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

  • Louise Photiou
  • Carrie van der Weyden
  • Christopher McCormack
  • H. Miles Prince
Lymphomas (MR Smith, Section Editor)
  • 212 Downloads
Part of the following topical collections:
  1. Topical Collection on Lymphomas

Abstract

Purpose of Review

Cutaneous T-cell lymphoma (CTCL) is a rare form of non-Hodgkin lymphoma. Globally, the most common subtypes of CTCL are mycosis fungoides and Sézary syndrome. CTCL can confer significant morbidity and even mortality in advanced disease. Here we review the current and potential future treatments for advanced-stage CTCL.

Recent findings

Heterogeneity of treatment choice has been demonstrated both in US and non-US centers. Systemic treatment choice is currently guided by prognostic features, incorporating stage, immunophenotypic and molecular findings, and patient-specific factors such as age and comorbidities. Randomized controlled studies are uncommon, and the literature is composed predominantly of retrospective, cohort, and early-phase studies. International consensus guidelines are available; however, the lack of comparative trials means that there is no clear algorithmic approach to treatment.

Summary

This review article reports on the systemic treatment options in current use for advanced CTCL, and on the possible future therapies, acknowledging that an algorithmic approach is not yet forthcoming to guide treatment prioritization.

Keywords

Cutaneous T-cell lymphoma Mycosis fungoides Sézary syndrome Bexarotene Extracorporeal photopheresis Interferon-alfa Methotrexate Brentuximab vedotin Mogamulizumab Allogeneic stem cell transplant Vorinostat Romidepsin Denileukin diftitox Doxorubicin Gemcitabine Pentostatin Bendamustine Monoclonal antibodies Histone deacetylase inhibitors Pralatrexate 

Notes

Compliance with Ethical Standards

Conflict of Interest

Louise Photiou declares that she has no conflict of interest.

Carrie van der Weyden declares that she has no conflict of interest.

Christopher McCormack has received compensation from Takeda Pharmaceuticals and MSD for participation on advisory boards.

