Monoclonal antibodies against cutaneous T-cell lymphomas

ABSTRACT

Introduction: Cutaneous T-cell lymphomas (CTCLs) comprise of a group of rare and heterogeneous skin lymphoproliferative disorders derived from skin resident T cells. Treatment of CTCLs is based on skin-directed approaches and/or systemic therapies. Advanced CTCLs are difficult to treat with the currently available treatments as they generally fail to obtain prolonged clinical remission. Recent studies concerning the pathogenetic mechanisms that are operative in CTCL have provided additional potential therapeutic targets for the treatment of these disorders. In particular, development of novel monoclonal antibodies against presumptive pathogenic molecules has resulted in targeted approaches to the clinical management of this group of lymphoproliferative disorders.

Areas covered: The following article examines the current and emerging monoclonal antibody-based therapies for CTCL, with a particular focus on mycosis fungoides, primary cutaneous anaplastic large cell CD30+ lymphoma and Sezary syndrome.

Expert opinion: These novel monoclonal antibodies may represent an innovative approach for targeted treatment of CTCL given their increased clinical efficacy and the acceptable toxicity profiles of most antibodies. In particular, anti-CD52, anti-CD30 and anti-CCR4 monoclonal antibodies represent the most promising agents with single agent activity, although the combination of these targeted monoclonal antibodies with other active agents deserves attention.

KEYWORDS:

• Cutaneous T-cell lymphomas
• immunotherapy
• monoclonal antibodies
• skin cancer
• target therapy

Article highlights

• The development of novel tumour-targeted and immune-targeted monoclonal antibodies has resulted in innovative approaches to the clinical management of this group of lymphoproliferative disorders.

• The anti-CD52 monoclonal antibody alemtuzumab may be responsible for long-term remission in patients with erythrodermic CTCL. In particular, alemtuzumab is efficacious and has a low toxicity profile when low doses are administered subcutaneously in short courses.

• Anti-CD30 monoclonal antibody-based therapy of CTCL indicates that the anti-CD30 mAb brentuximab vedotin represents a major therapeutic breakthrough toward the treatment of CD30-expressing CTCL.

• Mogamulizumab may represent a valid treatment alternative for patients with CCR4-positive relapsed/refractory CTCL either alone or in combination with other active agents.

• Therapeutic immune checkpoint blockade, in particular the PD1 pathway, using targeted monoclonal antibodies represents an exciting opportunity for advanced CTCL treatment.

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Declaration of interest

This author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This manuscript has not been funded.