Skip to main content
SpringerLink
Log in

Immunotherapy for Cutaneous T-Cell Lymphoma

  • Chapter
  • First Online:
T-Cell Lymphomas

Part of the book series: Contemporary Hematology ((CH))

  • 1262 Accesses

Abstract

The cutaneous T-cell lymphomas have been shown to be associated with dysregulation of effector T-cell activity, making them an attractive target for immune activating therapies. Interferons and extracorporeal photopheresis-based therapeutic approaches have been shown to induce clinical responses of significant duration in selected patients. Similarly, activity has been demonstrated with cytokine-based therapies, including interleukin-2, interleukin-12, and the toll-like receptor agonists. Retinoids and histone deacetylase inhibitors, widely used therapies in early stage CTCL, have been shown to modulate immune effector mechanisms. For most patients with CTCL, the goals of therapy are to exploit immunotherapeutic approaches for as long as possible and to keep immune function intact.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Edelson R, Berger C, Gasparro F, et al. Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy. Preliminary results. N Engl J Med. 1987;316:297–303.

    Article  PubMed  CAS  Google Scholar 

  2. Knobler R, Barr ML, Couriel DR, et al. Extracorporeal photopheresis: past, present, and future. J Am Acad Dermatol. 2009;61:652–65.

    Article  PubMed  Google Scholar 

  3. Berger C, Hoffmann K, Vasquez JG, et al. Rapid generation of maturationally synchronized human dendritic cells: contribution to the clinical efficacy of extracorporeal photochemotherapy. Blood. 2010;116:4838–47.

    Article  PubMed  CAS  Google Scholar 

  4. 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. 2008;158:659–78.

    Article  PubMed  CAS  Google Scholar 

  5. Lansigan F, Foss FM. Current and emerging treatment strategies for cutaneous T-cell lymphoma. Drugs. 2010;70:273–86.

    Article  PubMed  CAS  Google Scholar 

  6. Wilson LD, Jones GW, Kim D, et al. Experience with total skin electron beam therapy in combination with extracorporeal photopheresis in the management of patients with erythrodermic (T4) mycosis fungoides. J Am Acad Dermatol. 2000;43:54–60.

    Article  PubMed  CAS  Google Scholar 

  7. Suchin KR, Cucchiara AJ, Gottleib SL, et al. Treatment of cutaneous T-cell lymphoma with combined immunomodulatory therapy: a 14-year experience at a single institution. Arch Dermatol. 2002;138:1054–60.

    Article  PubMed  Google Scholar 

  8. Dippel E, Schrag H, Goerdt S, Orfanos CE. Extracorporeal photopheresis and interferon-alpha in advanced cutaneous T-cell lymphoma. Lancet. 1997;350:32–3.

    Article  PubMed  CAS  Google Scholar 

  9. Wollina U, Looks A, Meyer J, et al. Treatment of stage II cutaneous T-cell lymphoma with interferon alfa-2a and extracorporeal photochemotherapy: a prospective controlled trial. J Am Acad Dermatol. 2001;44:253–60.

    Article  PubMed  CAS  Google Scholar 

  10. Lim HW, Harris HR. Etretinate as an effective adjunctive therapy for recalcitrant palmar/plantar hyperkeratosis in patients with erythrodermic cutaneous T cell lymphoma undergoing photopheresis. Dermatol Surg. 1995;21:597–9.

    Article  PubMed  CAS  Google Scholar 

  11. Zackheim HS, Epstein Jr EH. Low-dose methotrexate for the Sezary syndrome. J Am Acad Dermatol. 1989;21:757–62.

    Article  PubMed  CAS  Google Scholar 

  12. Suchin KR, Cassin M, Gottleib SL, et al. Increased interleukin 5 production in eosinophilic Sezary syndrome: regulation by interferon alfa and interleukin 12. J Am Acad Dermatol. 2001;44:28–32.

    Article  PubMed  CAS  Google Scholar 

  13. Borden EC, Sen GC, Uze G, et al. Interferons at age 50: past, current and future impact on biomedicine. Nat Rev Drug Discov. 2007;6:975–90.

    Article  PubMed  CAS  Google Scholar 

  14. Bunn Jr PA, Foon KA, Ihde DC, et al. Recombinant leukocyte A interferon: an active agent in advanced cutaneous T-cell lymphomas. Ann Intern Med. 1984;101:484–7.

    PubMed  Google Scholar 

  15. Olsen EA, Rosen ST, Vollmer RT, et al. Interferon alfa-2a in the treatment of cutaneous T cell lymphoma. J Am Acad Dermatol. 1989;20:395–407.

