New nonchemotherapy treatment options for cutaneous T-cell lymphomas

ABSTRACT

Introduction

The most common types of CTCL are mycosis fungoides (MF) and Sézary syndrome (SS). In both MF and SS, complete responses to treatment are uncommon. Recent developments and understanding of the biology of MF/SS have led to novel agents which may offer prolonged responses with less toxicity compared to conventional chemotherapy approaches.

Areas Covered

In this review, we discuss the efficacy and safety of new nonchemotherapy treatment options including antibody agents, small molecule inhibitors, fusion proteins, and CAR T-cell therapy. We also reflect on older immunomodulatory treatments including retinoids and histone deacetylase inhibitors.

Expert Opinion

Patients with MF/SS who require systemic therapy often progress through multiple agents sequentially, thus the need for additional novel agents in the treatment armamentarium. Antibody-based therapies such as alemtuzumab are highly effective in the blood compartment of disease, while brentuximab vedotin has shown higher activity in skin and lymph nodes. Checkpoint inhibitors may play a role in treating MF/SS but may induce hyperprogression, and engineered T cells and bispecific antibodies recruiting immune effectors are being developed and may show promise in the future.

KEYWORDS:

• Cutaneous T cell lymphoma
• mycosis fungoides
• Sezary syndrome
• mogamulizumab
• brentuximab vedotin
• immunotherapy
• photopheresis

Article highlights

• Novel, nonchemotherapy agents have shown activity in patients with relapsed/refractory mycosis fungoides/Sezary syndrome, but response rates may be different for MF and SS patients with newer agents.

• Antibodies such as mogamulizumab and alemtuzumab have significant activity on the blood compartment and are associated with improvement in skin manifestations and quality of life measures (i.e. Skindex-29 pruritis). Improvements in overall survival are unknown as the clinical trials have used ORR as primary end point.

• Novel immunotherapy approaches with checkpoint inhibitors have shown activity but also disease flare in some patients.

• Engineered T cell therapies are being explored in MF/SS but T cell fratricide is a major obstacle for many of these approaches.

Declaration of interest

F Foss is a member of the advisory boards of Seattle Genetics, Acrotech, Miragen, Kura and Eisai. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

A reviewer has disclosed that they have received consultation fees from Takeda, Kyowa and Recordati. All other peer reviewers in this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.