H. Miles Prince has received research funding through grants from Celgene, Takeda, Amgen, Novartis, Innate Pharma, and Eisai; has received honoraria from Celgene, Takeda, Amgen, Novartis, Innate Pharma, and Eisai; and has participated on advisory boards for Celgene, Takeda, Amgen, Novartis, Innate Pharma, and Eisai.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Willemze R, Jaffe ES, Burg G, Cerroni L, Berti E, Swerdlow SH, et al. WHO-EORTC classification for cutaneous lymphomas. Blood. 2005;105(10):3768–85.PubMedCrossRefGoogle Scholar
  2. 2.
    Criscione VD, Weinstock MA. Incidence of cutaneous T-cell lymphoma in the United States, 1973-2002. Arch Dermatol. 2007;143(7):854–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Bradford PT, Devesa SS, Anderson WF, Toro JR. Cutaneous lymphoma incidence patterns in the United States: a population-based study of 3883 cases. Blood. 2009;113(21):5064–73.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Jawed SI, et al. Primary cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome): part II. Prognosis, management, and future directions. J Am Acad Dermatol. 2014;70(2):223.el–17. quiz 240-2.CrossRefGoogle Scholar
  5. 5.
    Boulos S, Vaid R, Aladily TN, Ivan DS, Talpur R, Duvic M. Clinical presentation, immunopathology, and treatment of juvenile-onset mycosis fungoides: a case series of 34 patients. J Am Acad Dermatol. 2014;71(6):1117–26.PubMedCrossRefGoogle Scholar
  6. 6.
    Bunn PA Jr, Lamberg SI. Report of the committee on staging and classification of cutaneous T-cell lymphomas. Cancer Treat Rep. 1979;63(4):725–8.PubMedGoogle Scholar
  7. 7.
    Olsen E, Vonderheid E, Pimpinelli N, Willemze R, Kim Y, Knobler R, et al. Revisions to the staging and classification of mycosis fungoides and Sézary 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. 2007;110(6):1713–22.PubMedCrossRefGoogle Scholar
  8. 8.
    Willemze R, et al. Primary cutaneous lymphomas: ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up. Ann Oncol. 2013;24(Suppl 6):vi149–54.PubMedCrossRefGoogle Scholar
  9. 9.
    Kim YH, Liu HL, Mraz-Gernhard S, Varghese A, Hoppe RT. Long-term outcome of 525 patients with mycosis fungoides and Sézary syndrome: clinical prognostic factors and risk for disease progression. Arch Dermatol. 2003;139(7):857–66.PubMedCrossRefGoogle Scholar
  10. 10.
    Agar NS, Wedgeworth E, Crichton S, Mitchell TJ, Cox M, Ferreira 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. 2010;28(31):4730–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Arulogun SO, Prince HM, Ng J, Lade S, Ryan GF, Blewitt O, et al. Long-term outcomes of patients with advanced-stage cutaneous T-cell lymphoma and large cell transformation. Blood. 2008;112(8):3082–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Whittaker S, Hoppe R, Prince HM. How I treat mycosis fungoides and Sézary syndrome. Blood. 2016;127(25):3142–53.PubMedCrossRefGoogle Scholar
  13. 13.
    Chung CG, Poligone B. Cutaneous T-cell lymphoma: an update on pathogenesis and systemic therapy. Curr Hematol Malig Rep. 2015;10(4):468–76.PubMedCrossRefGoogle Scholar
  14. 14.
    Campbell JJ, Clark RA, Watanabe R, Kupper TS. Sézary syndrome and mycosis fungoides arise from distinct T-cell subsets: a biologic rationale for their distinct clinical behaviours. Blood. 2010;116(5):767–71.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Samimi S, Benoit B, Evans K, Wherry EJ, Showe L, Wysocka M, et al. Increased programmed death-1 expression on CD4+ T-cells in cutaneous T-cell lymphoma: implications for immune suppression. Arch Dermatol. 2010;146(12):1382–8.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Choi J, et al. Genomic landscape of cutaneous T-cell lymphoma. Nat Genet. 2015;47(9):1101–9.CrossRefGoogle Scholar
  17. 17.
    Wang L, Ni X, Covington KR, Yang BY, Shiu J, Zhang X, et al. Genomic profiling of Sézary syndrome identifies alterations of key T-cell signaling and differentiation genes. Nat Genet. 2015;47(12):1426–34.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    da Silva Almeida AC, Abate F, Khiabanian H, Martinez-Escala E, Guitart J, Tensen CP, et al. The mutational landscape of cutaneous T-cell lymphoma and Sézary syndrome. Nat Genet. 2015;47(12):1465–70.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Cetinozman F, et al. Differential expression of programmed death-1 (PD-1) in Sézary syndrome and mycosis fungoides. Arch Dermatol. 2012;148(12):1379–85.PubMedCrossRefGoogle Scholar
  20. 20.
    McGirt LY, Jia P, Baerenwald DA, Duszynski RJ, Dahlman KB, Zic JA, et al. Whole-genome sequencing reveals ontogenic mutations in mycosis fungoides. Blood. 2015;126(4):508–19.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Hughes CF, Newland K, McCormack C, Lade S, Prince HM. Mycosis fungoides and Sézary syndrome: current challenges in assessment, management and prognostic markers. Australas J Dermatol. 2016;57(3):182–91.PubMedCrossRefGoogle Scholar
  22. 22.
    Talpur R, Singh L, Daulat S, Liu P, Seyfer S, Trynosky T, et al. Long-term outcomes of 1,263 patients with mycosis fungoides and Sézary syndrome from 1982 to 2009. Clin Cancer Res. 2012;18(18):5051–60.PubMedCrossRefGoogle Scholar
  23. 23.
