The PROVe Study: US Real-World Experience with Chlormethine/Mechlorethamine Gel in Combination with Other Therapies for Patients with Mycosis Fungoides Cutaneous T-Cell Lymphoma

Abstract

Background Chlormethine/mechlorethamine gel is a skin-directed therapy for patients with mycosis fungoides cutaneous T-cell lymphoma. Currently, real-world data on chlormethine gel are lacking. Objective Our objective was to analyze the effect of chlormethine gel in combination with other therapies on efficacy, safety, and health-related quality of life in a real-world setting. Methods This prospective, observational study enrolled adult patients actively using chlormethine gel. Patients were monitored for up to 2 years during standard-of-care clinic visits. No specific visit schedules or clinical assessments, with the exception of patient-completed questionnaires, were mandated because of the expected variability in practice patterns. The primary efficacy endpoint was the proportion of patients with stage IA-IB disease receiving chlormethine + topical corticosteroids + other with ≥ 50% decrease in body surface area from baseline to 12 months. Response was assessed at each visit using by-time analysis, which investigates the trend to treatment response and allows assessment of response over time. Health-related quality of life was assessed with the Skindex-29 questionnaire. Results In total, 298 patients were monitored. At 12 months post-treatment initiation, 44.4% (chlormethine + topical corticosteroids + other) and 45.1% (patients receiving chlormethine + other treatment) of efficacy-evaluable patients were responders. By-time analysis demonstrated that peak response occurred (chlormethine + other; 66.7%) at 18 months. There was a significant correlation between responder status and lower post-baseline Skindex-29 scores. Conclusions This real-world study confirmed that chlormethine gel is an important therapeutic option for patients with mycosis fungoides and contributes to reducing the severity of skin lesions and improving health-related quality of life.

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

“…Efforts are ongoing to gain a more in-depth understanding of the utility of chlormethine gel in patients with MF and the nature of the emergent skin reactions. The PROVe trial found that chlormethine gel is an effective treatment across all disease stages [ 45 ]. No chlormethine gel-related serious AEs occurred in the study, and the reported emergent skin-related AEs were manageable and less prevalent than in the pivotal clinical trial [ 15 ], possibly because of frequent dose adjustments and the co-administration of corticosteroids, which reflect the real-world experience reported herein.…”

“…A peak response occurred at 18 months for patients with stage IA and IB disease in the chlormethine plus other treatment group (67%). Overall, 28% of patients experienced a treatment-related AE; the most common skin-related AEs deemed to be therapy related were dermatitis (12%), pruritus (7%), skin irritation (7%), and erythema (4%) [ 45 ].…”

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

“…The PROVe study (a PROspective, observational study assessing outcomes, adverse events [AEs], treatment patterns, and QOL in patients diagnosed with MF and treated with Valchlor and other therapies) examined the use of CL gel in clinical practices across the USA over a 2-year period [ 38 , 57 ]. In total, 298 patients were treated with CL gel.…”

Cutaneous T‐cell lymphomas: 2021 update on diagnosis, risk‐stratification, and management

“…(mechlorethamine [USAN]) 0.02% gel. 117 In a phase 2 trial, patients with stage IA-IIA MF were treated with 0.02% gel daily for up to 12 months. A response was observed in 58.5% of patients, with 13.8% achieving a complete response.…”

“…In an uncontrolled prospective study, topical clobetasol propionate was used in 85% of patients with stage 1 A/B disease, had an overall response rate of 94%, and is associated with minimal to no toxicity 115,116. An alternative topical medication is chlormethine (INN) (mechlorethamine [USAN]) 0.02% gel 117. In a phase 2 trial, patients with stage IA-IIA MF were treated with 0.02% gel daily for up to 12 months.…”