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Personalized Treatment in Cutaneous T-Cell Lymphoma (CTCL)

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Personalized Treatment Options in Dermatology

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Abstract

Tumor therapy more and more focuses on individualized therapeutic regimens, as they allow for a maximum of efficacy in a single patient while simultaneously minimizing the risk of adverse events. Cutaneous T-cell lymphoma (CTCL) is especially suited for the development of such individualized therapeutic approaches due to its typical characteristics.

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References

  1. Abbott RA, Whittaker SJ, Morris SL, Russell-Jones R, Hung T, Bashir SJ, Scarisbrick JJ. Bexarotene therapy for mycosis fungoides and Sezary syndrome. Br J Dermatol. 2009;160:1299–307.

    Article  CAS  PubMed  Google Scholar 

  2. Baraldi S, Hepgul N, Mondelli V, Pariante CM. Symptomatic treatment of interferon-alpha-induced depression in hepatitis C: a systematic review. J Clin Psychopharmacol. 2012;32:531–43.

    Article  CAS  PubMed  Google Scholar 

  3. Bradford PT, Devesa SS, Anderson WF, Toro JR. Cutaneous lymphoma incidence patterns in the United States: a population-based study of 3884 cases. Blood. 2009;113:5064–73.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012;366:2455–65.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Braun FK, Al-Yacoub N, Plotz M, Mobs M, Sterry W, Eberle J. Nonsteroidal anti-inflammatory drugs induce apoptosis in cutaneous T-cell lymphoma cells and enhance their sensitivity for TNF-related apoptosis-inducing ligand. J Invest Dermatol. 2012;132:429–39.

    Article  CAS  PubMed  Google Scholar 

  6. Brechmann M, Mock T, Nickles D, Kiessling M, Weit N, Breuer R, Muller W, Wabnitz G, Frey F, Nicolay JP, et al. A PP4 holoenzyme balances physiological and oncogenic nuclear factor-kappa B signaling in T lymphocytes. Immunity. 2012;37:697–708.

    Article  CAS  PubMed  Google Scholar 

  7. Bunn Jr PA, Lamberg SI. Report of the committee on staging and classification of cutaneous T-cell lymphomas. Cancer Treat Rep. 1979;63:725–8.

    PubMed  Google Scholar 

  8. Campbell JJ, Haraldsen G, Pan J, Rottman J, Qin S, Ponath P, Andrew DP, Warnke R, Ruffing N, Kassam N, et al. The chemokine receptor CCR4 in vascular recognition by cutaneous but not intestinal memory T cells. Nature. 1999;400:776–80.

    Article  CAS  PubMed  Google Scholar 

  9. Cetinozman F, Jansen PM, Willemze R. Expression of programmed death-1 in primary cutaneous CD4-positive small/medium-sized pleomorphic T-cell lymphoma, cutaneous pseudo-T-cell lymphoma, and other types of cutaneous T-cell lymphoma. Am J Surg Pathol. 2012;36:109–16.

    Article  PubMed  Google Scholar 

  10. Chang DK, Sui J, Geng S, Muvaffak A, Bai M, Fuhlbrigge RC, Lo A, Yammanuru A, Hubbard L, Sheehan J, et al. Humanization of an anti-CCR4 antibody that kills cutaneous T-cell lymphoma cells and abrogates suppression by T-regulatory cells. Mol Cancer Ther. 2012;11:2451–61.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Demierre MF, Gan S, Jones J, Miller DR. Significant impact of cutaneous T-cell lymphoma on patients’ quality of life: results of a 2005 National Cutaneous Lymphoma Foundation Survey. Cancer. 2006;107:2504–11.

    Article  PubMed  Google Scholar 

  12. Demierre MF, Taverna J. Mirtazapine and gabapentin for reducing pruritus in cutaneous T-cell lymphoma. J Am Acad Dermatol. 2006;55:543–4.

    Article  PubMed  Google Scholar 

  13. Ferenczi K, Fuhlbrigge RC, Pinkus J, Pinkus GS, Kupper TS. Increased CCR4 expression in cutaneous T cell lymphoma. J Invest Dermatol. 2002;119:1405–10.