    Article  PubMed  CAS  Google Scholar 

  16. Papa G, Tura S, Mandelli F, et al. Is interferon alpha in cutaneous T-cell lymphoma a treatment of choice? Br J Haematol. 1991;79 Suppl 1:48–51.

    Article  PubMed  Google Scholar 

  17. Olsen EA. Interferon in the treatment of cutaneous T-cell lymphoma. Dermatol Ther. 2003;16:311–21.

    Article  PubMed  Google Scholar 

  18. Wolff JM, Zitelli JA, Rabin BS, Smiles KA, Abell E. Intralesional interferon in the treatment of early mycosis fungoides. J Am Acad Dermatol. 1985;13:604–12.

    Article  PubMed  CAS  Google Scholar 

  19. Springer EA, Kuzel TM, Variakojis D, Kaul K, Rosen ST, Roenigk Jr HH. Correlation of clinical responses with immunologic and morphologic characteristics in patients with cutaneous T-cell lymphoma treated with interferon alfa-2a. J Am Acad Dermatol. 1993;29:42–6.

    Article  PubMed  CAS  Google Scholar 

  20. Steis RG, Smith 2nd JW, Urba WJ, et al. Resistance to recombinant interferon alfa-2a in hairy-cell leukemia associated with neutralizing anti-interferon antibodies. N Engl J Med. 1988;318:1409–13.

    Article  PubMed  CAS  Google Scholar 

  21. Itri LM, Sherman MI, Palleroni AV, et al. Incidence and clinical significance of neutralizing antibodies in patients receiving recombinant interferon-alpha 2a. J Interferon Res. 1989;9 Suppl 1:S9–15.

    PubMed  Google Scholar 

  22. Olsen EA, Bunn PA. Interferon in the treatment of cutaneous T-cell lymphoma. Hematol Oncol Clin North Am. 1995;9:1089–107.

    PubMed  CAS  Google Scholar 

  23. Rook AH, Kuzel TM, Olsen EA. Cytokine therapy of cutaneous T-cell lymphoma: interferons, interleukin-12, and interleukin-2. Hematol Oncol Clin North Am. 2003;17:1435–48. ix.

    Article  PubMed  Google Scholar 

  24. Dummer R, Hassel JC, Fellenberg F, et al. Adenovirus-mediated intralesional interferon-gamma gene transfer induces tumor regressions in cutaneous lymphomas. Blood. 2004;104:1631–8.

    Article  PubMed  CAS  Google Scholar 

  25. Heinzerling L, Kunzi V, Oberholzer PA, Kundig T, Naim H, Dummer R. Oncolytic measles virus in cutaneous T-cell lymphomas mounts antitumor immune responses in vivo and targets interferon-resistant tumor cells. Blood. 2005;106:2287–94.

    Article  PubMed  CAS  Google Scholar 

  26. Duvic M, Sherman ML, Wood GS, et al. A phase II open-label study of recombinant human interleukin-12 in patients with stage IA, IB, or IIA mycosis fungoides. J Am Acad Dermatol. 2006;55:807–13.

    Article  PubMed  Google Scholar 

  27. Gaffen SL, Liu KD. Overview of interleukin-2 function, production and clinical applications. Cytokine. 2004;28:109–23.

    Article  PubMed  CAS  Google Scholar 

  28. Foss FM, Borkowski TA, Gilliom M, et al. Chimeric fusion protein toxin DAB486IL-2 in advanced mycosis fungoides and the Sezary syndrome: correlation of activity and interleukin-2 receptor expression in a phase II study. Blood. 1994;84:1765–74.

    PubMed  CAS  Google Scholar 

  29. Lansigan F, Stearns DM, Foss F. Role of denileukin diftitox in the treatment of persistent or recurrent cutaneous T-cell lymphoma. Cancer Manag Res. 2010;2:53–9.

    PubMed  CAS  Google Scholar 

  30. Kadin ME, Vonderheid EC. Targeted therapies: Denileukin diftitox–a step towards a ‘magic bullet’ for CTCL. Nat Rev Clin Oncol. 2010;7:430–2.

    Article  PubMed  CAS  Google Scholar 

  31. 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. 2010;28:1870–7.

    Article  PubMed  CAS  Google Scholar 

  32. 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. 2001;19:376–88.

    PubMed  CAS  Google Scholar 

  33. Gorgun G, Foss F. Immunomodulatory effects of RXR rexinoids: modulation of high-affinity IL-2R expression enhances susceptibility to denileukin diftitox. Blood. 2002;100:1399–403.

