Journal Scan / Research · August 04, 2022 Efficacy and Safety of Topical Hypericin–Mediated PDT for Early-Stage Cutaneous T-Cell Lymphoma (Mycosis Fungoides) JAMA Dermatology

TAKE-HOME MESSAGE

• This multicenter phase III randomized clinical trial involving 169 patients with stage IA–IIA mycosis fungoides (MF), a type of cutaneous T-cell lymphoma, reported a significantly higher index lesion response rate (ILRR; defined as 50% or greater improvement in mCAILS from baseline) among patients treated with twice weekly topical synthetic hypericin 0.25% ointment–mediated photodynamic therapy (PDT) after 6 weeks than among patients treated with placebo (16% vs 4%; P = .04). The response to hypericin-mediated PDT improved with additional cycles (ILRR of 40% and 49% after cycle 2 and 3, respectively). Additionally, patch and plaque lesions showed similar response rates.

• Clinicians should consider topical synthetic hypericin–mediated PDT as a treatment option in patients with early-stage MF.

–  Ruth McTighe, MD

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 cycle, and then monthly for 6 months. Data analyses were performed on December 21, 2020.

RESULTS

The study population comprised 169 patients (mean [SD] age, 58.4 [16.0] years; 96 [57.8%] men; 120 [72.3%] White individuals) with early-stage MF/CTCL. After 6 weeks of treatment, hypericin PDT was more effective than placebo (cycle 1 ILRR, 16% vs 4%; P = .04). The ILRR increased to 40% in patients who received 2 cycles of hypericin PDT (P < .001 vs cycle 1 hypericin) and to 49% after 3 cycles (P < .001 vs cycle 1 hypericin). Significant clinical responses were observed in both patch and plaque type lesions and were similar regardless of age, sex, race, stage IA vs IB, time since diagnosis, and number of prior therapies. The most common treatment-related AEs were mild local skin (13.5%-17.3% across cycles 1-3 vs 10.5% for placebo in cycle 1) and application-site reactions (3.2%-6.9% across cycles 1-3 vs 4% for placebo in cycle 1). No drug-related serious AEs occurred.

CONCLUSION AND RELEVANCE

The findings of this randomized clinical trial indicate that synthetic hypericin PDT is effective in early-stage patch and plaque MF/CTCL and has a favorable safety profile.

JAMA Dermatology

Efficacy and Safety of Topical Hypericin Photodynamic Therapy for Early-Stage Cutaneous T-Cell Lymphoma (Mycosis Fungoides): The FLASH Phase 3 Randomized Clinical Trial

JAMA Dermatol 2022 Jul 20;[EPub Ahead of Print], EJ Kim, AR Mangold, JA DeSimone, HK Wong, L Seminario-Vidal, J Guitart, J Appel, L Geskin, E Lain, NJ Korman, N Zeitouni, N Nikbakht, K Dawes, O Akilov, J Carter, M Shinohara, TM Kuzel, W Piette, N Bhatia, A Musiek, D Pariser, YH Kim, D Elston, E Boh, M Duvic, A Huen, T Pacheco, JP Zwerner, ST Lee, M Girardi, C Querfeld, K Bohjanen, E Olsen, GS Wood, A Rumage, O Donini, A Haulenbeek, CJ Schaber, R Straube, C Pullion, AH Rook, B Poligone 

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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
Momentum Escazu: 2101-9574

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