Investigative drugs for the treatment of cutaneous T-cell lymphomas (CTCL): an update

ABSTRACT

Introduction: Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of skin-homing T-cell neoplasms, which represent approximately 75% of all primary cutaneous lymphomas. Mycosis fungoides and Sézary syndrome are the most common CTCL. Early stage disease follows a protracted course, carries a 5-year disease specific survival of 97% and can be treated with skin-directed therapies. Widespread, advanced disease has a 5-year OS of less than 25% and necessitates systemic treatment. Allogeneic stem cell transplantation is a potentially curative treatment option for advanced CTCL, however, transplant-related morbidity and mortality must be considered and a risk-benefit assessment performed on individual basis.

Areas covered: Herein, we provide a review of investigative drugs in early-stage trials for the treatment of cutaneous CTCL, including topically applied immunomodulators such as replicating herpes virus or toll-like receptor 7/8 agonist resiquimod and systemic therapies with monoclonal antibodies, such as anti-CD47, recombinant cytotoxic interleukin 2 fusion protein anti-KIR3DL2 antibody and anti-miR-155 antibody.

Expert Opinion: Among the reviewed drugs, resiquimod shows promising clinical efficacy with good tolerability in early CTCL. In refractory or relapsed disease, intratumoral anti-CD47-, anti-CCR4- and anti-KIR3DL2-antibodies show high response rates, however, latter two also show considerable toxicity. Larger trials are needed to better evaluate the discussed therapies.

KEYWORDS:

• Antibodies
• CTCL
• MF
• immunotherapy
• sézary syndrome
• targeted therapies

Article highlights

• Therapies implicated in CTCL have limitations in efficacy and safety, hence new treatment options are needed

• Clinical trials investigate skin-directed therapies for early disease and systemic therapies for advanced cases

• Drugs, directly affecting tumor cells and those, directed to immune system are in development

• Drugs in clinical trials show promising results, but larger studies are needed

• Numerous compounds are still in pre-clinical development and will enter clinical trials in near future

• This box summarizes key points contained in the article.

Declaration of interest

R Dummer has intermittent, project focused consulting and/or advisory relationships with Novartis, Merck Sharp & Dhome (MSD), Bristol-Myers Squibb (BMS), Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome outside the submitted work. E Guenova has received honoraria and grant support from Takeda, Helsinn, and Mallinckrodt. 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

One of the reviewers on this paper acts on a speaker’s bureau for Seattle Genetics. Two additional reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.