Post hoc Analysis of a Randomized, Controlled, Phase 2 Study to Assess Response Rates with Chlormethine/Mechlorethamine Gel in Patients with Stage IA-IIA Mycosis Fungoides

Abstract

Background: Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma. Patients can be treated using chlormethine gel, a skin-directed therapy developed and approved for MF. In the randomized, controlled 201 trial, chlormethine gel was found to be noninferior to equal-strength chlormethine ointment. However, there remains a need to gain more insight into outcome measures after treatment.

Objective: The aim of this study was to further investigate the potential of chlormethine gel treatment through a novel post hoc analysis of the 201 trial data (NCT00168064).

Methods: Patients were randomized to chlormethine gel or ointment; response assessments included Composite Assessment of Index Lesion Severity (CAILS) and total body surface area (BSA). In this post hoc analysis, additional subgroup response analyses were performed for stage IA/IB-IIA MF. Very good partial response (75 to <100% improvement) was included as an additional response category. Time to response and overall response trends were determined. Finally, multivariate time-to-event analyses were performed to determine whether associations were observed between treatment frequency, response, and adverse events.

Results: Response rates were significantly higher for patients with stage IA MF for CAILS (intent-to-treat [p = 0.0014] and efficacy-evaluable [EE; p = 0.0036] populations) and BSA (EE population [p = 0.0488]) treated with gel versus ointment. Time to first CAILS response and response trends were better for all-stage gel-treated patients overall. No association was seen between treatment frequency and response or occurrence of adverse events at the following visit. An association was observed between the occurrence of contact dermatitis and improved clinical response at the next visit (p = 0.0001).

Conclusion: This post hoc analysis shows that treatment with chlormethine gel may result in higher and faster response rates compared with chlormethine ointment, which confirms and expands results reported in the original analysis. The incidence of contact dermatitis may potentially be a prognostic indicator for clinical response; this needs to be confirmed in a larger population.

Keywords: Chlormethine gel; Cutaneous T-cell lymphoma; Mechlorethamine gel; Mycosis fungoides; Response rates.

Conflict of interest statement

C. Querfeld: research grant: Celgene; clinical investigator: Celgene, Trillium, miRagen, Bioniz, Kyowa Kirin; advisory board: Helsinn, miRagen, Bioniz, Trillium, Kyowa Kirin.

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.

E. Guenova: research grants: Helsinn Healthcare SA, Takeda Pharmaceutical Co., Ltd.; consultancy: Scailyte AG, Mallinckrodt Pharmaceuticals, Kyowa Hakko Kirin Co., Ltd., Novartis, Sanofi.

M. Bagot: scientific advisory board: Helsinn-Recordati, Takeda, Innate Pharma, Kyowa Kirin, Galderma.

P.L. Ortiz-Romero: advisory board: 4SC, Takeda, Actelion, Innate Pharma, Recordati Rare Diseases, Kyowa, Helsinn, miRagen; patent: PLCG1; research support: Meda (company owned by Viatris).

P. Quaglino: advisory board: 4SC, Takeda, Actelion, Innate Pharma, Recordati Rare Diseases, Kyowa, Therakos.

E. Bonizzoni: consultancy: Helsinn, Roche, Zambon, Adienne.

E. Hodak: scientific advisory board: Actelion, Helsinn, Recordati Rare Diseases, Takeda; speakers' bureau: Helsinn, Rafa, Takeda.

The Author(s). Published by S. Karger AG, Basel.

Figures

Fig. 1

Time to first occurrence of Composite Assessment of Index Lesion Severity (CAILS) response in patients in the intent-to-treat (ITT) population treated with chlormethine gel or ointment for patients with complete response (CR) (a), at least very good partial response (VGPR) (b), and at least partial response (PR) (c).

Fig. 2

Composite Assessment of Index Lesion Severity (CAILS) response trends for patients treated with chlormethine gel (dashed line) or ointment (solid line) in the intent-to-treat (a) or efficacy-evaluable populations (b). CR, complete response; VGPR, very good partial response; PR, partial response; SE, standard error.

Fig. 3

Associations between chlormethine gel application frequency and the occurrence of adverse events (a), chlormethine gel application frequency and Composite Assessment of Index Lesion Severity (CAILS) response (b), and the occurrence of dermatitis and CAILS response (c). HR, hazard ratio; CI, confidence interval.