    Scarisbrick JJ, Kim YH, Whittaker SJ, Wood GS, Vermeer MH, Prince HM, et al. Prognostic factors, prognostic indices and staging in mycosis fungoides and Sézary syndrome: where are we now? Br J Dermatol. 2014;170(6):1226–36.PubMedCrossRefGoogle Scholar
  24. 24.
    Diamandidou E, Colome M, Fayad L, Duvic M, Kurzrock R. Prognostic factor analysis in mycosis fungoides/Sézary syndrome. J Am Acad Dermatol. 1999;40(6 Pt 1):914–24.PubMedCrossRefGoogle Scholar
  25. 25.
    Benner MF, Jansen PM, Vermeer MH, Willemze R. Prognostic factors in transformed mycosis fungoides: a retrospective analysis of 100 cases. Blood. 2012;119(7):1643–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Fraser-Andrews EA, Woolford AJ, Russell-Jones R, Whittaker SJ, Seed PT. Detection of a peripheral blood T-cell clone is an independent prognostic marker in mycosis fungoides. J Investig Dermatol. 2000;114(1):117–21.PubMedCrossRefGoogle Scholar
  27. 27.
    Olsen EA, Whittaker S, Kim YH, Duvic M, Prince HM, Lessin SR, 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. 2011;29(18):2598–607.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Tancrede-Bohin E, et al. Prognostic value of blood eosinophilia in primary cutaneous T-cell lymphomas. Arch Dermatol. 2004;140(9):1057–61.PubMedCrossRefGoogle Scholar
  29. 29.
    Gerami P, Rosen S, Kuzel T, Boone SL, Guitart J. Folliculotropic mycosis fungoides: an aggressive variant of cutaneous T-cell lymphoma. Arch Dermatol. 2008;144(6):738–46.PubMedCrossRefGoogle Scholar
  30. 30.
    Lehman JS, Cook-Norris RH, Weed BR, Weenig RH, Gibson LE, Weaver AL, et al. Folliculotropic mycosis fungoides: single-center study and systematic review. Arch Dermatol. 2010;146(6):607–13.PubMedCrossRefGoogle Scholar
  31. 31.
    Benton EC, Crichton S, Talpur R, Agar NS, Fields PA, Wedgeworth E, et al. A cutaneous lymphoma international prognostic index (CLIPi) for mycosis fungoides and Sézary syndrome. Eur J Cancer. 2013;49(13):2859–68.PubMedCrossRefGoogle Scholar
  32. 32.
    • Scarisbrick JJ, et al. Cutaneous lymphoma international consortium study of the outcome in advanced stages of mycosis fungoides and Sézary syndrome: effect of specific prognostic markers on survival and development of a prognostic model. J Clin Oncol. 2015;33(32):3766–73. An international retrospective study, one of the first to clearly define prognostic markers in a large number of patients using data from multiple centres globally. PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Trautinger F, Knobler R, Willemze R, Peris K, Stadler R, Laroche L, et al. EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome. Eur J Cancer. 2006;42(8):1014–30.PubMedCrossRefGoogle Scholar
  34. 34.
    Group, E.G.W, Dummer R. Primary cutaneous lymphomas: ESMO clinical recommendations for diagnosis, treatment and follow-up. [Erratum appears in Ann Oncol. 2008 May; 19(5): 1027–9]. Ann Oncol. 2007;18(Suppl 2):ii61–2.Google Scholar
  35. 35.
    Horwitz SM, Olsen EA, Duvic M, Porcu P, Kim YH. Review of the treatment of mycosis fungoides and sézary syndrome: a stage-based approach. J Natl Compr Cancer Netw. 2008;6(4):436–42.CrossRefGoogle Scholar
  36. 36.
    Olsen EA, Rook AH, Zic J, Kim Y, Porcu P, Querfeld C, 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. 2011;64(2):352–404.PubMedCrossRefGoogle Scholar
  37. 37.
    •• Quaglino P, et al. Global patterns of care in advanced stage mycosis fungoides/Sézary syndrome: a multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium. Ann Oncol. 2017;28(10):2517–25. A global and comprehensive review of the current therapeutic landscape in CTCL, highlighting the challenges in generating evidence-based guidelines in this disease. PubMedCrossRefGoogle Scholar
  38. 38.
    Nieto-Rementeria N, et al. Bexarotene activates the p53/p73 pathway in human cutaneous T-cell lymphoma. Br J Dermatol. 2009;160(3):519–26.PubMedCrossRefGoogle Scholar
  39. 39.
    Duvic M, Hymes K, Heald P, Breneman D, Martin AG, Myskowski 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. 2001;19(9):2456–71.PubMedCrossRefGoogle Scholar
  40. 40.
    Duvic M, Martin AG, Kim Y, Olsen E, Wood GS, Crowley CA, et al. Phase 2 and 3 clinical trial of oral bexarotene (Tagretin capsules) for the treatment of refectory or persistent early-stage cutaneous T-cell lymphoma. Arch Dermatol. 2001;137(5):581–93.PubMedGoogle Scholar
  41. 41.
    Olsen EA, Kim YH, Kuzel TM, Pacheco TR, Foss FM, Parker S, et al. Phase IIB multicenter trial of Vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma. J Clin Oncol. 2007;25:3109–15.PubMedCrossRefGoogle Scholar
  42. 42.
    •• Prince HM, et al. Brentuximab vedotin or physician’s choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicenter trial. Lancet. 2017;390(10094):555–66. Pivotal phase III clinical trial examining a novel agent (Brentuximab vedotin) against standard-of care therapies. PubMedCrossRefGoogle Scholar
  43. 43.
    Vakeva L, Ranki A, Hahtola S. Ten-year experience of bexarotene therapy for cutaneous T-cell lymphoma in Finland. Acta Derm Venereol. 2012;92(3):258–63.PubMedCrossRefGoogle Scholar
  44. 44.
    Sokolowska-Wojdylo M, Florek A, Zaucha JM, Chmielowska E, Giza A, Knopinska-Posluszny W, et al. Polish lymphoma research group experience with bexarotene in the treatment of cutaneous T-cell lymphoma. Am J Ther. 2016;23(3):e749–56.PubMedCrossRefGoogle Scholar
