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

Dermatology, vol. 238, pp. 347–357

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.

Authors 9

1. Christiane Querfeld

   City Of Hope National Medical Center · City of Hope

   Affiliation as printed

   City of Hope Cancer Center, Duarte, California, USA

   City of Hope Cancer Center, Duarte, CA, USA

2. Julia Jane Scarisbrick

   University of Birmingham

   Affiliation as printed

   University of Birmingham, Birmingham, United Kingdom

   University of Birmingham, Birmingham, UK

3. Chalid Assaf Aachen

   Helios Klinikum Krefeld · Universitätsklinikum Aachen

   Affiliation as printed

   Academic Teaching Hospital of the University of Aachen, Aachen, Germany

   Department of Dermatology and Venereology, Helios Klinikum Krefeld, Krefeld, Germany

4. Emmanuella Guenova

   Centre Hospitalier Universitaire Vaudois · University of Lausanne

   Affiliation as printed

   Department of Dermatology, University Hospital Lausanne, Lausanne, Switzerland

   Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland

5. Martine Bagot

   Université Paris Cité · Assistance Publique – Hôpitaux de Paris · Hôpital Saint-Louis

   Affiliation as printed

   Department of Dermatology, AP-HP, Université de Paris, Hôpital Saint-Louis, Paris, France

6. Pablo Luis Ortiz-Romero

   Universidad Complutense de Madrid · Research Institute Hospital 12 de Octubre · Hospital Universitario 12 De Octubre · Centro de Investigación Biomédica en Red de Cáncer

   Affiliation as printed

   Hospital 12 de Octubre, Institute I+12, CIBERONC, Medical School, Universidad Complutense, Madrid, Spain

7. Pietro Quaglino

   University of Turin

   Affiliation as printed

   Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy

8. Erminio Bonizzoni

   University of Milan

   Affiliation as printed

   Department of Clinical Sciences and Community, Section of Medical Statistics, Biometry and Epidemiology, University of Milan, Milan, Italy

9. Emmilia Hodak

   Tel Aviv University · Rabin Medical Center

   Affiliation as printed

   Department of Dermatology, Rabin Medical Center, Beilinson Hospital, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel