both bexarotene-exposed and -naïve patients with refractory cutaneous T-cell lymphoma: results of a phase II trial. Eur J Cancer 49 (2): 386-94, 2013. [PubMed: 22981498]
  33. Olsen EA, Kim YH, Kuzel TM, et al.: Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma. J Clin Oncol 25 (21): 3109-15, 2007. [PubMed: 17577020]
  34. Piekarz RL, Frye R, Turner M, et al.: Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma. J Clin Oncol 27 (32): 5410-7, 2009. [PMC free article: PMC2773225] [PubMed: 19826128]
  35. Horwitz SM, Kim YH, Foss F, et al.: Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood 119 (18): 4115-22, 2012. [PubMed: 22394596]
  36. Talpur R, Thompson A, Gangar P, et al.: Pralatrexate alone or in combination with bexarotene: long-term tolerability in relapsed/refractory mycosis fungoides. Clin Lymphoma Myeloma Leuk 14 (4): 297-304, 2014. [PubMed: 24589156]
  37. Olsen EA, Rook AH, Zic J, et al.: Sézary syndrome: immunopathogenesis, literature review of therapeutic options, and recommendations for therapy by the United States Cutaneous Lymphoma Consortium (USCLC). J Am Acad Dermatol 64 (2): 352-404, 2011. [PubMed: 21145619]
  38. de Masson A, Guitera P, Brice P, et al.: Long-term efficacy and safety of alemtuzumab in advanced primary cutaneous T-cell lymphomas. Br J Dermatol 170 (3): 720-4, 2014. [PubMed: 24438061]
  39. Querfeld C, Rosen ST, Guitart J, et al.: Results of an open-label multicenter phase 2 trial of lenalidomide monotherapy in refractory mycosis fungoides and Sézary syndrome. Blood 123 (8): 1159-66, 2014. [PubMed: 24335103]

Recurrent Mycosis Fungoides and the Sézary Syndrome

The treatment of relapsed patients with cutaneous T-cell lymphomas involves the joint decisions of the dermatologist, medical oncologist, and radiation oncologist. It may be possible to re-treat localized areas of relapse in the skin with additional electron-beam radiation or possibly to repeat total-skin electron-beam radiation therapy (TSEB).[1] Photon radiation to bulky skin or nodal masses may prove beneficial. If these options are not possible, then continued topical treatment with other modalities such as mechlorethamine or psoralen and ultraviolet A radiation (PUVA) may be warranted to relieve cutaneous symptoms.

Clinical trials, if possible, should be considered as the next therapeutic option. Options under clinical evaluation for recurrent mycosis fungoides and the Sézary syndrome include the following:[2,3]

  1. Additional electron-beam radiation or a repeat of TSEB.
  2. Photon radiation to bulky skin or nodal masses.[4]
  3. Topical treatment with mechlorethamine or PUVA.
  4. PUVA combined with interferon alpha-2a is associated with a high response rate.[5]
  5. Ultraviolet B radiation.[6]
  6. Symptomatic management with topical corticosteroids.
  7. Extracorporeal photochemotherapy has produced tumor regression in patients resistant to other therapies.[7,8]
  8. Bexarotene is a retinoid available in an oral or topical form.[9,10]
  9. Allogeneic or autologous bone marrow transplantation.[11-15]
  10. Vorinostat or romidepsin or other histone deacetylase inhibitors (HDACi).[16-18] A retrospective review of 198 patients with mycosis fungoides and the Sézary syndrome compared TTNT between HDACi and conventional chemotherapy. HDACi provided a longer TTNT of 4.5 months (95% confidence interval [CI], 4.0–6.1) than did chemotherapy with a TTNT of 3.9 months (95% CI, 3.2–5.1) and P = .01.[19][Level of evidence: 3iiiDiv]
  11. Pralatrexate (folate analog).[20,21] Chemotherapeutic agents generally demonstrate short durations of response. In a retrospective review of 198 patients with advance-stage disease, the median time before patients required new therapy was 4 months.[19]
  12. Lenalidomide.[22]
  13. Pegylated liposomal doxorubicin.[23-25] A retrospective review of 198 patients with mycosis fungoides and the Sézary syndrome compared TTNT between HDACi and conventional chemotherapy. HDACi provided a longer TTNT of 4.5 months (95% CI, 4.0–6.1) than did chemotherapy with a TTNT of 3.9 months (95% CI, 3.2–5.1) and P = .01.[19][Level of evidence: 3iiiDiv]

Current Clinical Trials

Check the list of NCI-supported cancer clinical trials that are now accepting patients with recurrent mycosis fungoides/Sezary syndrome. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI website.

