Antibody-Based Therapies for Cutaneous T-Cell Lymphoma

Macartney Welborn; Madeleine Duvic

Disclosures

Am J Clin Dermatol. 2019;20(1):115-122. 

In This Article

Abstract and Introduction

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 longlasting 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.

Introduction

Cutaneous T-cell lymphomas (CTCLs) are a group of non-Hodgkin's lymphomas that present in the skin and are commonly mistaken for chronic eczema or psoriasis. The reported annual incidence of CTCL is 6.4 per million individuals.[1] The most common (~ 70%) CTCL is mycosis fungoides (MF), which usually presents as pruritic patches and plaques. With early-stage disease, the course is generally chronic and indolent with a 10-year survival rate of approximately 86% for patients with stage T1 MF.[2] However, reports have shown that up to 34% of early-stage patients will have disease progression to advanced-stage MF (stage T3–4) with a 10-year survival rate ranging from 0.1 to 42%.[2–5] Treatment of the early stages of disease is focused on skin-directed therapy, which often controls symptoms. However, in advanced stages of disease, therapies rarely provide long-lasting responses, and the only potential curative therapy is allogeneic hematopoietic stem-cell transplantation.[6] 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 monoclonal antibodies specifically targeted to cell types that are known to be involved in CTCL (Table 1). Both the US FDA and the European Medicines Agency have approved brentuximab vedotin, an antibody–drug conjugate directed at cluster of differentiation (CD)-30+ cells and mogamulizumab, a defucosylated, humanized anti-chemokine receptor 4 (CCR4) monoclonal antibody for the treatment of CTCL. Other antibodies, including alemtuzumab, an antibody targeting CD52, and the well-known class of immune checkpoint inhibitors, are currently being studied. This article reviews the mechanism of action and clinical trials of antibody-based therapies being developed for the treatment of CTCL.

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