Dataset Information

Evaluation of Low-Dose, Low-Frequency Oral Psoralen-UV-A Treatment With or Without Maintenance on Early-Stage Mycosis Fungoides: A Randomized Clinical Trial.

ABSTRACT:

Importance

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/cm2. 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.

SUBMITTER: Vieyra-Garcia P

PROVIDER: S-EPMC6506892 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Importance:Phototherapy is one of the mainstays of treatment for early mycosis fungoides (MF). The most common modalities are psoralen-UV-A (PUVA) and narrowband UV-B (NBUVB). Objective:To compare the efficacy and adverse effects of PUVA vs NBUVB in early-stage MF. Data Sources:A systematic review was performed by searching Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Ovid Medline, PubMed, Cochrane Library, American College of Physicians ACP Journal Club, and Database of Abstracts of Review of Effectiveness from inception to March 30, 2018. UV A, PUVA, mycosis fungoides, Sézary syndrome, cutaneous T-cell lymphoma, UV B, and UVB were used as either key words or MeSH terms. Study Selection:Studies of cohorts with histologically confirmed early-stage MF, defined as stages IA, IB, and IIA, that compared PUVA vs NBUVB, had at least 10 patients in each comparator group, and reported outcomes of response to therapy. Exclusion criteria were studies with patients with stage IIB or higher MF, pediatric patients, fewer than 10 in each comparator group, noncomparative studies, case reports, and abstract studies. Data Extraction and Synthesis:The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed. Data were pooled using a random-effects model with odds ratio (OR) as effect size. Main Outcomes and Measures:Main outcomes were complete response rate, partial response rate, disease recurrence, and adverse effects, including erythema, nausea, pruritus, phototoxic effects, dyspepsia, and pain. Results:Seven studies were included with a total of 778 patients (405 of 724 [55.9%] men; mean age, 52 years); 527 were treated with PUVA and 251 with NBUVB. Most of the included studies were of poor to moderate quality. Any response was found in 479 of the 527 (90.9%) patients treated with PUVA vs 220 of 251 (87.6%) treated with NBUVB (OR, 1.40; 95% CI, 0.84-2.34; P = .20). Complete response was found in 389 of 527 (73.8%) patients who received PUVA vs 156 of 251 (62.2%) who received NBUVB, which was statistically significant (OR, 1.68; 95% CI, 1.02-2.76; P = .04). Partial response was similar (90 of 501 [18.0%] vs 64 of 233 [27.5%]; OR, 0.58; 95% CI, 0.33-1.04; P = .07). No significant difference was found between PUVA and NBUVB in terms of adverse effects of erythema (38 of 527 [7.2%] vs 17 of 251 [6.7%]; P = .54), nausea (10 of 527 [1.9%] vs 3 of 251 [1.2%]; P = .72), pruritus (2 of 527 [0.4%] vs 4 of 251 [1.7%]; P = .26), phototoxic effects (7 of 527 [1.4%] vs 2 of 251 [0.9%]; P = .72), dyspepsia (6 of 527 [1.2%] vs 0 of 251 [0%]; P = .59), or pain (0 of 527 [0%] vs 2 of 251 [0.9%]; P = .50). Conclusions and Relevance:The findings suggest that PUVA is a potential alternative to NBUVB in the management of early-stage MF. These findings have implications for clinicians involved in the management of early-stage MF.