Evaluation of Low-Dose, Low-Frequency Oral Psoralen–UV-A Treatment With or Without Maintenance on Early-Stage Mycosis Fungoides

Abstract

Psoralen-UV-A (PUVA) photochemotherapy is standard first-line treatment for skin-limited, early-stage mycosis fungoides capable of producing high initial complete response (CR) rates. However, much remains unknown about PUVA's therapeutic mechanisms, optimal duration and frequency of treatment, dose escalation, or use as maintenance therapy. OBJECTIVES To evaluate low-dose, low-frequency PUVA, and whether maintenance treatment extends disease-free remission in patients with mycosis fungoides. DESIGN, SETTING, AND PARTICIPANTS This prospective randomized clinical trial with defined PUVA dosing regimen was carried out in 5 centers (Graz, Vienna, Hietzing, Innsbruck, and Salzburg) across Austria. Patients with stage IA to IIA mycosis fungoides (n = 27) were enrolled in the study beginning March 13, 2013, with the last patient enrolled March 21, 2016. These patients were treated with oral 8-methoxypsoralen followed by UV-A exposure 2 times per week for 12 to 24 weeks until CR. Patients with CR were randomized to PUVA maintenance for 9 months (14 total exposures) or no maintenance. The study was conducted from April 27, 2012, to July 27, 2018. Data analysis of the primary end point was of the intention-to-treat population, and the secondary end point analysis was of the evaluable population. MAIN OUTCOMES AND MEASURES Efficacy of the PUVA regimen was determined by the rate of CR as defined by a modified severity-weighted assessment tool (mSWAT) score reduction to 0. Levels of proinflammatory molecules in serum and histologic features and percentage of clonal T cells in skin were assessed to search for biomarkers of clinical response. RESULTS In 27 patients with mycosis fungoides, 19 (70%) were male with mean (range) age 61 (30-80) years. At baseline, patients with CR had a mean (range) mSWAT score of 18.6 (1-66) compared with 16.8 (3-46) in patients with partial response. The 12-to 24-week PUVA induction regimen reduced the mSWAT score in all patients and led to CR in 19 (70%) of 27 patients and a low mean cumulative UV-A dose of 78.5 J/cm 2. The subsequent standardized 9-month PUVA maintenance phase prolonged median (range) disease-free remission from 4 (1-20) months to 15 (1-54) months (P = .02). High density of histologic infiltrate and high percentage of clonal TCR sequences in skin biopsy specimens at baseline were inversely associated with therapeutic response. No severe adverse effects were seen during the PUVA induction or maintenance phase. CONCLUSIONS AND RELEVANCE This proof-of-concept study identifies potential biomarkers for therapeutic response to PUVA in mycosis fungoides; it also demonstrates that low-dose, low-frequency PUVA appears to be highly effective, and maintenance treatment may extend disease-free remission. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01686594

Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+ T cells in cutaneous T-cell lymphoma

“…Given the prevalence of S. aureus colonisation in CTCL skin lesions and their ubiquitous production of alpha-toxin, this may explain why a reduction of bacterial infections by psoralen and ultraviolet A (PUVA) and local or systemic antibiotic treatment clinically improves CTCL. 8,9,24 Indeed, it is possible that the efficiency of PUVA treatment may rely on its anti-bacterial effect and an interplay between skin resident dendritic and/or malignant cells with non-malignant T cells 12,13,25,26 and its modulation by alpha-toxin.…”

Skin colonization by circulating neoplastic clones in cutaneous T-cell lymphoma

“…Ethical approval was obtained from the Health Research Ethics Board of Alberta, Cancer Committee HREBA.CC-16-0820-REN1. After informed consent, 4mm punch skin biopsies were collected from patients and embedded in optimal cutting temperature (OCT) medium stored at -80 o C. 10…”

“…by electron beam radiation therapy or psoralen ultraviolet A therapy [PUVA]) almost never results in a cure but only in a short-term responses. [7][8][9][10] Third, cells sharing molecular characteristics of malignant T-cells in MF have been found in the bone marrow of the patients years before the emergence of skin lesions of the disease 11 and CTCL can be transmitted via the bone marrow transplant from asymptomatic donors 12,13 . Fourth, MF may share the common precursor with other lymphomas (e.g.…”

Enhanced topical psoralen–ultraviolet A therapy via targeting to hair follicles

“…Dear Editor , Renewed interest in psoralen–ultraviolet A (PUVA) therapy driven by impressive recent results in this field has encouraged researchers and clinicians to shift momentum back in its favour . While administration of low cumulative UVA doses minimizes the negative risks, the search for efficient modalities decreasing the frequency of sessions may help this therapeutic option .…”