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Evaluation of Low-Dose, Low-Frequency Oral Psoralen-UV-A Treatment With or Without Maintenance on Early-Stage Mycosis Fungoides: A Randomized Clinical Trial.
JAMA Dermatol. 2019 05 01; 155(5):538-547.JD

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.

Authors+Show Affiliations

Research Unit for Photodermatology, Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria.Research Unit for Photodermatology, Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria.Department of Dermatology, Medical University of Vienna, Vienna, Austria.Department of Dermatology, Paracelsus Medical University, Salzburg, Austria.Department of Dermatology, Hietzing Hospital, Vienna, Austria.Department of Dermatology and Venerology, Medical University of Innsbruck, Innsbruck, Austria.Department of Dermatology, Medical University of Vienna, Vienna, Austria.Department of Dermatology, Paracelsus Medical University, Salzburg, Austria.Department of Dermatology, Hietzing Hospital, Vienna, Austria.Research Unit for Photodermatology, Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria.Research Unit for Photodermatology, Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria.Research Unit for Photodermatology, Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria.Research Unit for Photodermatology, Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria.Institute of Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria.Research Unit for Photodermatology, Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria.Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.Research Unit for Photodermatology, Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria.

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30892603

Citation

Vieyra-Garcia, Pablo, et al. "Evaluation of Low-Dose, Low-Frequency Oral Psoralen-UV-A Treatment With or Without Maintenance On Early-Stage Mycosis Fungoides: a Randomized Clinical Trial." JAMA Dermatology, vol. 155, no. 5, 2019, pp. 538-547.
Vieyra-Garcia P, Fink-Puches R, Porkert S, et al. Evaluation of Low-Dose, Low-Frequency Oral Psoralen-UV-A Treatment With or Without Maintenance on Early-Stage Mycosis Fungoides: A Randomized Clinical Trial. JAMA Dermatol. 2019;155(5):538-547.
Vieyra-Garcia, P., Fink-Puches, R., Porkert, S., Lang, R., Pöchlauer, S., Ratzinger, G., Tanew, A., Selhofer, S., Paul-Gunther, S., Hofer, A., Gruber-Wackernagel, A., Legat, F., Patra, V., Quehenberger, F., Cerroni, L., Clark, R., & Wolf, P. (2019). Evaluation of Low-Dose, Low-Frequency Oral Psoralen-UV-A Treatment With or Without Maintenance on Early-Stage Mycosis Fungoides: A Randomized Clinical Trial. JAMA Dermatology, 155(5), 538-547. https://doi.org/10.1001/jamadermatol.2018.5905
Vieyra-Garcia P, et al. Evaluation of Low-Dose, Low-Frequency Oral Psoralen-UV-A Treatment With or Without Maintenance On Early-Stage Mycosis Fungoides: a Randomized Clinical Trial. JAMA Dermatol. 2019 05 1;155(5):538-547. PubMed PMID: 30892603.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluation of Low-Dose, Low-Frequency Oral Psoralen-UV-A Treatment With or Without Maintenance on Early-Stage Mycosis Fungoides: A Randomized Clinical Trial. AU - Vieyra-Garcia,Pablo, AU - Fink-Puches,Regina, AU - Porkert,Stefanie, AU - Lang,Roland, AU - Pöchlauer,Sophie, AU - Ratzinger,Gudrun, AU - Tanew,Adrian, AU - Selhofer,Sylvia, AU - Paul-Gunther,Sator, AU - Hofer,Angelika, AU - Gruber-Wackernagel,Alexandra, AU - Legat,Franz, AU - Patra,Vijaykumar, AU - Quehenberger,Franz, AU - Cerroni,Lorenzo, AU - Clark,Rachael, AU - Wolf,Peter, PY - 2019/3/21/pubmed PY - 2020/2/12/medline PY - 2019/3/21/entrez SP - 538 EP - 547 JF - JAMA dermatology JO - JAMA Dermatol VL - 155 IS - 5 N2 - 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. SN - 2168-6084 UR - https://www.unboundmedicine.com/medline/citation/30892603/Evaluation_of_Low_Dose_Low_Frequency_Oral_Psoralen_UV_A_Treatment_With_or_Without_Maintenance_on_Early_Stage_Mycosis_Fungoides:_A_Randomized_Clinical_Trial_ DB - PRIME DP - Unbound Medicine ER -