    Article  CAS  PubMed  Google Scholar 

  14. Gniadecki R, Assaf C, Bagot M, Dummer R, Duvic M, Knobler R, Ranki A, Schwandt P, Whittaker S. The optimal use of bexarotene in cutaneous T-cell lymphoma. Br J Dermatol. 2007;157:433–40.

    Article  CAS  PubMed  Google Scholar 

  15. Gupta MA, Guptat AK. The use of antidepressant drugs in dermatology. J Eur Acad Dermatol Venereol. 2001;15:512–8.

    Article  CAS  PubMed  Google Scholar 

  16. Han T, Abdel-Motal UM, Chang DK, Sui J, Muvaffak A, Campbell J, Zhu Q, Kupper TS, Marasco WA. Human anti-CCR4 minibody gene transfer for the treatment of cutaneous T-cell lymphoma. PLoS One. 2012;7:e44455.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57–70.

    Article  CAS  PubMed  Google Scholar 

  18. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.

    Article  CAS  PubMed  Google Scholar 

  19. Heid JB, Schmidt A, Oberle N, Goerdt S, Krammer PH, Suri-Payer E, Klemke CD. FOXP3+CD25- tumor cells with regulatory function in Sezary syndrome. J Invest Dermatol. 2009;129:2875–85.

    Article  CAS  PubMed  Google Scholar 

  20. Kantekure K, Yang Y, Raghunath P, Schaffer A, Woetmann A, Zhang Q, Odum N, Wasik M. Expression patterns of the immunosuppressive proteins PD-1/CD279 and PD-L1/CD274 at different stages of cutaneous T-cell lymphoma/mycosis fungoides. Am J Dermatopathol. 2012;34:126–8.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Kiessling MK, Klemke CD, Kaminski MM, Galani IE, Krammer PH, Gulow K. Inhibition of constitutively activated nuclear factor-kappaB induces reactive oxygen species- and iron-dependent cell death in cutaneous T-cell lymphoma. Cancer Res. 2009;69:2365–74.

    Article  CAS  PubMed  Google Scholar 

  22. Kiessling MK, Oberholzer PA, Mondal C, Karpova MB, Zipser MC, Lin WM, Girardi M, Macconaill LE, Kehoe SM, Hatton C, et al. High-throughput mutation profiling of CTCL samples reveals KRAS and NRAS mutations sensitizing tumors toward inhibition of the RAS/RAF/MEK signaling cascade. Blood. 2011;117:2433–40.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Kim YH, Willemze R, Pimpinelli N, Whittaker S, Olsen EA, Ranki A, Dummer R, Hoppe RT. TNM classification system for primary cutaneous lymphomas other than 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. 2007;110:479–84.

    Article  CAS  PubMed  Google Scholar 

  24. Klemke CD, Brenner D, Weiss EM, Schmidt M, Leverkus M, Gulow K, Krammer PH. Lack of T-cell receptor-induced signaling is crucial for CD95 ligand up-regulation and protects cutaneous T-cell lymphoma cells from activation-induced cell death. Cancer Res. 2009;69:4175–83.

    Article  CAS  PubMed  Google Scholar 

  25. Klemke CD, Fritzsching B, Franz B, Kleinmann EV, Oberle N, Poenitz N, Sykora J, Banham AH, Roncador G, Kuhn A, et al. Paucity of FOXP3+ cells in skin and peripheral blood distinguishes Sezary syndrome from other cutaneous T-cell lymphomas. Leukemia. 2006;20:1123–9.

    Article  CAS  PubMed  Google Scholar 

  26. Kopp KL, Ralfkiaer U, Gjerdrum LM, Helvad R, Pedersen IH, Litman T, Jonson L, Hagedorn PH, Krejsgaard T, Gniadecki R, et al. STAT5-mediated expression of oncogenic miR-155 in cutaneous T-cell lymphoma. Cell Cycle. 2013;12:1939–47.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Krejsgaard T, Gjerdrum LM, Ralfkiaer E, Lauenborg B, Eriksen KW, Mathiesen AM, Bovin LF, Gniadecki R, Geisler C, Ryder LP, et al. Malignant Tregs express low molecular splice forms of FOXP3 in Sezary syndrome. Leukemia. 2008;22:2230–9.

