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Newer Treatment Options Under Study for Advanced Cutaneous T-Cell Lymphomas

By: Sarah Campen, PharmD
Posted: Monday, August 12, 2019

Although many patients with early cutaneous T-cell lymphoma have slow-progressing disease, the prognosis for those with advanced stages of disease is poor. An article published in Frontiers in Medicine reviewed the myriad of currently used and future therapies under study for patients with advanced mycosis fungoides and Sézary syndrome.

“Current treatment outcome is characterized by high relapse rates and low durable remission rates,” stated Tomonori Oka, PhD, and Tomomitsu Miyagaki, PhD, of the University of Tokyo, Japan. “As treatment of advanced-stage [cutaneous T-cell lymphoma] is mostly palliative and not curable, a stage-based approach utilizing sequential therapies in an escalated manner is currently favorable.” However, the only option for curing mycosis fungoides and Sézary syndrome is stem cell transplantation.

Three humanized immunoglobulin G1 monoclonal antibodies are under study for cutaneous T-cell lymphoma. Mogamulizumab significantly increased the overall rate of response and prolonged progression-free survival compared with vorinostat in patients with relapsed or refractory disease in the phase III MAVORIC trial. Research also suggests that low-dose alemtuzumab may be an effective treatment for erythrodermic mycosis fungoides and Sézary syndrome. The investigational monoclonal antibody IPH4102 targets the immunoglobulin-like receptor KIR3DL2. The relative specific expression of KIR3DL2 on malignant cutaneous T-cell lymphoma cells makes it a potential therapeutic target.

The antibody-drug conjugate brentuximab vedotin seems to be a preferable treatment option for mycosis fungoides when biopsy samples have 10% or more CD30-positive malignant cells.

Pralatrexate has improved antitumor activity compared with another antineoplastic folate analog, methotrexate. According to the authors, it appears to be a “promising” treatment with the potential to provide lasting benefit with relatively low toxicity. Forodesine, an inhibitor of purine nucleoside phosphorylase, is another agent under investigation. However, limited activity observed in early studies and a high rate of grade 3 or 4 lymphopenia may restrict its use.

Several ongoing clinical trials using immune checkpoint inhibitors, including nivolumab, ipilimumab, and durvalumab, are underway; lenalidomide and everolimus have also demonstrated activity in refractory disease. Novel agents denileukin diftitox and duvelisib appear to have clinical activity based on phase I trials, and further studies are continuing. 

Disclosure: The study authors reported no conflicts of interest.



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