    Article  PubMed  CAS  Google Scholar 

  34. Foss F, 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;106:454–7.

    Article  PubMed  CAS  Google Scholar 

  35. Medzhitov R. Toll-like receptors and innate immunity. Nat Rev Immunol. 2001;1:135–45.

    Article  PubMed  CAS  Google Scholar 

  36. Jurk M, Heil F, Vollmer J, et al. Human TLR7 or TLR8 independently confer responsiveness to the antiviral compound R-848. Nat Immunol. 2002;3:499.

    Article  PubMed  CAS  Google Scholar 

  37. Krieg AM. CpG motifs: the active ingredient in bacterial extracts? Nat Med. 2003;9:831–5.

    Article  PubMed  CAS  Google Scholar 

  38. Heil F, Hemmi H, Hochrein H, et al. Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science. 2004;303:1526–9.

    Article  PubMed  CAS  Google Scholar 

  39. Martinez-Gonzalez MC, Verea-Hernando MM, Yebra-Pimentel MT, Del Pozo J, Mazaira M, Fonseca E. Imiquimod in mycosis fungoides. Eur J Dermatol. 2008;18:148–52.

    PubMed  Google Scholar 

  40. Dummer R, Urosevic M, Kempf W, Kazakov D, Burg G. Imiquimod induces complete clearance of a PUVA-resistant plaque in mycosis fungoides. Dermatology. 2003;207:116–8.

    Article  PubMed  Google Scholar 

  41. Lonsdorf AS, Kuekrek H, Stern BV, Boehm BO, Lehmann PV, Tary-Lehmann M. Intratumor CpG-oligodeoxynucleotide injection induces protective antitumor T cell immunity. J Immunol. 2003;171:3941–6.

    PubMed  CAS  Google Scholar 

  42. Wysocka M, Benoit BM, Newton S, Azzoni L, Montaner LJ, Rook AH. Enhancement of the host immune responses in cutaneous T-cell lymphoma by CpG oligodeoxynucleotides and IL-15. Blood. 2004;104:4142–9.

    Article  PubMed  CAS  Google Scholar 

  43. Kim YH, Girardi M, Duvic M, et al. Phase I trial of a Toll-like receptor 9 agonist, PF-3512676 (CPG 7909), in patients with treatment-refractory, cutaneous T-cell lymphoma. J Am Acad Dermatol. 2010;63:975–83.

    Article  PubMed  CAS  Google Scholar 

  44. Tang XH, Gudas LJ. Retinoids, retinoic acid receptors, and cancer. Annu Rev Pathol. 2011;6:345–64.

    Article  PubMed  CAS  Google Scholar 

  45. Fontana JA, Rishi AK. Classical and novel retinoids: their targets in cancer therapy. Leukemia. 2002;16:463–72.

    Article  PubMed  CAS  Google Scholar 

  46. Meunier L, Bohjanen K, Voorhees JJ, Cooper KD. Retinoic acid upregulates human Langerhans cell antigen presentation and surface expression of HLA-DR and CD11c, a beta 2 integrin critically involved in T-cell activation. J Invest Dermatol. 1994;103:775–9.

    Article  PubMed  CAS  Google Scholar 

  47. Kempf W, Kettelhack N, Duvic M, Burg G. Topical and systemic retinoid therapy for cutaneous T-cell lymphoma. Hematol Oncol Clin North Am. 2003;17:1405–19.

    Article  PubMed  Google Scholar 

  48. Foss FM, Waldmann TA. Interleukin-2 receptor-directed therapies for cutaneous lymphomas. Hematol Oncol Clin North Am. 2003;17:1449–58.

    Article  PubMed  Google Scholar 

  49. Fox FE, Kubin M, Cassin M, et al. Retinoids synergize with interleukin-2 to augment IFN-gamma and interleukin-12 production by human peripheral blood mononuclear cells. J Interferon Cytokine Res. 1999;19:407–15.

    Article  PubMed  CAS  Google Scholar 

  50. Pigatto PD, Bersani L, Colotta F, Morelli M, Altomare GF, Polenghi MM. Effect of retinoids on natural killer cell activity. Arch Dermatol Res. 1986;278:507–9.

    Article  PubMed  CAS  Google Scholar 

  51. Gordy C, Dzhagalov I, He YW. Regulation of CD8(+) T cell functions by RARgamma. Semin Immunol. 2009;21:2–7.

    Article  PubMed  CAS  Google Scholar 

  52. Heald P, Mehlmauer M, Martin AG, Crowley CA, Yocum RC, Reich SD. 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. 2003;49:801–15.

    Article  PubMed  Google Scholar 

  53. 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. 2001;19:2456–71.