  45. 45.
    Talpur R, Ward S, Apisarnthanarax N, Breuer-McHam J, Duvic M. Optimizing bexarotene therapy for cutaneous T-cell lymphoma. J Am Acad Dermatol. 2002;47(5):672–84.PubMedCrossRefGoogle Scholar
  46. 46.
    Tsirigotis P, Pappa V, Papageorgiou S, Kapsimali V, Giannopoulou V, Kaitsa I, et al. Extracorporeal photopheresis in combination with bexarotene in the treatment of mycosis fungoides and Sézary syndrome. Br J Dermatol. 2007;156(6):1379–81.PubMedCrossRefGoogle Scholar
  47. 47.
    Straus DJ, Duvic M, Kuzel T, Horwitz S, Demierre MF, Myskowski P, et al. Results of a phase II trial of oral bexarotene (Targretin) combined with interferon alfa-2b (Intron-A) for patients with cutaneous T-cell lymphoma. Cancer. 2007;109(9):1799–803.PubMedCrossRefGoogle Scholar
  48. 48.
    Kannangara AP, Levitan D, Fleischer AB Jr. Evaluation of the efficacy of the combination of oral bexarotene and methotrexate for the treatment of early stage treatment-refractory cutaneous T-cell lymphoma. J Dermatol Treat. 2009;20(3):169–76.CrossRefGoogle Scholar
  49. 49.
    Foss S, Demierre MF, DiVenuti G. A phase-1 trial of bexarotene and denileukin diftitox in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood. 2005;106(2):454–7.PubMedCrossRefGoogle Scholar
  50. 50.
    Talpur R, Duvic M. Treatment of mycosis fungoides with denileukin diftitox and oral bexarotene. Clin Lymphoma Myeloma. 2006;6(6):488–92.PubMedCrossRefGoogle Scholar
  51. 51.
    Illidge T, Chan C, Counsell N, Morris S, Scarisbrick J, Gilson D, et al. Phase II study of gemcitabine and bexarotene (GEMBEX) in the treatment of cutaneous T-cell lymphoma. Br J Cancer. 2013;109(10):2566–73.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Talpur R, Thompson A, Gangar P, Duvic M. Pralatrexate alone or in combination with bexarotene: long-term tolerability in relapsed/refractory mycosis fungoides. Clin Lymphoma Myeloma Leuk. 2014;14(4):297–304.PubMedCrossRefGoogle Scholar
  53. 53.
    Scarisbrick JJ, Morris S, Azurdia R, Illidge T, Parry E, Graham-Brown R, et al. U.K. consensus statement on safe clinical prescribing of bexarotene for patients with cutaneous T-cell lymphoma. Br J Dermatol. 2013;168(1):192–200.PubMedCrossRefGoogle Scholar
  54. 54.
    Rupoli S, Canafoglia L, Goteri G, Leoni P, Brandozzi G, Federici I, et al. Results of a prospective phase II trial with oral low-dose bexarotene plus photo chemotherapy (PUVA) in refractory and/or relapsed patients with mycosis fungoides. Eur J Dermatol. 2016;26(1):13–20.PubMedGoogle Scholar
  55. 55.
    Suchin KR, Cassin M, Gottleib SL, Sood S, Cucchiara AJ, Vonderheid EC, et al. Increased interleukin 5 production in eosinophilic Sézary syndrome: regulation by interferon alfa and interleukin 12. J Am Acad Dermatol. 2001;44(1):28–32.PubMedCrossRefGoogle Scholar
  56. 56.
    Yoo EK, Cassin M, Lessin SR, Rook AH. Complete molecular remission during biologic response modifier therapy for Sézary syndrome is associated with enhanced helper T type 1 cytokine production and natural killer cell activity. J Am Acad Dermatol. 2001;45(2):208–16.PubMedCrossRefGoogle Scholar
  57. 57.
    Olsen EA, Bunn PA. Interferon in the treatment of cutaneous T-cell lymphoma. Hematol Oncol Clin North Am. 1995;9(5):1089–107.PubMedGoogle Scholar
  58. 58.
    Furudate S, Fujimura T, Kakizaki A, Hidaka T, Asano M, Aiba S. Tumor-associated M2 macrophages in mycosis fungoides acquire immunomodulatory function by interferon alpha and interferon gamma. J Dermatol Sci. 2016;83(3):182–9.PubMedCrossRefGoogle Scholar
  59. 59.
    Bunn PA Jr, et al. Recombinant leukocyte A interferon: an active agent in advanced cutaneous T-cell lymphomas. Ann Intern Med. 1984;101(4):484–7.PubMedCrossRefGoogle Scholar
  60. 60.
    Jumbou O, et al. Long-term follow-up in 51 patients with mycosis fungoides and Sézary syndrome treated by interferon-alfa. Br J Dermatol. 1999;140(3):427–31.PubMedCrossRefGoogle Scholar
  61. 61.
    Hughes CF, et al. Lack of durable disease control with chemotherapy for mycosis fungoides and Sézary syndrome: a comparative study of systemic therapy. Blood. 2015;125(1):71–81.PubMedCrossRefGoogle Scholar
  62. 62.
    Rook AH, Prystowsky MB, Cassin M, Boufal M, Lessin SR. Combined therapy for Sézary syndrome with extracorporeal photo chemotherapy and low-dose interferon alfa therapy. Clinical, molecular, and immunologic observations. Arch Dermatol. 1991;127(10):1535–40.PubMedCrossRefGoogle Scholar
  63. 63.
    Ferenczi K, Yawalkar N, Jones D, Kupper TS. Monitoring the decrease of circulating malignant T-cells in cutaneous T-cell lymphoma during photopheresis and interferon therapy. Arch Dermatol. 2003;139(7):909–13.PubMedCrossRefGoogle Scholar
  64. 64.
    Stadler R, Otte HG. Combination therapy of cutaneous T-cell lymphoma with interferon alpha-2a and photo chemotherapy. Recent Results Cancer Res. 1995;139:391–401.PubMedCrossRefGoogle Scholar
  65. 65.
    Kuzel TM, Roenigk HH Jr, Samuelson E, Herrmann JJ, Hurria A, Rademaker AW, et al. Effectiveness of interferon alfa-2a combined with phototherapy for mycosis fungoides and the Sézary syndrome. J Clin Oncol. 1995;13(1):257–63.PubMedCrossRefGoogle Scholar
  66. 66.
