No cardiac effects from topical hypericin in patients with mycosis fungoides

Key takeaways:

• Patients treated with topical hypericin and phototherapy did not experience QT interval variations or heart rate changes.
• Blood samples showed hypericin did not appear to be significantly absorbed through the skin.

Topical hypericin showed efficacy in treating mycosis fungoides without significant skin absorption or significant cardiac changes, according to a study.

A naturally occurring pigment found in Hypericum plants, hypericin induces the production of reactive oxygen species that oxidize tryptophan imidazole groups in proteins and fatty acids when activated by light in the 530 nm to 600 nm wavelength, according to Carolina V. Alexander-Savino, of the department of dermatology, University of North Carolina at Chapel Hill, and colleagues.

Mycosis fungoides (MF), the most common subtype of non-Hodgkin’s lymphoma, affects the skin, blood, lymph nodes and viscera and often requires long-term therapy, the researchers added.

The prospective, open-label, single center, interventional study included nine patients (men, n = 5; white, n = 8) with MF affecting at least 10% of their body surface area.

Each patient was instructed to apply topical synthetic hypericin 0.25% (HyBryte, Soligenix) 18 to 24 hours before receiving biweekly light treatments beginning with 5 J/cm² and increasing at each visit until developing a grade 1 erythema or reaching a light intensity of 25 J/cm².

Average HyBryte doses ranged from 1.7 g to 10.3 g per patient with cumulative doses ranging from 27 g to 164.9 g.

Blood samples were collected, and ECG tests were performed at baseline and weeks 4, 6 and 8, as well as at a post-treatment follow-up at week 10.

The study’s main objective was to determine if hypericin had an effect on cardiac changes.

ECG results showed no significant clinical changes including variations to QT intervals and measured and corrected heart rate.

Baseline QT was 399 ± 24 milliseconds (range, 356-424). No patients experienced an absolute QT interval greater than 500 milliseconds or a change in QTc of more than 60 milliseconds during any of the study visits.

Average hypericin blood concentration was 0.13 ng/mL, which achieved steady state by week 4. For six of the patients, blood levels remained below detection limits through week 10.

Efficacy was evaluated using cumulative modified Composite Assessment of Index Lesion Severity (mCAILS) scores of three index lesions, the modified Severity-Weighted Assessment Tool (mSWAT) and Physician Global Assessment (PGA) at week 8.

A reduction of at least 50% in the mCAILS score was determined to be a lesion response, whereas a patient’s response was defined as having at least a 50% reduction in cumulative mCAILS score for all three index lesions.

Two patients (22%) achieved patient response, and seven (26%) of 27 treated lesions had at least 50% improvement in mCAILS score. Complete treatment response, defined as a cumulative mCAILS score of 0 at 10 weeks, was recorded in one patient (11%) and four (15%) of the 27 index lesions.

Average mCAILS scores decreased from 42 ± 16 (range, 23‐70) to 28 ± 17 (range, 0-47) at week 10.

Median improvement in mSWAT score was 29% with average scores reducing from 33 ± 30 (range, 11-98) to 26 ± 27 (range, 1-79) at week 10.

One patient (11%) experienced a 92% change from baseline in mSWAT score.

Moderate improvement of PGA was recorded at week 8 with four patients (44%) showing an improvement of at least 25% but less than 50%, two (22%) having marked improvement, defined as greater than 50%, and one (11%) experiencing at least a 90% improvement.

“This study further suggests that topical treatment with HyBryte leads to minimal serum hypericin concentration and does not correlate with significant cardiac abnormalities,” the authors wrote.