    PubMed  CAS  Google Scholar 

  54. Duvic M, Martin AG, Kim Y, et al. Phase 2 and 3 clinical trial of oral bexarotene (Targretin capsules) for the treatment of refractory or persistent early-stage cutaneous T-cell lymphoma. Arch Dermatol. 2001;137:581–93.

    PubMed  CAS  Google Scholar 

  55. Lin JH, Kim EJ, Bansal A, et al. Clinical and in vitro resistance to bexarotene in adult T-cell leukemia: loss of RXR-alpha receptor. Blood. 2008;112:2484–8.

    Article  PubMed  CAS  Google Scholar 

  56. Choudhary C, Kumar C, Gnad F, et al. Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009;325:834–40.

    Article  PubMed  CAS  Google Scholar 

  57. Mercurio C, Minucci S, Pelicci PG. Histone deacetylases and epigenetic therapies of hematological malignancies. Pharmacol Res. 2010;62:18–34.

    Article  PubMed  CAS  Google Scholar 

  58. Piekarz RL, Robey RW, Zhan Z, et al. T-cell lymphoma as a model for the use of histone deacetylase inhibitors in cancer therapy: impact of depsipeptide on molecular markers, therapeutic targets, and mechanisms of resistance. Blood. 2004;103:4636–43.

    Article  PubMed  CAS  Google Scholar 

  59. Tiffon C, Adams J, van der Fits L, et al. The histone deacetylase inhibitors vorinostat and romidepsin downmodulate IL-10 expression in cutaneous T-cell lymphoma cells. Br J Pharmacol. 2011;162:1590–602.

    Article  PubMed  CAS  Google Scholar 

  60. Shao RH, Tian X, Gorgun G, Urbano AG, Foss FM. Arginine butyrate increases the cytotoxicity of DAB(389)IL-2 in leukemia and lymphoma cells by upregulation of IL-2Rbeta gene. Leuk Res. 2002;26:1077–83.

    Article  PubMed  CAS  Google Scholar 

  61. Wang L, de Zoeten EF, Greene MI, Hancock WW. Immunomodulatory effects of deacetylase inhibitors: therapeutic targeting of FOXP3+ regulatory T cells. Nat Rev Drug Discov. 2009;8:969–81.

    PubMed  CAS  Google Scholar 

  62. Kelly-Sell M BB, Kim Y, Harrison C, Sutherland K, Showe L, Maria W, Rook A. The histone deacetylase inhibitor, romidepsin, suppresses in vivo immune functions of cutaneous T-cell lymphoma patients. J Invest Dermatol. 2011;131:Suppl; abstr 520.

    Google Scholar 

  63. 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. 2007;25:3109–15.

    Article  PubMed  CAS  Google Scholar 

  64. 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. 2009;27:5410–7.

    Article  PubMed  CAS  Google Scholar 

  65. Whittaker SJ, Demierre MF, Kim EJ, et al. Final results from a multicenter, international, pivotal study of romidepsin in refractory cutaneous T-cell lymphoma. J Clin Oncol. 2010;28:4485–91.

    Article  PubMed  CAS  Google Scholar 

  66. Bates SE, Rosing DR, Fojo T, Piekarz RL. Challenges of evaluating the cardiac effects of anticancer agents. Clin Cancer Res. 2006;12:3871–4.

    Article  PubMed  CAS  Google Scholar 

  67. Piekarz RL, Frye AR, Wright JJ, et al. Cardiac studies in patients treated with depsipeptide, FK228, in a phase II trial for T-cell lymphoma. Clin Cancer Res. 2006;12:3762–73.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Dermatology, Yale University School of Medicine, New Haven, CT, USA

    Badri Modi, Richard L. Edelson & Michael Girardi

  2. Department of Medical Oncology/Hematology, Yale University School of Medicine, 333 Cedar Street, FMP 130, 208032, New Haven, CT, USA, 06520

    Francine Foss

Authors
  1. Badri Modi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Francine Foss
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Richard L. Edelson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael Girardi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Francine Foss .

Editor information

Editors and Affiliations

  1. Yale University School of Medicine, Dept. of Medical Oncology/Hematology, Cedar Street 333, New Haven, 06520, Connecticut, USA

    Francine Foss

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Modi, B., Foss, F., Edelson, R.L., Girardi, M. (2013). Immunotherapy for Cutaneous T-Cell Lymphoma. In: Foss, F. (eds) T-Cell Lymphomas. Contemporary Hematology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-170-7_18

Download citation

  • DOI: https://doi.org/10.1007/978-1-62703-170-7_18

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-169-1

  • Online ISBN: 978-1-62703-170-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation