Psoralen-ultraviolet A maintenance in mycosis fungoides: the underlying question

Vieyra-Garcia, Pablo A.; Wolf, Peter

doi:10.1111/bjd.15670

Cited by 5 publications

(6 citation statements)

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“…However, little is known about PUVA’s therapeutic mechanisms or optimal dosing, duration and frequency of treatment (2, 3, or 4 times weekly), dose escalation, and maintenance therapy . Whether PUVA maintenance therapy can prolong clinical response in MF on initial complete clearance is controversial . An online survey of 30 members of the International Society for Cutaneous Lymphoma revealed that 88% of respondents used some sort of PUVA maintenance therapy at frequencies ranging from weekly to monthly .…”

Section: Introductionmentioning

confidence: 99%

“…12,[15][16][17][18][19][20][21][22][23] Whether PUVA maintenance therapy can prolong clinical response in MF on initial complete clearance is controversial. 24,25 An online survey of 30 members of the International Society for Cutaneous Lymphoma revealed that 88% of respondents used some sort of PUVA maintenance therapy at frequencies ranging from weekly to monthly. 15 Despite this finding, the European Organisation for Research and Treatment of Cancer issued the recommendation to avoid maintenance because of unproven efficacy and safety concerns.…”

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confidence: 99%

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

et al. 2019

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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

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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

et al. 2019

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“…The therapeutic value of PUVA lies in the proapoptotic and immunomodulatory properties of psoralen when exposed to UV-A light. Although psoralen-induced crosslinking of DNA causes cell damage and inhibition of division, psoralen-induced immunomodulation also leads to an increase in regulatory T cell–suppressive activity, decreased density of Langerhans cells, and increased mast cells in the papillary dermis 21 . Additionally, psoralen's upregulatory effect on melanocyte activity has proven to be useful in the correction of hypopigmentation related to conditions such as vitiligo.…”

Section: Clinical Applicationsmentioning

confidence: 99%

“…Although psoralen-induced crosslinking of DNA causes cell damage and inhibition of division, psoralen-induced immunomodulation also leads to an increase in regulatory T cell-suppressive activity, decreased density of Langerhans cells, and increased mast cells in the papillary dermis. 21 Additionally, psoralen's upregulatory effect on melanocyte activity has proven to be useful in the correction of hypopigmentation related to conditions such as vitiligo. The success of treatment is determined by a combination of the dose of psoralen, dose of UV-A, and patient genotypic susceptibility.…”

Section: Clinical Applicationsmentioning

confidence: 99%

“…In modern times, psoralen UV-A (PUVA) therapy was introduced in 1976 to treat psoriasis, mycosis fungoides, and vitiligo. 21 The therapeutic value of PUVA lies in the proapoptotic and immunomodulatory properties of psoralen when exposed to UV-A light. Although psoralen-induced crosslinking of DNA causes cell damage and inhibition of division, psoralen-induced immunomodulation also leads to an increase in regulatory T cell-suppressive activity, decreased density of Langerhans cells, and increased mast cells in the papillary dermis.…”

Section: Clinical Applicationsmentioning

confidence: 99%

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