Chlormethine Gel for the Treatment of Skin Lesions in All Stages of Mycosis Fungoides Cutaneous T-Cell Lymphoma: A Narrative Review and International Experience

Abstract

Mycosis fungoides (MF), the most common form of primary cutaneous T-cell lymphoma, is a disease typically with an indolent course that is initially characterized by localized patches and plaques. In the early stages of the disease, treatment involves skin-directed therapies (SDTs) such as topical corticosteroids and retinoids. Chlormethine gel (also known as mechlorethamine) was the first SDT purposely developed to treat MF and is currently endorsed by international guidelines for the treatment of adult patients with MF as a first-line therapy. While chlormethine is an efficacious therapy, its usage may be complicated by the development of cutaneous reactions at the sites of application. Herein, we discuss the supportive guidelines for MF and the suitability of chlormethine as a therapeutic option in patients with MF. In addition, we present realworld experience on the use of chlormethine gel from clinics in the USA, Israel, and France with the aim of demonstrating the efficacy of chlormethine gel in routine clinical practice and outlining strategies that are being used to manage emergent cutaneous reactions.

Chlormethine Gel Versus Chlormethine Ointment for Treatment of Patients with Mycosis Fungoides: A Post-Hoc Analysis of Clinical Trial Data

“…Herein, an additional 7 months of follow-up was included for patients who enrolled in study 202 and were treated with 0.04% chlormethine gel. In clinical practice, patients often initiate treatment with chlormethine gel at a lower frequency than once daily and increase frequency of application over time, in part to avoid the development of AEs [19,20,23]. Nevertheless, our analysis on patients from pivotal studies found no association between the frequency of chlormethine gel application and the occurrence of skin-related AEs, despite once-daily application.…”

“…As the mode of action is purported to be the same for chlormethine gel and ointment formulations, the difference in time to response could be due to differences in the composition and/or drug delivery of the two formulations. The gel formulation contains the excipient Klucel™ [21] that ensures appropriate viscosity of the product and makes the gel more likely to remain at the site of administration and at the target area [20]. In-vitro permeation studies have indicated that chlormethine gel remains in the epidermal layer, with minimum levels reaching dermal tissue [22].…”

“…The CAILS scores were chosen as the main outcome for this analysis because these are considered to be more sensitive, particularly for patients with early stage MF. When initiating treatment with chlormethine gel, new lesions may seem to appear; however, these are usually subclinical MF lesions that are unmasked by chlormethine gel [20]. This mainly occurs during the first month of treatment but may affect total skin scores such as mSWAT and BSA.…”

Chlormethine Gel for Patients with Mycosis Fungoides Cutaneous T Cell Lymphoma: A Review of Efficacy and Safety in Clinical Trial and Real-World Settings

“…Cutaneous lymphoma clinics have had good experiences with CL gel for patients with MF [ 55 , 56 ], and several clinical studies have investigated CL gel treatment in a real-world setting. Here, cohort studies with more than ten patients are discussed.…”

Case Report: Primary Cardiac T-Cell Lymphoma With Complete Atrio-Ventricular Block Diagnosed by Endomyocardial Biopsy

“…Among lymphomas with cardiac involvement, the most common type of pathology is diffuse large B-cell lymphoma (58%), whereas T-cell lymphoma is quite rare (16%) ( 2 ) And 62% of patients with peripheral T-cell lymphoma present with extranodal diseases ( 7 ). T-cell lymphoma has been reported to involve the skin ( 8 ), heart ( 9 ), central nervous system (CNS) ( 10 ), intestine, and lungs ( 11 ). Also, 23% of primary cardiac lymphomas are presented with arrhythmias and AVB is even more rare at 8% ( 12 ).…”