    Garcia-Vega Y, et al. Pharmacokinetic and pharmacodynamic characterization of a new formulation containing synergistic proportions of interferons alpha-2b and gamma (HeberPAG) in patients with mycosis fungoides: an open-label trial. BMC Pharmacol Toxicol. 2012;13:20.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Olsen EA. Interferon in the treatment of cutaneous T-cell lymphoma. Dermatol Ther. 2003;16(4):311–21.PubMedCrossRefGoogle Scholar
  68. 68.
    Aldebert D, et al. Eosinophilic express a functional receptor for interferon alfa: inhibitory role of interferon alfa on the release of mediators. Blood. 2017;87(6):2354–60.Google Scholar
  69. 69.
    Kurzrock R, Quesada JR, Talpaz M, Hersh EM, Reuben JM, Sherwin SA, et al. Phase I study of multiple dose intramuscularly administered recombinant gamma interferon. J Clin Oncol. 1986;4(7):1101–9.PubMedCrossRefGoogle Scholar
  70. 70.
    Kaplan EH, Rosen ST, Norris DB, Roenigk HH, Saks SR, Bunn PA. Phase II study of recombinant human interferon gamma for treatment of cutaneous T-cell lymphoma. J Natl Cancer Inst. 1990;82(3):208–12.PubMedCrossRefGoogle Scholar
  71. 71.
    Sugaya M, Tokura Y, Hamada T, Tsuboi R, Moroi Y, Nakahara T, et al. Phase II study of i.v. interferon-gamma in Japanese patients with mycosis fungoides. J Dermatol. 2014;41(1):50–6.PubMedCrossRefGoogle Scholar
  72. 72.
    Edelson R, Berger C, Gasparro F, Jegasothy B, Heald P, Wintroub B, et al. Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy. Preliminary results. N Engl J Med. 1987;316(6):297–303.PubMedCrossRefGoogle Scholar
  73. 73.
    Scarisbrick JJ, Taylor P, Holtick U, Makar Y, Douglas K, Berlin G, 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. 2008;158(4):659–78.PubMedCrossRefGoogle Scholar
  74. 74.
    Alfred A, Taylor PC, Dignan F, el-Ghariani K, Griffin J, Gennery AR, et al. The role of extracorporeal photopheresis in the management of cutaneous T-cell lymphoma, graft-versus-host disease and organ transplant rejection: a consensus statement update from the UK Photopheresis Society. Br J Hematol. 2017;177(2):287–310.CrossRefGoogle Scholar
  75. 75.
    Arulogun S, Prince HM, Gambell P, Lade S, Ryan G, Eaton E, et al. Extracorporeal photopheresis for the treatment of Sézary syndrome using a novel treatment protocol. J Am Acad Dermatol. 2008;59(4):589–95.PubMedCrossRefGoogle Scholar
  76. 76.
    Gottlieb SL, Wolfe JT, Fox FE, DeNardo BJ, Macey WH, Bromley PG, et al. Treatment of cutaneous T-cell lymphoma with extracorporeal photopheresis monotherapy and in combination with recombinant interferon alfa: a 10-year experience at a single institution. J Am Acad Dermatol. 1996;35(6):946–57.PubMedCrossRefGoogle Scholar
  77. 77.
    Wollina U, Looks A, Meyer J, Knopf B, Koch HJ, Liebold K, et al. Treatment of cutaneous T-cell lymphoma stage II with interferon-alpha-2a and extracorporeal photochemotherapy: a prospective controlled trial. Ann N Y Acad Sci. 2001;941:210–3.PubMedCrossRefGoogle Scholar
  78. 78.
    Suchin KR, Cucchiara AJ, Gottleib SL, Wolfe JT, DeNardo B, Macey WH, et al. Treatment of cutaneous T-cell lymphoma with combined immunomodulatory therapy: a 14-year experience at a single institution. Arch Dermatol. 2002;138(8):1054–60.PubMedCrossRefGoogle Scholar
  79. 79.
    Bisaccia E, Gonzalez J, Palangio M, Schwartz J, Klainer AS. Extracorporeal photochemotherapy alone or with adjuvant therapy in the treatment of cutaneous T-cell lymphoma: a 9-year retrospective study at a single institution. J Am Acad Dermatol. 2000;43(2 Pt 1):263–71.PubMedCrossRefGoogle Scholar
  80. 80.
    Shen S, O’Brien T, Yap LM, Prince HM, McCormack CJ. The use of methotrexate in dermatology: a review. Australas J Dermatol. 2012;53(1):1–18.PubMedCrossRefGoogle Scholar
  81. 81.
    Zackheim HS, Kashani-Sabet M, McMillan A. Low-dose methotrexate to treat mycosis fungoides: a retrospective study in 69 patients. J Am Acad Dermatol. 2003;49(5):873–8.PubMedCrossRefGoogle Scholar
  82. 82.
    Chen R, Hou J, Newman E, Kim Y, Donohue C, Liu X, et al. CD30 downregulation, MMAE resistance, and MDR1 upregulation are all associated with resistance to brentuximab vedotin. Mol Cancer Ther. 2015;14(6):1376–84.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Prince HM. CD30 as a target for the treatment of cutaneous T-cell lymphoma. J Clin Oncol. 2015;33(32):3691–6.PubMedCrossRefGoogle Scholar
  84. 84.
    Kim YH, Tavallaee M, Sundram U, Salva KA, Wood GS, Li S, et al. Phase II investigator-initiated study of brentuximab vedotin in mycosis fungoides and Sézary syndrome with variable CD30 expression level: a multi-institution collaborative project. J Clin Oncol. 2015;33(32):3750–8.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Duvic M, Tetzlaff MT, Gangar P, Clos AL, Sui D, Talpur R. Results of phase II trial of brentuximab vedotin for CD30+ cutaneous T-cell lymphoma and lymphomatoid papulosis. J Clin Oncol. 2015;33(32):3759–65.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Ogura M, Ishida T, Hatake K, Taniwaki M, Ando K, Tobinai K, et al. Multicenter phase II study of mogamulizumab (KW-0761), a defucosylated anti-cc chemokine receptor 4 antibody, in patients with relapsed peripheral T-cell lymphoma and cutaneous T-cell lymphoma. J Clin Oncol. 2014;32(11):1157–63.PubMedCrossRefGoogle Scholar
  87. 87.