References

  1. Becker M, Hoppe RT, Knox SJ: Multiple courses of high-dose total skin electron beam therapy in the management of mycosis fungoides. Int J Radiat Oncol Biol Phys 32 (5): 1445-9, 1995. [PubMed: 7635786]
  2. Trautinger F, Knobler R, Willemze R, et al.: EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome. Eur J Cancer 42 (8): 1014-30, 2006. [PubMed: 16574401]
  3. Prince HM, Duvic M, Martin A, et al.: Phase III placebo-controlled trial of denileukin diftitox for patients with cutaneous T-cell lymphoma. J Clin Oncol 28 (11): 1870-7, 2010. [PubMed: 20212249]
  4. Thomas TO, Agrawal P, Guitart J, et al.: Outcome of patients treated with a single-fraction dose of palliative radiation for cutaneous T-cell lymphoma. Int J Radiat Oncol Biol Phys 85 (3): 747-53, 2013. [PubMed: 22818412]
  5. Kuzel TM, Roenigk HH Jr, Samuelson E, et al.: Effectiveness of interferon alfa-2a combined with phototherapy for mycosis fungoides and the Sézary syndrome. J Clin Oncol 13 (1): 257-63, 1995. [PubMed: 7799028]
  6. Elcin G, Duman N, Karahan S, et al.: Long-term follow-up of early mycosis fungoides patients treated with narrowband ultraviolet B phototherapy. J Dermatolog Treat 25 (3): 268-73, 2014. [PubMed: 23030414]
  7. Edelson R, Berger C, Gasparro F, et al.: Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy. Preliminary results. N Engl J Med 316 (6): 297-303, 1987. [PubMed: 3543674]
  8. Heald PW, Perez MI, McKiernan G, et al.: Extracorporeal photochemotherapy for CTCL. Prog Clin Biol Res 337: 443-7, 1990. [PubMed: 2191335]
  9. Miller VA, Benedetti FM, Rigas JR, et al.: Initial clinical trial of a selective retinoid X receptor ligand, LGD1069. J Clin Oncol 15 (2): 790-5, 1997. [PubMed: 9053506]
  10. Duvic M, Hymes K, Heald P, et al.: Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: multinational phase II-III trial results. J Clin Oncol 19 (9): 2456-71, 2001. [PubMed: 11331325]
  11. Molina A, Zain J, Arber DA, et al.: Durable clinical, cytogenetic, and molecular remissions after allogeneic hematopoietic cell transplantation for refractory Sezary syndrome and mycosis fungoides. J Clin Oncol 23 (25): 6163-71, 2005. [PubMed: 16135483]
  12. Duvic M, Donato M, Dabaja B, et al.: Total skin electron beam and non-myeloablative allogeneic hematopoietic stem-cell transplantation in advanced mycosis fungoides and Sezary syndrome. J Clin Oncol 28 (14): 2365-72, 2010. [PubMed: 20351328]
  13. Duarte RF, Canals C, Onida F, et al.: Allogeneic hematopoietic cell transplantation for patients with mycosis fungoides and Sézary syndrome: a retrospective analysis of the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol 28 (29): 4492-9, 2010. [PubMed: 20697072]
