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May 10, 2021
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Hypericin photodynamic therapy effective for short-term mycosis fungoides treatment

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Treatment with synthetic hypericin produced significant index lesion response in patients with early-stage mycosis fungoides cutaneous T-cell lymphoma, according to a study presented at AAD VMX 2021.

Visible light of 500 nm to 650 nm activates the synthetic hypericin to penetrate deeper into the skin than ultraviolet radiation therapy.

Ellen J. Kim, MD, professor of dermatology at the University of Pennsylvania, said during the presentation that there is a lack of randomized control trials comparing mycosis fungoides cutaneous T-cell lymphoma (MF-CTCL) topical agents.

“Current skin-directed therapies for CTCL have various short-term and/or long-term adverse effects that may limit use. All CTCL physicians agree we very much need additional safe, effective therapies for patients,” she said.

The study was the largest multicenter, randomized, double-blind, placebo-controlled, skin-directed therapy conducted for MF-CTCL to date, according to Kim. It included 166 patients with MF-CTCL for a median of 2 to 3 years, randomly selected into a treatment group of 116 participants and placebo group of 50 participants.

There were three cycles of 6-week treatments in the study. The first cycle involved selectingthree index lesions for treatment twice weekly. For those receiving the hypericin treatment, participants’ skin remained covered for 18 to 24 hours and then exposed to visible light starting at 5 J/cm². The treatment exposure increased by 1 J/cm² every visit until light erythema or a maximum dose of 12 J/cm² was reached. In cycle two, all participants, including those in the placebo arm, had their index lesions treated with hypericin. The optional third cycle included treatment of all lesions.

The primary outcome was a 50% or greater decrease in modified Composite Assessment of Index Lesion Severity score assessed 2 weeks off of therapy.

After cycle one with 6 weeks of therapy and 2 weeks off, there was a 16% index lesion response rate in the hypericin group compared with 4% in the placebo group (P = .0416). In cycle two, in patients with two cycles of treatment, index response rate increased to 40%. In the optional cycle three, which 78 patients participated in, those who received all three cycles of hypericin had a 49% response rate at 24 weeks.

No considerable difference in safety between the placebo group and the hypericin group presented in cycle one. Mild to moderate local skin application site adverse events occurred in 16% of participants.

“While longer follow-up is needed, hypericin-based photodynamic therapy based on its non-mutagenic mechanism of action should not be associated with long-term actinic skin damage or increased risk of skin cancer, which would be very important for CTCL patients who require chronic long-term therapy and would be a definite advantage over traditional ultraviolet light-based phototherapy,” Kim said.