Mechanism of action of chlormethine gel in mycosis fungoides

Abstract

Mycosis fungoides (MF), the most common type of cutaneous T‐cell lymphoma, is characterized by proliferation of malignant skin‐tropic T cells. Progression from early‐stage disease (skin patches and/or plaques) to more advanced stages (cutaneous tumours, erythroderma or extracutaneous involvement) occurs slowly and can be discontinuous. Prognosis is poor for the ~25% of patients who progress to advanced disease. Patients at any stage of MF may experience reduced health‐related quality of life (QoL) via a spectrum of physically and psychologically debilitating symptoms that can impact many aspects of daily life. Allogeneic stem‐cell transplantation is a curative treatment option for some patients with advanced disease, but otherwise there is currently no cure for MF; patients are often refractory to several treatments and require lifelong management. The goals of therapy are symptom control, prevention of disease progression, avoidance of treatment‐related toxicity and maintenance/improvement of QoL. Although treatment regimens exist it can be difficult to know how to prioritize them, hence therapies are tailored according to patient needs and drug availabilities, following clinical recommendations. International consensus guidelines recommend skin‐directed therapies (SDTs) as first‐line treatment for early‐stage disease, and SDTs combined with systemic therapy for advanced stages. Chlormethine (CL), also known as mechlorethamine, chlorethazine, mustine, HN2, caryolysine and embichin, is a synthetic deoxyribonucleic acid‐alkylating agent that was used as a chemical weapon (mustard gas) during the First World War. Subsequent investigation revealed that survivors of mustard gas exposure had lymphocytopenia, and that CL could inhibit rapidly proliferating malignant T cells. CL has since been developed as a topical treatment for MF and prescribed as such for over 70 years. This review aims to summarize the current knowledge regarding the mechanism of action of CL in the cutaneous micro‐environment, in the specific context of MF treatment.

Chlormethine gel in combination with other therapies for treatment of mycosis fungoides: a review with patient cases

“…Most of these patients experienced dermatitis during treatment. This long-term disease control may in part be caused by a unique effect that chlormethine appears to have on the disease evolution of MF ( 49 ). In the MIDAS study, patients were treated for 4 months, but CAILS improvements were still present after 5 and 12 months despite treatment discontinuation ( 26 ).…”

Advances in the treatment of mycoses fungoides and Sézary syndrome: a narrative update in skin-directed therapies and immune-based treatments

“…Chlormethine (CL) or mechlorethamine gel 0.016% was approved the United States (US) Food and Drug Administration (FDA) in 2013 for the treatment of adult patients with stage IA–IB MF. CL induces double-stranded DNA breaks, thereby inducing apoptosis in skin-homing malignant T-cells and suppressing the expression of DNA repair genes in malignant T cells in the skin ( 29 ). The recently reported real-world PROVe study assessed real-world efficacy of CL in daily clinical practice in the US ( 2 ).…”