  14. Schlaak M, Pickenhain J, Theurich S, et al.: Allogeneic stem cell transplantation versus conventional therapy for advanced primary cutaneous T-cell lymphoma. Cochrane Database Syst Rev 1: CD008908, 2012. [PubMed: 22258991]
  15. Duarte RF, Boumendil A, Onida F, et al.: Long-term outcome of allogeneic hematopoietic cell transplantation for patients with mycosis fungoides and Sézary syndrome: a European society for blood and marrow transplantation lymphoma working party extended analysis. J Clin Oncol 32 (29): 3347-8, 2014. [PubMed: 25154828]
  16. Duvic M, Dummer R, Becker JC, et al.: Panobinostat activity in both bexarotene-exposed and -naïve patients with refractory cutaneous T-cell lymphoma: results of a phase II trial. Eur J Cancer 49 (2): 386-94, 2013. [PubMed: 22981498]
  17. Olsen EA, Kim YH, Kuzel TM, et al.: Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma. J Clin Oncol 25 (21): 3109-15, 2007. [PubMed: 17577020]
  18. Piekarz RL, Frye R, Turner M, et al.: Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma. J Clin Oncol 27 (32): 5410-7, 2009. [PMC free article: PMC2773225] [PubMed: 19826128]
  19. Hughes CF, Khot A, McCormack C, et al.: Lack of durable disease control with chemotherapy for mycosis fungoides and Sézary syndrome: a comparative study of systemic therapy. Blood 125 (1): 71-81, 2015. [PubMed: 25336628]
  20. Horwitz SM, Kim YH, Foss F, et al.: Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood 119 (18): 4115-22, 2012. [PubMed: 22394596]
  21. Talpur R, Thompson A, Gangar P, et al.: Pralatrexate alone or in combination with bexarotene: long-term tolerability in relapsed/refractory mycosis fungoides. Clin Lymphoma Myeloma Leuk 14 (4): 297-304, 2014. [PubMed: 24589156]
  22. Querfeld C, Rosen ST, Guitart J, et al.: Results of an open-label multicenter phase 2 trial of lenalidomide monotherapy in refractory mycosis fungoides and Sézary syndrome. Blood 123 (8): 1159-66, 2014. [PubMed: 24335103]
  23. Dummer R, Quaglino P, Becker JC, et al.: Prospective international multicenter phase II trial of intravenous pegylated liposomal doxorubicin monochemotherapy in patients with stage IIB, IVA, or IVB advanced mycosis fungoides: final results from EORTC 21012. J Clin Oncol 30 (33): 4091-7, 2012. [PubMed: 23045580]
  24. Wollina U, Dummer R, Brockmeyer NH, et al.: Multicenter study of pegylated liposomal doxorubicin in patients with cutaneous T-cell lymphoma. Cancer 98 (5): 993-1001, 2003. [PubMed: 12942567]
  25. Quereux G, Marques S, Nguyen JM, et al.: Prospective multicenter study of pegylated liposomal doxorubicin treatment in patients with advanced or refractory mycosis fungoides or Sézary syndrome. Arch Dermatol 144 (6): 727-33, 2008. [PubMed: 18559761]

