Novel therapeutic approaches for cutaneous T cell lymphomas

ABSTRACT

Introduction: Cutaneous T-cell lymphoma (CTCL) is a rare non-Hodgkin’s lymphoma, characterized by malignant T cells infiltrating the skin. CTCL exhibits vast heterogeneity which complicates diagnosis and therapeutic strategies. Current CTCL treatment includes skin-directed therapies (such as topical corticosteroid, topical mechlorethamine, topical bexarotene, ultraviolet phototherapy and localized radiotherapy), total skin electron beam therapy and systemic therapies. Elucidation of molecular and signaling pathways underlying CTCL pathogenesis leads to identification of innovative and personalized treatment schemes.

Areas covered: The authors reviewed the molecular and immunological aspects of CTCL with special focus on Mycosis Fungoides (MF), Sézary Syndrome (SS) and associated systemic treatment. A literature search was conducted in PubMed and Web of Science for peer-reviewed articles published until November 2020. Novel treatment approaches including retinoids, targeted therapies, immune checkpoint and JAK/STAT inhibitors, histones deacetylase (HDAC) and mTOR inhibitors as well as proteasome inhibitors, are discussed as potential therapeutic tools for the treatment of CTCL.

Expert opinion: Novel therapeutic agents exhibit potential beneficial effects in CTCL patients of high need for therapy such as refractory early stage cutaneous and advanced stage disease. Therapeutic schemes employing a combination of novel agents with current treatment options may prove valuable for the future management of CTCL patients.

KEYWORDS:

• MF
• SS
• target therapies
• immunomodulators
• JAK inhibitors
• HDAC inhibitors
• proteasome inhibitors

Article Highlights

• Target therapies, including mogamulizumab, brentuximab vedotin, alemtuzumab and IPH4102, exhibit sufficient ORR, without severe adverse events.

• Immunomodulators (pembrolizumab and ipilimumab) exhibit sufficient ORR with toxicity profile been restricted to immune-mediated adverse events.

• JAKi (ruxolitinib and tofacitinib) reduce cell viability of MF and SS cell lines and need further investigation in primary cells.

• HDACi (romidepsin and vorinostat) have been approved by FDA for CTCL treatment and resminostat is currently in a phase 2 clinical study.

• Proteasome inhibitors are emerging therapeutic agents for the treatment of CTCL, with bortezomib demonstrating beneficial effects.

• Primary data of JAKi, ruxolitinib and HDACi resminostat administration in cell lines support the significant effectiveness of combination therapies.

Declaration of interest

The authors declare that they have no conflict of interest regarding this work.

Additional information

Funding

This work did not receive any sort of financial assistance from funding agencies in the public, commercial, or not-for-profit sectors.