    •• Kim KY, et al. Anti-CCR4 monoclonal antibody, mogamulizumab, demonstrates significant improvement in PFS compared to vorinostat in patients with previously treated cutaneous T-cell lymphoma (CTCL): results from the Phase III MAVORIC Study. In Press, 2017. Being presented at ASH 59th Annual Meeting and Exposition, December 9–12 2017, Atlanta. Pivotal phase III clinical trial examining a novel agent (Mogamulizumab) against another novel, widely used agent. Google Scholar
  88. 88.
    Duvic M, Pinter-Brown LC, Foss FM, Sokol L, Jorgensen JL, Challagundla P, et al. Phase 1/2 study of mogamulizumab, a defucosylated anti-CCR4 antibody, in previously treated patients with cutaneous T-cell lymphoma. Blood. 2015;125(12):1883–9.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Ishida T, Ito A, Sato F, Kusumoto S, Iida S, Inagaki H, et al. Stevens-Johnson syndrome associated with mogamulizumab treatment of adult T-cell leukemia/lymphoma. Cancer Sci. 2013;104(5):647–50.PubMedCrossRefGoogle Scholar
  90. 90.
    Honda T, Hishizawa M, Kataoka TR, Ohmori K, Takaori-Kondo A, Miyachi Y, et al. Stevens-Johnson syndrome associated with Mogamulizumab-induced deficiency of regulatory T-cells in an adult T-cell leukaemia patient. Acta Derm Venereol. 2015;95(5):606–7.PubMedCrossRefGoogle Scholar
  91. 91.
    Lundin J, Hagberg H, Repp R, Cavallin-Ståhl E, Fredén S, Juliusson G, et al. Phase 2 study of alemtuzumab (anti-CD52 monoclonal antibody) in patients with advanced mycosis fungoides/Sézary syndrome. Blood. 2003;101(11):4267–72.PubMedCrossRefGoogle Scholar
  92. 92.
    de Masson A, Guitera P, Brice P, Moulonguet I, Mouly F, Bouaziz JD, et al. Long-term efficacy and safety of alemtuzumab in advanced primary cutaneous T-cell lymphomas. Br J Dermatol. 2014;170(3):720–4.PubMedCrossRefGoogle Scholar
  93. 93.
    Kennedy GA, Seymour JF, Wolf M, Januszewicz H, Davison J, McCormack C, et al. Treatment of patients with advanced mycosis fungoides and Sézary syndrome with alemtuzumab. Eur J Hematol. 2003;71(4):250–6.CrossRefGoogle Scholar
  94. 94.
    Querfeld C, Mehta N, Rosen ST, Guitart J, Rademaker A, Gerami P, et al. Alemtuzumab for relapsed and refractory erythrodermic cutaneous T-cell lymphoma: a single institution experience from the Robert H. Lurie Comprehensive Cancer Centre. Leuk Lymphoma. 2009;50(12):1969–76.PubMedCrossRefGoogle Scholar
  95. 95.
    Zinzani PL, et al. Preliminary observations of a phase II study of reduced-dose alemtuzumab treatment in patients with pretreated T-cell lymphoma. Hematologica. 2005;90(5):702–3.Google Scholar
  96. 96.
    Bernengo MG, Quaglino P, Comessatti A, Ortoncelli M, Novelli M, Lisa F, et al. Low-dose intermittent alemtuzumab in the treatment of Sézary syndrome: clinical and immunologic findings in 14 patients. Haematologica. 2007;92(6):784–94.PubMedCrossRefGoogle Scholar
  97. 97.
    Alinari L, Geskin L, Grady T, Baiocchi RA, Bechtel MA, Porcu P. Subcutaneous alemtuzumab for Sézary syndrome in the very elderly. Leuk Res. 2008;32(8):1299–303.PubMedCrossRefGoogle Scholar
  98. 98.
    Clark RA, Watanabe R, Teague JE, Schlapbach C, Tawa MC, Adams N, et al. Skin effector memory T-cells do not recirculate and provide immune protection in alemtuzumab-treated CTCL patients. Sci Transl Med. 2012;4(117):117ra7.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Duvic M. Choosing a systemic treatment for advanced stage cutaneous T-cell lymphoma: mycosis fungoides and Sézary syndrome. Haemtology. 2015;2015:529–44.CrossRefGoogle Scholar
  100. 100.
    Duvic M. Histone deacetylase inhibitors for cutaneous T-cell lymphoma. Dermatol Clin. 2015;33(4):757–64.PubMedCrossRefGoogle Scholar
  101. 101.
    Johnstone RW, Licht JD. Histone deacetylase inhibitors in cancer therapy: is transcription the primary target? Cancer Cell. 2003;4(1):13–8.PubMedCrossRefGoogle Scholar
  102. 102.
    Duvic M, Vu J. Vorinostat: a new oral histone deacetylase inhibitor approved for cutaneous T-cell lymphoma. Expert Opin Investig Drugs. 2007;16(7):1111–20.PubMedCrossRefGoogle Scholar
  103. 103.
    Piekarz RL, Frye R, Turner M, Wright JJ, Allen SL, Kirschbaum MH, 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. 2009;27(32):5410–7.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Whittaker SJ, Demierre MF, Kim EJ, Rook AH, Lerner A, Duvic M, et al. Final results from a multicenter, international, pivotal study of romidepsin in refractory cutaneous T-cell lymphoma. J Clin Oncol. 2010;28(29):4485–91.PubMedCrossRefGoogle Scholar
  105. 105.
    Bates SE, Eisch R, Ling A, Rosing D, Turner M, Pittaluga S, et al. Romidepsin in peripheral and cutaneous T-cell lymphoma: mechanistic implications from clinical and correlative data. Br J Haematol. 2015;170(1):96–109.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    van der Weyden C, Dickinson M, Bates SE, Prince HM. Use of romidepsin for the treatment of mycosis fungoides and Sézary syndrome—role of romidepsin in the current therapeutic landscape and implications for future practice. Expert Opin Orphan Drugs. 2015;3(10):1231–9.CrossRefGoogle Scholar
  107. 107.
    Duvic M, Geskin L, Prince HM. Duration of responses in cutaneous T-cell lymphoma patients treated with denileukin diftitox: results from 3 phase III studies. Clin Lymphoma Myeloma Leuk. 2013;13(4):377–84.PubMedCrossRefGoogle Scholar
  108. 108.