Changes to This Summary (12/23/2015)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

General Information About Mycosis Fungoides and the Sézary Syndrome

Added Kadin et al. as reference 19.

Stage Information for Mycosis Fungoides and the Sézary Syndrome

Added text to state that recent clinical trials assess the extent of skin involvement using detailed scoring systems such as the modified Severity Weighted Assessment Tool (cited 2011 Olsen et al. as reference 4).

Stage I Mycosis Fungoides

Added Elcin et al. as reference 13. Added Foss et al. as reference 17 and 1995 Olsen et al. as reference 18. Also added that a retrospective review of 198 patients with mycosis fungoides and the Sézary syndrome compared time to next treatment (TTNT) between interferon alpha and conventional chemotherapy (cited Hughes et al. as reference 19 and level of evidence 3iiiDiv). Added that a retrospective review of 198 patients with mycosis fungoides and the Sézary syndrome compared TTNT between histone deacetylase inhibitors (HDACi) and conventional chemotherapy (added level of evidence 3iiiDiv). Added Talpur et al. as reference 28. Added lenalidomide as a treatment option for stage I mycosis fungoides and the Sézary syndrome (cited Querfeld et al. as reference 29).

Stage II Mycosis Fungoides

Added Elcin et al. as reference 10. Added 1995 Olsen et al. as reference 15. Also added text to state that a retrospective review of 198 patients with mycosis fungoides and the Sézary syndrome compared TTNT between interferon alpha and conventional chemotherapy (cited Hughes et al. as reference 16 and level of evidence 3iiiDiv). Added that a retrospective review of 198 patients with mycosis fungoides and the Sézary syndrome compared TTNT between HDACi and conventional chemotherapy (added level of evidence 3iiiDiv). Added Talpur et al. as reference 27. Added lenalidomide as a treatment option for stage II mycosis fungoides and the Sézary syndrome (cited Querfeld et al. as reference 28).

Stage III Mycosis Fungoides

Added Elcin et al. as reference 8. Added text to state that chemotherapeutic agents generally demonstrate short durations of response; in a retrospective review of 198 patients with advanced-stage disease, the median time before patients required new therapy was 4 months (cited Hughes et al. as reference 14). Also added that a retrospective review of 198 patients with mycosis fungoides and the Sézary syndrome compared TTNT between interferon alpha and conventional chemotherapy (added level of evidence 3iiiDiv). Added that a retrospective review of 198 patients with mycosis fungoides and the Sézary syndrome compared TTNT between HDACi and conventional chemotherapy (added level of evidence 3iiiDiv). Added Talpur et al. as reference 33. Added lenalidomide as a treatment option for stage III mycosis fungoides and the Sézary syndrome (cited Querfeld et al. as reference 35).

Stage IV Mycosis Fungoides and the Sézary Syndrome

Added Elcin et al. as reference 8. Added text to state that chemotherapeutic agents generally demonstrate short durations of response; in a retrospective review of 198 patients with advanced-stage disease, the median time before patient required new therapy was 4 months (cited Hughes et al. as reference 13). Also added that a retrospective review of 198 patients with mycosis fungoides and the Sézary syndrome compared TTNT between interferon alpha and conventional chemotherapy (added level of evidence 3iiiDiv). Added that chemotherapeutic agents generally demonstrate short durations of response; in a retrospective review of 198 patients with advanced-stage disease, the median time before patients required new therapy was 4 months. Added that a retrospective review of 198 patients with mycosis fungoides and the Sézary syndrome compared TTNT between HDACi and conventional chemotherapy (added level of evidence 3iiiDiv). Added Talpur et al. as reference 36. Added lenalidomide as a treatment option for stage IV mycosis fungoides and the Sézary syndrome (cited Querfeld et al. as reference 39).

Recurrent Mycosis Fungoides and the Sézary Syndrome

Added Elcin et al. as reference 6. Added that a retrospective review of 198 patients with mycosis fungoides and the Sézary syndrome compared TTNT between HDACi and conventional chemotherapy (cited Hughes et al. as reference 19 and level of evidence 3iiiDiv). Added Talpur et al. as reference 21. Added that chemotherapeutic agents generally demonstrate short durations of response; in a retrospective review of 198 patients with advanced-stage disease, the median time before patients required new therapy was 4 months. Added lenalidomide as a treatment option for recurrent mycosis fungoides and the Sézary syndrome (cited Querfeld et al. as reference 22). Added pegylated liposomal doxorubicin as a treatment option (cited Dummer et al. as reference 23, Wollina et al. as reference 24, and Quereux et al. as reference 25).

This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of mycosis fungoides and the Sézary Syndrome. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

  • be discussed at a meeting,
  • be cited with text, or
  • replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewer for Mycosis Fungoides and the Sézary Syndrome Treatment is:

  • Eric J. Seifter, MD (Johns Hopkins University)

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Permission to Use This Summary

PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”

The preferred citation for this PDQ summary is:

National Cancer Institute: PDQ® Mycosis Fungoides and the Sézary Syndrome Treatment. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://www.cancer.gov/types/lymphoma/hp/mycosis-fungoides-treatment-pdq. Accessed <MM/DD/YYYY>.

Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.

Disclaimer

Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.

Contact Us

More information about contacting us or receiving help with the Cancer.gov website can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the website’s Email Us.

Copyright Notice
Bookshelf ID: NBK65849PMID: 26389288

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