    Article  CAS  PubMed  Google Scholar 

  28. Krejsgaard T, Odum N, Geisler C, Wasik MA, Woetmann A. Regulatory T cells and immunodeficiency in mycosis fungoides and Sezary syndrome. Leukemia. 2012;26:424–32.

    Article  CAS  PubMed  Google Scholar 

  29. Mao X, Orchard G, Lillington DM, Child FJ, Vonderheid EC, Nowell PC, Bagot M, Bensussan A, Russell-Jones R, Young BD, et al. BCL2 and JUNB abnormalities in primary cutaneous lymphomas. Br J Dermatol. 2004;151:546–56.

    Article  CAS  PubMed  Google Scholar 

  30. Oki Y, Younes A. Brentuximab vedotin in systemic T-cell lymphoma. Expert Opin Biol Ther. 2012;12:623–32.

    Article  CAS  PubMed  Google Scholar 

  31. Olsen E, Vonderheid E, Pimpinelli N, Willemze R, Kim Y, Knobler R, Zackheim H, Duvic M, Estrach T, Lamberg S, 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. 2007;110:1713–22.

    Article  CAS  PubMed  Google Scholar 

  32. Rabenhorst A, Schlaak M, Heukamp LC, Forster A, Theurich S, von Bergwelt-Baildon M, Buttner R, Kurschat P, Mauch C, Roers A, et al. Mast cells play a protumorigenic role in primary cutaneous lymphoma. Blood. 2012;120:2042–54.

    Article  CAS  PubMed  Google Scholar 

  33. Reinhold U, Pawelec G, Fratila A, Leippold S, Bauer R, Kreysel HW. Phenotypic and functional characterization of tumor infiltrating lymphocytes in mycosis fungoides: continuous growth of CD4+ CD45R+ T-cell clones with suppressor-inducer activity. J Invest Dermatol. 1990;94:304–9.

    Article  CAS  PubMed  Google Scholar 

  34. Rothe A, Sasse S, Goergen H, Eichenauer DA, Lohri A, Jager U, Bangard C, Boll B, von Bergwelt Baildon M, Theurich S, et al. Brentuximab vedotin for relapsed or refractory CD30+ hematologic malignancies: the German Hodgkin Study Group experience. Blood. 2012;120:1470–2.

    Article  CAS  PubMed  Google Scholar 

  35. Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol. 1995;155:1151–64.

    CAS  PubMed  Google Scholar 

  36. Sors A, Jean-Louis F, Pellet C, Laroche L, Dubertret L, Courtois G, Bachelez H, Michel L. Down-regulating constitutive activation of the NF-kappaB canonical pathway overcomes the resistance of cutaneous T-cell lymphoma to apoptosis. Blood. 2006;107:2354–63.

    Article  CAS  PubMed  Google Scholar 

  37. Stadler R, Assaf C, Klemke CD, Nashan D, Weichenthal M, Dummer R, Sterry W. Brief S2k guidelines - cutaneous lymphomas. J Dtsch Dermatol Ges. 2013;11(Suppl) 3:19–28; 20–30.

    Google Scholar 

  38. Steininger A, Mobs M, Ullmann R, Kochert K, Kreher S, Lamprecht B, Anagnostopoulos I, Hummel M, Richter J, Beyer M, et al. Genomic loss of the putative tumor suppressor gene E2A in human lymphoma. J Exp Med. 2011;208:1585–93.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Talpur R, Ward S, Apisarnthanarax N, Breuer-Mcham J, Duvic M. Optimizing bexarotene therapy for cutaneous T-cell lymphoma. J Am Acad Dermatol. 2002;47:672–84.

    Article  PubMed  Google Scholar 

  40. Theurich S, Malcher J, Wennhold K, Shimabukuro-Vornhagen A, Chemnitz J, Holtick U, Krause A, Kobe C, Kahraman D, Engert A, et al. Brentuximab vedotin combined with donor lymphocyte infusions for early relapse of Hodgkin lymphoma after allogeneic stem-cell transplantation induces tumor-specific immunity and sustained clinical remission. J Clin Oncol. 2013;31:e59–63.

