Skip to main content
SpringerLink
Log in

Antibody-Based Therapies for Cutaneous T-Cell Lymphoma

  • Review Article
  • Published:
American Journal of Clinical Dermatology Aims and scope Submit manuscript

Abstract

Cutaneous T-cell lymphomas (CTCLs) are a group of non-Hodgkin’s lymphomas that present in the skin. In early-stage disease, the course is generally chronic and indolent; however, in advanced stages of disease, therapies rarely provide long-lasting responses, and the only potential curative therapy is allogeneic hematopoietic stem-cell transplantation. This has led to the search for novel targeted therapies to better treat more advanced stages of CTCLs that cannot be controlled by typical treatment regimens. One area of advancement has been the development of antibodies specifically targeted to cell types that are known to be involved in CTCL. At present, brentuximab vedotin, an antibody–drug conjugate composed of an anti-cluster of differentiation (CD)-30 antibody covalently linked to monomethyl auristatin E, is approved for the treatment of CD30+ lymphoproliferative disorders [lymphomatoid papulosis (LyP) and primary cutaneous-anaplastic large-cell lymphoma (pc-ALCL)] as well as transformed CD30+ mycosis fungoides (MF). Additionally, mogamulizumab, an anti-chemokine receptor 4 (CCR4) monoclonal antibody, is approved for patients with MF or Sézary syndrome (SS) for whom one prior systemic therapy has failed. Trials are underway looking into the use of immune checkpoint inhibitors in the treatment of CTCLs. As we continue to research CTCL, and as antibody-based therapies continue to advance, more antibody-specific targeted therapy could provide alternative treatment regimens for patients with advanced CTCL.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Criscione VD, Weinstock MA. Incidence of cutaneous T-cell lymphoma in the United States, 1973–2002. Arch Dermatol. 2007;143(7):854–9.

    Article  PubMed  Google Scholar 

  2. Vollmer RT. A review of survival in mycosis fungoides. Am J Clin Pathol. 2014;141(5):706–11.

    Article  PubMed  Google Scholar 

  3. 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. 2010;28(31):4730–9.

    Article  PubMed  Google Scholar 

  4. Scarisbrick JJ, Prince HM, Vermeer MH, et al. Cutaneous lymphoma international consortium study of 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. 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. 2012;18(18):5051–60.

    Article  CAS  PubMed  Google Scholar 

  6. 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 Sézary syndrome. J Clin Oncol. 2010;28(14):2365–72.

    Article  PubMed  Google Scholar 

  7. Francisco JA, Cerveny CG, Meyer DL, et al. cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity. Blood. 2003;102(4):1458–65.

    Article  CAS  PubMed  Google Scholar 

  8. Van de Donk NW, Dhimolea E. Brentuximab vedotin. MAbs. 2012;4(4):458–65.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Withers DR, Gaspal FM, Bekiaris V, et al. OX40 and CD30 signals in CD4(+) T-cell effector and memory function: a distinct role for lymphoid tissue inducer cells in maintaining CD4(+) T-cell memory but not effector function. Immunol Rev. 2011;244(1):134–48.

    Article  CAS  PubMed  Google Scholar 

  10. Duvic M, Tetzlaff MT, Gangar P, Clos AL, Sui D, Talpur R. Results of a phase II trial of brentuximab vedotin for CD30+ cutaneous T-Cell lymphoma and lymphomatoid papulosis. J Clin Oncol. 2015;33(32):3759–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kim YH, Tavallaee M, Sundram U, 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Prince HM, Kim YH, Horwitz SM, ALCANZA Study Group, et al. Brentuximab vedotin or physician’s choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial. Lancet. 2017;390(10094):555–66.

    Article  CAS  PubMed  Google Scholar 

  13. Duvic M, Reddy SA, Pinter-brown L, et al. A phase II study of SGN-30 in cutaneous anaplastic large cell lymphoma and related lymphoproliferative disorders. Clin Cancer Res. 2009;15(19):6217–24.

    Article  CAS  PubMed  Google Scholar 

  14. Forero-torres A, Leonard JP, Younes A, et al. A Phase II study of SGN-30 (anti-CD30 mAb) in Hodgkin lymphoma or systemic anaplastic large cell lymphoma. Br J Haematol. 2009;146(2):171–9.

    Article  CAS  PubMed  Google Scholar 

  15. Andrew DP, Ruffing N, Kim CH, et al. C-C chemokine receptor 4 expression defines a major subset of circulating nonintestinal memory T cells of both Th1 and Th2 potential. J Immunol. 2001;166(1):103–11.

    Article  CAS  PubMed  Google Scholar 

  16. Kakinuma T, Sugaya M, Nakamura K, et al. Thymus and activation-regulated chemokine (TARC/CCL17) in mycosis fungoides: serum TARC levels reflect the disease activity of mycosis fungoides. J Am Acad Dermatol. 2003;48(1):23–30.

    Article  PubMed  Google Scholar 

  17. Niwa R, Shoji-hosaka E, Sakurada M, et al. Defucosylated chimeric anti-CC chemokine receptor 4 IgG1 with enhanced antibody-dependent cellular cytotoxicity shows potent therapeutic activity to T-cell leukemia and lymphoma. Cancer Res. 2004;64(6):2127–33.

    Article  CAS  PubMed  Google Scholar 

  18. Ito A, Ishida T, Yano H, et al. Defucosylated anti-CCR4 monoclonal antibody exercises potent ADCC-mediated antitumor effect in the novel tumor-bearing humanized NOD/Shi-scid, IL-2Rgamma(null) mouse model. Cancer Immunol Immunother. 2009;58(8):1195–206.

