Novel and Future Therapeutic Drugs for Advanced Mycosis Fungoides and Sézary Syndrome

Abstract

Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphoma. The majority of MF cases present with only patches and plaques and the lesions are usually limited to the skin. On the other hand, in some cases, patients show skin tumors or erythroderma followed by lymph node involvement and rarely visceral organ involvement. SS is a rare, aggressive cutaneous T-cell lymphoma marked by exfoliative erythroderma, lymphadenopathy, and leukemic blood involvement. Because patients with relapsed or refractory MF/SS display a poor prognosis and the current treatment options are characterized by high rates of relapse, there is unmet need for the efficient treatment. This review provides a discussion of the recent and future promising therapeutic approaches in the management of advanced MF/SS. These include mogamulizumab, brentuximab vedotin, alemtuzumab, immune checkpoint inhibitors, IPH4102 (anti-KIR3DL2 antibody), histone deacetylase inhibitors (vorinostat, romidepsin, panobinostat, belinostat, and resminostat), pralatrexate, forodesine, denileukin diftitox, duvelisib, lenalidomide, and everolimus.

Keywords: Sézary syndrome; clinical trial; mycosis fungoides; novel therapeutic agents; peripheral T-cell lymphoma.

Figure 1

History of clinical trials of single-agents which have been approved for cutaneous T-cell lymphoma or peripheral T-cell lymphoma by FDA, EMA, or PMDA. The data were collected on March 31, 2019. When the drug was approved as orphan drug from EMA, the comment “orphan” is added. CTCL, cutaneous T-cell lymphoma; PTCL, peripheral T-cell lymphoma; FDA, food and drug administration; EMA, European medicines agency; PMDA, pharmaceuticals and medical devices agency.

Figure 2

History of clinical trials of single-agents which have not been approved for cutaneous T-cell lymphoma or peripheral T-cell lymphoma by FDA, EMA, or PMDA. The data were collected on March 31, 2019. PI3K δ/γ I, phosphoinositide-3-kinase δ/γ inhibitor.