    Prince HM, Duvic M, Martin A, Sterry W, Assaf C, Sun Y, et al. Phase III placebo-controlled trial of denileukin diftitox for patients with cutaneous T-cell lymphoma. J Clin Oncol. 2010;28(11):1870–7.PubMedCrossRefGoogle Scholar
  109. 109.
    Duvic M, Martin AG, Olsen EA, Fivenson DP, Prince HM. Efficacy and safety of denileukin diftitox pretreatment in patients with relapsed cutaneous T-cell lymphoma. Leuk Lymphoma. 2013;54(3):514–9.PubMedCrossRefGoogle Scholar
  110. 110.
    Wollina U, Dummer R, Brockmeyer NH, Konrad H, Busch JO, Kaatz M, et al. Multicenter study of pegylated liposomal doxorubicin in patients with cutaneous T-cell lymphoma. Cancer. 2003;98(5):993–1001.PubMedCrossRefGoogle Scholar
  111. 111.
    Zinzani PL, Bonthapally V, Huebner D, Lutes R, Chi A, Pileri S. Panoptic clinical review of the current and future treatment of relapsed/refractory T-cell lymphomas: cutaneous T-cell lymphomas. Crit Rev Oncol Hematol. 2016;99:228–40.PubMedCrossRefGoogle Scholar
  112. 112.
    Damaj G, Gressin R, Bouabdallah K, Cartron G, Choufi B, Gyan E, et al. Results from a prospective, open-label, phase II trial of bendamustine in refractory or relapsed T-cell lymphomas: the BENTLY trial. J Clin Oncol. 2013;31(1):104–10.PubMedCrossRefGoogle Scholar
  113. 113.
    Zaja F, Baldini L, Ferreri AJM, Luminari S, Grossi A, Salvi F, et al. Bendamustine salvage therapy for T-cell neoplasms. Ann Haematol. 2013;92(9):1249–54.CrossRefGoogle Scholar
  114. 114.
    Coors EA, von den Driesch P. Treatment of erythrodermic cutaneous T-cell lymphoma with intermittent chlorambucil and floortolone treatment. Br J Dermatol. 2000;143:127–31.PubMedCrossRefGoogle Scholar
  115. 115.
    Scarisbrick JJ, Child FJ, Clift A, Sabroe R, Whittaker SJ, Spittle M, et al. A trial of fludarabine and cyclophosphamide combination chemotherapy in the treatment of advanced refractory primary cutaneous T-cell lymphoma. Br J Dermatol. 2001;144(5):1010–5.PubMedCrossRefGoogle Scholar
  116. 116.
    Akpek G, Koh HK, Bogen S, O'Hara C, Foss FM. Chemotherapy with etoposide, vincristine, doxorubicin, bolus cyclophosphamide, and oral prednisone in patients with refractory cutaneous T-cell lymphoma. Cancer. 1999;86(7):1368–76.PubMedCrossRefGoogle Scholar
  117. 117.
    Molin L, Thomsen K, Volden G, Groth O, Hellbe L, Holst R, et al. Combination chemotherapy in the tumour stage of mycosis fungoides with cyclophosphamide, vincristine, vp-16, adriamycin and prednisolone (cop, chop, capo): a report from the Scandinavian mycosis fungoides study group. Acta Derm Venereol. 1980;60(6):542–4.PubMedGoogle Scholar
  118. 118.
    O’Connor OA, Amengual J, Colbourn D, Deng C, Sawas A. Pralatrexate: a comprehensive update on pharmacology, clinical activity and strategies to optimize use. Leuk Lymphoma. 2017;58(11):2548–57.PubMedCrossRefGoogle Scholar
  119. 119.
    Wang ES, O'Connor O, She Y, Zelenetz AD, Sirotnak FM, Moore MAS. Activity of a novel anti-folate (PDX, 10-propargyl 10-deazaaminopterin) against human lymphoma is superior to methotrexate and correlates with tutor RFC-1 gene expression. Leuk Lymphoma. 2003;44(6):1027–35.PubMedCrossRefGoogle Scholar
  120. 120.
    O’Connor OA, et al. Pralatrexate in patients with relapsed or refractory peripheral T-cell lymphoma: results from the pivotal PROPEL study. J Clin Oncol. 2011;29(9):1182–9.PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Foss F, Horwitz SM, Coiffier B, Bartlett N, Popplewell L, Pro B, et al. Pralatrexate is an effective treatment for relapsed or refractory transformed mycosis fungoides: a subgroup efficacy analysis from the PRPOEL study. Clin Lymphoma Myeloma Leuk. 2012;12(4):238–43.PubMedCrossRefGoogle Scholar
  122. 122.
    Horwitz SM, Kim YH, Foss F, Zain JM, Myskowski PL, Lechowicz MJ, et al. Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood. 2012;119(18):4115–22.PubMedCrossRefGoogle Scholar
  123. 123.
    Querfeld C, Rosen ST, Guitart J, Duvic M, Kim YH, Dusza SW, et al. Results of an open-label multicenter phase 2 trial of lenalidomide monotherapy in refractory mycosis fungoides and Sézary syndrome. Blood. 2014;123(8):1159–66.PubMedCrossRefGoogle Scholar
  124. 124.
    Battistella M, Janin A, Jean-Louis F, Collomb C, Leboeuf C, Sicard H, et al. KIR3DL2 (CD158k) is a potential therapeutic target in primary cutaneous anapaestic large-cell lymphoma. Br J Dermatol. 2016;175(2):325–33.PubMedCrossRefGoogle Scholar
  125. 125.
    Bar-Sela G, Bergman R. Complete regression of mycosis fungoides after ipilimumab therapy for advanced melanoma. J Am Acad Dermatol Case Rep. 2015;1(2):99–100.Google Scholar
  126. 126.
    Lesokhin AM, Ansell SM, Armand P, Scott EC, Halwani A, Gutierrez M, et al. Nivolimumab in patients with relapsed or refractory haematology malignancy: preliminary results of a phase Ib study. J Clin Oncol. 2016;34(23):2698–704.PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Duvic M, Dummer R, Becker JC, Poulalhon N, Ortiz Romero P, Grazia Bernengo M, et al. Panobinostat activity in both bexarotene-exposed and -naive patients with refractory cutaneous T-cell lymphoma: results of a phase II trial. Eur J Cancer. 2013;49(2):386–94.PubMedCrossRefGoogle Scholar
  128. 128.
