Chlormethine Gel for the Treatment of Mycosis Fungoides

Abstract and Introduction

Abstract

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL), representing almost 50% of all lymphomas arising in the skin. There is an unmet need in the treatment of MF in Canada, as current available therapies for early-stage MF are limited, without topical agents previously indicated. Chlormethine gel is a topical antineoplastic agent with phase II clinical trial and real-world data demonstrating safety and efficacy as a treatment option for adults with MF. Skin-related side effects such as dermatitis can be managed through appropriate strategies. The use of chlormethine gel can be considered for patients with stage IA and IB MF-CTCL as it provides an easily administered, skin-directed treatment option that fills an unmet need in Canada.

Introduction

Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma (CTCL), which primarily manifests in the skin.^[1–5] The prognosis of MF depends on the type and extent of skin lesions and extracutaneous disease.^[6] In early stages (IA-IIA), the lesions comprise red, scaly patches or plaques and as disease progresses to late stages (≥IIB), the patients develop skin tumors, often with ulcerations.^[6] Diagnosis is often delayed as patients can experience several years of nonspecific skin changes that may resemble psoriasis or eczema.^[5,7]

MF typically affects adults with a median age at diagnosis of 55–60 years, and a male-to-female ratio of 1.6–2:1.^[8] In Canada, the annual national incidence of MF is estimated at 4 cases per million individuals per year, with a mortality rate of approximately 0.4 deaths per million annually observed from 1992 to 2010.^[9]

Early-stage MF patients represent approximately 70% of cases and most achieve normal life expectancy, with treatment aiming to prevent evolution to more severe disease and relieve burden on quality of life. Approximately 30% of patients progress to advanced disease (stage IIB or higher), and the 5-year survival rate is unfavorable: only 47% (stage IIB) to 18% (stage IVB). Many patients with MF experience comorbidities impacting their functional, emotional, and social well-being, such as cardiovascular events and secondary cancers.^[10–14] Currently, apart from allogeneic stem cell transplantation, there is no cure for MF, and treatment approaches focus on patients' health-related quality of life (HRQOL).^[10] In Canada, there remains an unmet need for novel MF therapies to address treatment gaps.

Chlormethine gel is a Health Canada approved topical antineoplastic agent for the treatment of stage IA and IB MF-CTCL in adult patients who have received prior skin-directed therapy.^[15] Regulatory approval for MF-CTCL has also been granted by the US FDA and European Medicines Agency. Evidence from a phase II clinical trial and real-world experience with chlormethine for over 30 years demonstrates chlormethine gel as a convenient topical agent with an efficacious and well-tolerated safety profile for adults.^[16–22]