Antibody-Based Therapies for Cutaneous T-Cell Lymphoma
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.
Compliance with Ethical Standards
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.
- 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.CrossRefGoogle 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.CrossRefGoogle 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.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.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.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.