    Article  PubMed  Google Scholar 

  41. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366:2443–54.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. van der Fits L, Out-Luiting JJ, van Leeuwen MA, Samsom JN, Willemze R, Tensen CP, Vermeer MH. Autocrine IL-21 stimulation is involved in the maintenance of constitutive STAT3 activation in Sezary syndrome. J Invest Dermatol. 2012;132:440–7.

    Article  PubMed  Google Scholar 

  43. van der Fits L, van Kester MS, Qin Y, Out-Luiting JJ, Smit F, Zoutman WH, Willemze R, Tensen CP, Vermeer MH. MicroRNA-21 expression in CD4+ T cells is regulated by STAT3 and is pathologically involved in Sezary syndrome. J Invest Dermatol. 2011;131:762–8.

    Article  PubMed  Google Scholar 

  44. Weng WK, Armstrong R, Arai S, Desmarais C, Hoppe R, Kim YH. Minimal residual disease monitoring with high-throughput sequencing of T cell receptors in cutaneous T cell lymphoma. Sci Transl Med. 2013;5:214ra171.

    Article  PubMed  Google Scholar 

  45. Willemze R, Jaffe ES, Burg G, Cerroni L, Berti E, Swerdlow SH, Ralfkiaer E, Chimenti S, Diaz-Perez JL, Duncan LM, et al. WHO-EORTC classification for cutaneous lymphomas. Blood. 2005;105:3768–85.

    Article  CAS  PubMed  Google Scholar 

  46. Willemze R, Kerl H, Sterry W, Berti E, Cerroni L, Chimenti S, Diaz-Perez JL, Geerts ML, Goos M, Knobler R, 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. 1997;90:354–71.

    CAS  PubMed  Google Scholar 

  47. Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Ramchandren R, Bartlett NL, Cheson BD, de Vos S, et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol. 2012;30:2183–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Younes A, Yasothan U, Kirkpatrick P. Brentuximab vedotin. Nat Rev Drug Discov. 2012;11:19–20.

    Article  CAS  PubMed  Google Scholar 

  49. Zhang C, Li B, Zhang X, Hazarika P, Aggarwal BB, Duvic M. Curcumin selectively induces apoptosis in cutaneous T-cell lymphoma cell lines and patients’ PBMCs: potential role for STAT-3 and NF-kappaB signaling. J Invest Dermatol. 2010;130:2110–9.

    Article  CAS  PubMed  Google Scholar 

  50. Zuo T, Liu R, Zhang H, Chang X, Liu Y, Wang L, Zheng P. FOXP3 is a novel transcriptional repressor for the breast cancer oncogene SKP2. J Clin Invest. 2007;117:3765–73.

    PubMed Central  CAS  PubMed  Google Scholar 

  51. Zuo T, Wang L, Morrison C, Chang X, Zhang H, Li W, Liu Y, Wang Y, Liu X, Chan MW, et al. FOXP3 is an X-linked breast cancer suppressor gene and an important repressor of the HER-2/ErbB2 oncogene. Cell. 2007;129:1275–86.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin Mannheim, Mannheim, 68167, Germany

    Jan P. Nicolay MD, MSc & Claus-Detlev Klemke MD

Authors
  1. Jan P. Nicolay MD, MSc
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  2. Claus-Detlev Klemke MD
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Correspondence to Jan P. Nicolay MD, MSc .

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Editors and Affiliations

  1. Department of Dermatology and Allergy, Center of Translational Medicine, University of Bonn, Bonn, Germany

    Thomas Bieber

  2. St. John's Institute of Dermatology, London, United Kingdom

    Frank Nestle

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Nicolay, J.P., Klemke, CD. (2015). Personalized Treatment in Cutaneous T-Cell Lymphoma (CTCL). In: Bieber, T., Nestle, F. (eds) Personalized Treatment Options in Dermatology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-45840-2_4

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  • DOI: https://doi.org/10.1007/978-3-662-45840-2_4

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