    Article  CAS  PubMed  Google Scholar 

  19. Duvic M, Pinter-brown LC, Foss FM, 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ogura M, Ishida T, Hatake 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.

    Article  CAS  PubMed  Google Scholar 

  21. Kim 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. Blood. 2017;130(Suppl 1):817. Accessed 31 July 2018.

  22. Dai J, Almazan TH, Hong EK, et al. Potential association of anti-CCR4 antibody mogamulizumab and graft-vs-host disease in patients with mycosis fungoides and Sézary syndrome. JAMA Dermatol. 2018;154(6):728–30.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Trautinger F, Eder J, Assaf C, et al. European organisation for research and treatment of cancer consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome—update 2017. Eur J Cancer. 2017;77:57–74.

    Article  PubMed  Google Scholar 

  24. Hale G, Dyer MJ, Clark MR, et al. Remission induction in non-Hodgkin lymphoma with reshaped human monoclonal antibody CAMPATH-1H. Lancet. 1988;2(8625):1394–9.

    Article  CAS  PubMed  Google Scholar 

  25. Ginaldi L, De Martinis M, Matutes E, et al. Levels of expression of CD52 in normal and leukemic B and T cells: correlation with in vivo therapeutic responses to Campath-1H. Leuk Res. 1998;22(2):185–91.

    Article  CAS  PubMed  Google Scholar 

  26. Coles AJ, Compston DA, Selmaj KW, et al. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med. 2008;359(17):1786–801.

    Article  PubMed  Google Scholar 

  27. Lundin J, Hagberg H, Repp R, 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.

    Article  CAS  PubMed  Google Scholar 

  28. Querfeld C, Mehta N, Rosen ST, et al. Alemtuzumab for relapsed and refractory erythrodermic cutaneous T-cell lymphoma: a single institution experience from the Robert H. Lurie Comprehensive Cancer Center. Leuk Lymphoma. 2009;50(12):1969–76.

    Article  CAS  PubMed  Google Scholar 

  29. 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. 2014;170(3):720–4.

    Article  CAS  PubMed  Google Scholar 

  30. Zinzani PL, Alinari L, Tani M, et al. Preliminary observations of a phase II study of reduced-dose alemtuzumab treatment in patients with pretreated T-cell lymphoma. Haematologica. 2005;90:702–3.

    CAS  PubMed  Google Scholar 

  31. Bernengo MG, Quaglino P, Comessatti A, 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.

    Article  CAS  PubMed  Google Scholar 

  32. Clark RA, Watanabe R, Teague JE, 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Nevet MJ, Zuckerman T, Sahar D, Bergman R. Transformation of Sézary syndrome into CD30+ anaplastic large T-cell lymphoma after alemtuzumab therapy with evidence of clonal unity. Am J Dermatopathol. 2015;37(1):73–7.

    Article  PubMed  Google Scholar 

  34. Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677–704.

    Article  CAS  PubMed  Google Scholar 

  35. Kantekure K, Yang Y, Raghunath P, et al. 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(1):126–8.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Lesokhin AM, Ansell SM, Armand P, et al. Nivolumab in patients with relapsed or refractory hematologic malignancy: preliminary results of a phase Ib study. J Clin Oncol. 2016;34(23):2698–704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Khodadoust M, Rook AH, Porcu P, Foss FM, Moskowitz AJ, Shustov AR, et al. Pembrolizumab for treatment of relapsed/refractory mycosis fungoides and Sézary syndrome: clinical efficacy in a CITN multicenter phase 2 study. Blood. 2016;128(22):181.

    Google Scholar 

  38. Waldmann TA, Goldman CK, Bongiovanni KF, et al. Therapy of patients with human T-cell lymphotrophic virus I-induced adult T-cell leukemia with antiTac, a monoclonal antibody to the receptor for interleukin-2. Blood. 1988;72:1805–16.

    CAS  PubMed  Google Scholar 

  39. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. 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(11):1870–7.

    Article  CAS  PubMed  Google Scholar 

  41. Kim YH, Duvic M, Obitz E, et al. Clinical efficacy of zanolimumab (HuMax-CD4): two phase 2 studies in refractory cutaneous T-cell lymphoma. Blood. 2007;109(11):4655–62.

    Article  CAS  PubMed  Google Scholar 

  42. Deirdre O’Mahony et al. Phase I trial of siplizumab in CD2-positive lymphoproliferative disease. Blood. 2005;106(11):3353. http://www.bloodjournal.org/content/106/11/3353. Accessed 31 July 2018.

  43. Deirdre O’Mahony et al. EBV-related lymphoproliferative disease complicating therapy with siplizumab, a novel anti-CD2 mediated T- and NK-cell depleting agent, in patients with T-cell malignancies. Blood. 2007;110(11):3565. http://www.bloodjournal.org/content/110/11/3565. Accessed 31 July 2018.

Download references

Author information

Authors and Affiliations

  1. University of Texas McGovern Medical School, Houston, TX, USA

    Macartney Welborn

  2. University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1452, Houston, TX, 77030-4009, USA

    Madeleine Duvic

Authors
  1. Macartney Welborn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Madeleine Duvic
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Macartney Welborn.

Ethics declarations

Funding

No sources of funding were used to conduct this study or prepare this manuscript.

Conflict of Interest

Madeleine Duvic is science and advisory committee member for Millennium Pharmaceuticals, consulting and science advisor for Kyowa Pharmaceuticals, and on the advisory board for Seattle Genetics. Macartney Welborn has no conflicts of interest that are directly relevant to the content of this article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Welborn, M., Duvic, M. Antibody-Based Therapies for Cutaneous T-Cell Lymphoma. Am J Clin Dermatol 20, 115–122 (2019). https://doi.org/10.1007/s40257-018-0402-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40257-018-0402-5

Search

Navigation