Efficacy and Safety of Topical Hypericin Photodynamic Therapy for Early-Stage Cutaneous T-Cell Lymphoma (Mycosis Fungoides)

作者：Ellen J. Kim, Aaron R. Mangold, Jennifer DeSimone, Henry K. Wong, Lucia Seminario‐Vidal, Joan Guitart, James Appel, Larisa J. Geskin, Edward Lain, Neil J. Korman, Nathalie C. Zeitouni, Neda Nikbakht, Kenneth Dawes, Oleg E. Akilov, Joi Carter, Michi M. Shinohara, Timothy Michael Kuzel, Warren W. Piette, Neal D Bhatia, Amy C. M. Musiek, David M. Pariser, Youn H. Kim, Dirk M. Elston, Erin Boh, Madeleine Duvic, Auris Huen, Theresa R. Pacheco, Jeffrey P. Zwerner, Seung‐Tae Lee, Michael Girardi, Christiane Querfeld, Kimberly A. Bohjanen, Elise A. Olsen, Gary S. Wood, Adam Rumage, Oreola Donini, Andrea Haulenbeek, Christopher J. Schaber, Richard Straube, Christopher Pullion, Alain H. Rook, Brian Poligone · 发表于：JAMA Dermatology · 年份：2022 · DOI：10.1001/jamadermatol.2022.2749 · 被引用次数：55 · 研究领域：Cutaneous lymphoproliferative disorders research、Photodynamic Therapy Research Studies、Nonmelanoma Skin Cancer Studies

Importance: Given that mycosis fungoides-cutaneous T-cell lymphoma (MF/CTCL) is chronic, there is a need for additional therapies with minimal short- and long-term adverse effects. Topical synthetic hypericin ointment, 0.25%, activated with visible light is a novel, nonmutagenic photodynamic therapy (PDT). Objectives: To determine the efficacy and safety of topical synthetic hypericin ointment, 0.25%, activated with visible light as a nonmutagenic PDT in early-stage MF/CTCL. Design, Settings, and Participants: This was a multicenter, placebo-controlled, double-blinded, phase 3 randomized clinical trial (FLASH study) conducted from December 2015 to November 2020 at 39 academic and community-based US medical centers. Participants were adults (≥18 years) with early-stage (IA-IIA) MF/CTCL. Interventions: In cycle 1, patients were randomized 2:1 to receive hypericin or placebo to 3 index lesions twice weekly for 6 weeks. In cycle 2, all patients received the active drug for 6 weeks to index lesions. In cycle 3 (optional), both index and additional lesions received active drug for 6 weeks. Main Outcomes and Measures: The primary end point was index lesion response rate (ILRR), defined as 50% or greater improvement in modified Composite Assessment of Index Lesion Severity (mCAILS) score from baseline after 6 weeks of therapy for cycle 1. For cycles 2 and 3, open label response rates were secondary end points. Adverse events (AEs) were assessed at each treatment visit, after each cyc...