Topical synthetic hypericin ointment 0.25% activated with visible light, a novel, nonmutagenic photodynamic therapy (PDT), was a safe and effective treatment for mycosis fungoides-cutaneous T-cell lymphoma (MF/CTCL) according to a multicenter, placebo-controlled, double-blind, phase 3 randomized clinical trial published in JAMA Dermatology.
Investigators included adults with early-stage MF/CTCL and 3 or more evaluable and discrete patch and plaque lesions in the study. They treated patients twice weekly for a 6-week cycle for up to 3 cycles. In cycle 1, patients were randomly assigned 2:1 to either receive hypericin 0.25% or placebo ointment with PDT to the 3 discrete lesions. In cycle 2, there was a crossover of patients in the placebo group to receive index-lesion treatment as well as patients in cycle 1 who had not achieved index-lesion complete clinical response. In cycle 3, which was optional, investigators conducted open-label treatment of all lesions selected by the patient and physician. A 2-week rest period after each treatment cycle allowed skin reactions to subside. Posttreatment outcomes were evaluated 6 months after the last treatment visit. The primary outcome was the effectiveness of the initial 6-week course of hypericin PDT, defined as a 50% or greater improvement in the cumulative modified Composite Assessment of Index Lesion Severity (mCAILS) score from baseline to the 8-week evaluation visit. Investigators used a logistic regression analysis with treatment and baseline total mCAILS score as independent variables to assess treatment response.
There were 166 patients included in the analysis with a mean age of 58.4 (SD, 16) years, 57.8% men, and 73.3% White. The study included patients who were both relatively naïve to treatment as well as those with multiple previous therapies.
After cycle 1, the hypericin PDT group had a significant index lesion response rate of 16% compared to 4% in the placebo group (P =.04). The index lesion response rate increased to 40% in the hypericin PDT group in both cycles 1 and 2 (P <.001). After cycle 3, the index lesion response rate increased to 49% for the hypericin PDT group (P =.05). An analysis of all patients who received hypericin PDT showed a consistent index lesion response rate of 18% after 6 weeks of hypericin PDT treatment and 40% after 12 weeks of hypericin PDT treatment. Complete clinical responses were only seen in patients who received hypericin PDT, and consolidated response rates across all individual index lesions were similar for both patch and plaque lesions. Treatment response improved with more hypericin PDT cycles (P =.01).
The most commonly reported treatment emergent adverse event was “skin reactions” (16.4% in the hypericin PDT group and 10.5% in the placebo group). Other adverse events, most of which were mild, included pruritus, hyperpigmentation, burning, pain, irritation, and application-site pain. Severe treatment-related adverse events occurred in 3 patients and resolved spontaneously, although 1 patient withdrew from the study as a result. Researchers noted that there were no clinically significant changes in any hematologic or clinical chemistry parameters.
The study was limited by incomplete information on clinical response correlating with skin condition, clinical or histologic subtypes of MF/CTCL, and presence or absence of large-cell transformation.
As hypericin PDT can be conducted using an at-home lighting unit, it could be “a valuable user-friendly option to improve access to treatment for patients who live far from a health care center and/or prefer to shift away from in-office treatments that occurred during the COVID-19 pandemic,” the study authors wrote.
Disclosure: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Kim EJ, Mangold AR, DeSimone JA, et al. 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. Published online July 20, 2022. doi:10.1001/jamadermatol.2022.2749