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

Abstract

Background: Chlormethine gel was approved for treatment of mycosis fungoides, the most common cutaneous T-cell lymphoma, on the basis of results from study 201 and study 202. A post-hoc analysis of study 201 found interesting trends regarding improved efficacy of chlormethine gel vs ointment and noted a potential association between dermatitis and clinical response.

Objective: To expand these results by performing a post-hoc analysis of study 202.

Patients and methods: Patients received chlormethine gel or ointment during study 201 (12 months) and higher-concentration chlormethine gel during study 202 (7-month extension). Response was assessed using Composite Assessment of Index Lesion Severity (CAILS). Associations between treatment frequency, response, and skin-related adverse events (AEs) were assessed using multivariate time-to-event analyses. Time-to-response and repeated measures analyses were compared between patients who only used chlormethine gel and those who switched from ointment to gel.

Results: No associations were seen between treatment frequency and improved skin response (CAILS) or AE occurrence within the 201/202 study populations. However, an association was observed specifically between contact dermatitis and improved CAILS response at the next visit (p < 0.0001). Patients who used chlormethine gel during both studies had a significantly (p < 0.05) shorter time to response and higher overall response rates than patients who initiated treatment with ointment.

Conclusions: This post-hoc analysis shows that patients who initiated treatment using chlormethine gel had faster and higher responses compared with patients who initially used chlormethine ointment for 12 months. The development of contact dermatitis may be a potential prognostic factor for response.

Trial registration numbers and dates of registration: Study 201: NCT00168064, September 14, 2002; Study 202: NCT00535470, September 26, 2007.

Conflict of interest statement

C. Querfeld: Research grant: Celgene; clinical investigator: Helsinn, Celgene, Trillium, miRagen, Bioniz, Kyowa Kirin; advisory board: Helsinn, miRagen, Bioniz, Almirall, Trillium, Kyowa Kirin, Stemline Therapeutics. J.J. Scarisbrick: Consultancy: Takeda, Helsinn, Recordati, 4SC, Kyowa, Mallinckrodt, miRagen; research grant: Kyowa. C. Assaf: Advisory board: 4SC, Takeda, Helsinn, Innate Pharma, Recordati Rare Diseases, Kyowa. Y.H. Kim: Steering committee and research funding: Eisai; research funding: Forty Seven; advisory board member: Seattle Genetics; steering committee member, advisory board, and research funding: Kyowa Hakko Kirin; research funding: Portola, Horizon; research funding: Soligenix; steering committee, advisory board, research funding: Innate; research funding: Elorac; advisory board and research funding: Galderma; steering committee and research funding: Corvus; research funding Trillium. J. Guitart: Research support: Galderma, Soligenix; scientific advisory board: Kyowa Kirin. P. Quaglino: Advisory board: 4SC, Takeda, Actelion, Innate Pharma, Helsinn, Recordati Rare Diseases, Kyowa, Therakos. E. Hodak: Scientific advisory board: Actelion, Helsinn, Recordati Rare Diseases, Takeda; speakers’ bureau: Helsinn, Rafa, Takeda.

© 2022. The Author(s).

Figures

Fig. 1

Patient flow during study 201 and study 202

Fig. 2

Association between the occurrence of contact dermatitis and an improved CAILS response at the next visit. For these analyses, data from patients included in the safety population of the study 201 chlormethine gel arm (n = 128) and from all patients in study 202 were included. CI confidence interval, HR hazard ratio

Fig. 3

Kaplan-Meier curves showing the time to first Composite Assessment of Index Lesion Severity (CAILS) response for patients treated with chlormethine gel during both study 201 and 202, and patients treated with chlormethine ointment during study 201 and chlormethine gel during study 202, with complete response (CR), at least very good partial response (VGPR), and at least partial response (PR) when including a all patients enrolled in the intent-to-treat population of study 201 and 202 or b including only those patients who were enrolled in study 202

Fig. 4

Repeated measures analysis for patients treated with chlormethine gel during both study 201 and 202 and patients treated with chlormethine ointment during study 201 and chlormethine gel during study 202 with at least partial response (PR). SE standard error