    Child F, Ortiz-Romero PL, Alvarez R, Bagot M, Stadler R, Weichenthal M, et al. Phase II multicentre trial of oral quisinostat, a histone deacetylase inhibitor, in patients with previously treated stage IB-IVA mycosis fungoides/Sézary syndrome. Br J Dermatol. 2016;175(1):80–8.PubMedCrossRefGoogle Scholar
  129. 129.
    Frankel AE, Woo JH, Ahn C, Foss FM, Duvic M, Neville PH, et al. Resimmune, an anti-CD3epsilon recombinant immunotoxin, induces durable remissions in patients with cutaneous T-cell lymphoma. Haematologica. 2015;100(6):794–800.PubMedPubMedCentralCrossRefGoogle Scholar
  130. 130.
    Heider U, Rademacher J, Lamottke B, Mieth M, Moebs M, von Metzler I, et al. Synergistic interaction of the histone deacetylase inhibitor SAHA with the proteasome inhibitor bortezomib in cutaneous T-cell lymphoma. Eur J Haematol. 2009;82(6):440–9.PubMedCrossRefGoogle Scholar
  131. 131.
    Mpakou V, et al. Apoptosis induction and gene expression profile alterations of cutaneous T-cell lymphoma cells following their exposure to bortezomib and methotrexate. PLoS One [Electron Resour]. 2017;12(1):e0170186.CrossRefGoogle Scholar
  132. 132.
    Zinzani PL, Musuraca G, Tani M, Stefoni V, Marchi E, Fina M, et al. Phase II trial of proteasome inhibitor bortezomib in patients with relapsed or refractory cutaneous T-cell lymphoma. J Clin Oncol. 2007;25(27):4293–7.PubMedCrossRefGoogle Scholar
  133. 133.
    Ungewickell A, Bhaduri A, Rios E, Reuter J, Lee CS, Mah A, et al. Genomic analysis of mycosis fungoides and Sézary syndrome identifies recurrent alterations in TNFR2. Nat Genet. 2015;47(9):1056–60.PubMedCrossRefGoogle Scholar
  134. 134.
    Horwitz SM, et al. Duvelisib (IPI-145), a phosphoinositide-3-kinase-inhibitor, shows activity in patients with relapsed/refractory T-cell lymphoma. Blood. 2014;124(21):803. Presented at ASH 56th Annual Meeting and Exposition, December 6-9 2014, San FranciscoGoogle Scholar
  135. 135.
    Marzec M, Liu X, Kasprzycka M, Witkiewicz A, Raghunath PN, el-Salem M, et al. Il-2 and IL-5-induced activation of the rapamycin-sensitive mTORC1 pathway in malignant CD4+ T lymphocytes. Blood. 2008;111(4):2181–9.PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Blachly JS, Baiocchi RA. Targeting PI3-kinase (PI3K), AKT and mTOR axis in lymphoma. Br J Haematol. 2014;167(1):19–32.PubMedCrossRefGoogle Scholar
  137. 137.
    Witzig TE, Reeder C, Han JJ, LaPlant B, Stenson M, Tun HW, et al. The mTORC1 inhibitor everolimus has anti tumour activity in vitro an dproduces tutor responses in patients with relapsed T-cell lymphoma. Blood. 2015;126(3):328–35.PubMedPubMedCentralCrossRefGoogle Scholar
  138. 138.
    Marzec M, et al. Simulataneous inhibition of mTOR-containing complex 1 (mTORC1) and MNK induces apoptosis of cutaneous T-cell lymphoma (CTCL) cells. PLoS One [Electron Resour]. 2011;6(9):e24849.CrossRefGoogle Scholar
  139. 139.
    Sorm F, et al. 5-Azacytidine, a new, highly effective cancerostatic. Experientia. 1964;20(4):202–3.PubMedCrossRefGoogle Scholar
  140. 140.
    Delarue R, et al. Treatment with hypomethylating agent 5-azacytidine induces sustained response in angioimmunoblastic T cell lymphomas. Blood. 2016;128:4164.Google Scholar
  141. 141.
    Cheminant M, Bruneau J, Kosmider O, Lefrere F, Delarue R, Gaulard P, et al. Efficacy of 5-azacytidine in a TET2 mutated angioimmunoblastic T cell lymphoma. Br J Haematol. 2015;168(6):913–6.PubMedCrossRefGoogle Scholar
  142. 142.
    Saillard C, el Cheikh J, Granata A, Coso D, Schiano JM, Bouabdallah R, et al. Histone deacetylase inhibitor abexinostat (S78454/PCI-24781) as a successful approach in a case of refractory peripheral angio-immunoblastic T-cell lymphoma, as a bridge to reduced intensity conditioning haplo-identical allogenic stem cell transplant. Leuk Lymphoma. 2016;57(3):714–6.PubMedCrossRefGoogle Scholar
  143. 143.
    Kiel MJ, Sahasrabuddhe AA, Rolland DCM, Velusamy T, Chung F, Schaller M, et al. Genomic analyses reveal recurrent mutations in epigenetic modifiers and the JAK-STAT pathway in Sézary syndrome. Nat Commun. 2015;6:8470.PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Jones CL, Mary Wain E, Chu CC, Tosi I, Foster R, McKenzie RCT, et al. Downregulation of Fas gene expression in Sézary syndrome is associated with promoter hypermethylation. J Investig Dermatol. 2010;130(4):1116–25.PubMedCrossRefGoogle Scholar
  145. 145.
    Navas IC, Ortiz-Romero PL, Villuendas R, Martínez P, García C, Gómez E, et al. p16(INK4a) gene alterations are frequent in lesions of mycosis fungoides. Am J Pathol. 2000;156(5):1565–72.PubMedPubMedCentralCrossRefGoogle Scholar
  146. 146.
    van Doorn R, Slieker RC, Boonk SE, Zoutman WH, Goeman JJ, Bagot M, et al. Epigenomic analysis of Sézary syndrome defines patterns of aberrant DNA methylation and identifies diagnostic markers. J Investig Dermatol. 2016;136(9):1876–84.PubMedCrossRefGoogle Scholar
  147. 147.
    Ferrara G, Pancione M, Votino C, Quaglino P, Tomasini C, Santucci M, et al. A specific DNA methylation profile correlates with a high risk of disease progression in stage I classical (Alibert-Bazin type) mycosis fungoides. Br J Dermatol. 2014;170(6):1266–75.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Louise Photiou
    • 1
  • Carrie van der Weyden
    • 1
  • Christopher McCormack
    • 1
  • H. Miles Prince
    • 1
  1. 1.Peter MacCallum Cancer CentreMelbourneAustralia

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