Mycosis fungoides (MF) is a chronic malignant condition characterized by a proliferation of clonal T helper cells in the skin. MF remains difficult to treat despite being the most common cutaneous T cell lymphoma. The disease is often refractory, with existing treatments providing only a short duration of clinical response [1]. A 2020 Cochrane review, “Interventions for mycosis fungoides,” provides a comprehensive review of evidence from 20 randomized clinical trials of local and systemic interventions for Alibert-Bazin–type MF (N=1369) [2]. Interventions evaluated in this review included topicals, intralesional therapies, phototherapy, total skin electron beam irradiation, radiotherapy, chemotherapy, extracorporeal photochemotherapy (ECP), biologics, and combination therapies.

The authors aimed to assess the efficacy and safety of interventions for MF using two primary outcome measures: health-related quality of life (HRQoL) and adverse events (AEs). Secondary outcomes included complete response (CR) and objective response rate (ORR). A CR was defined as the complete disappearance of all clinical evidence of disease. The ORR was defined as the proportion of patients with a CR or partial response, meaning the regression of measurable disease of at least 50% in the T, N, M, and B categories. Key outcomes are reported in Table 1. HRQoL was only reported in two studies that could not be analyzed together as it was divided by responder versus nonresponder rather than by treatment group. Common AEs ranged from mild symptoms to severe events. Overall, the evidence indicated that the more aggressive therapies (systemic chemotherapy and combination therapies) resulted in more severe AEs. From all therapies, the CR ranged from 0% to 83% (median 31%), and the ORR ranged from 0% to 88% (median 47%).

Data analysis of the five trials assessing the use of psoralen plus UV-A (PUVA) contributed to the key findings of this review, as it is first-line therapy for early-stage MF and is often used as adjunctive treatment in advanced stages. The authors found no evidence to support the addition of bexarotene or intralesional interferon-α (IFN-α) to PUVA when compared to PUVA alone. Separately, they noted that PUVA combined with IFN-α may lead to a higher CR when compared to IFN-α combined with acitretin. The authors did not find evidence to refute the recommendation of PUVA as a first-line treatment. There was insufficient evidence for adjunctive or alternative therapies such as acitretin or ECP to treat MF.

Using GRADE (Grading of Recommendations, Assessment, Development and Evaluations) criteria, the authors report a lack of high-certainty evidence to guide MF treatment. Many trials included in the review were either inadequate in methodological quality, heterogenous in design, or had insufficient sample sizes. Reported outcomes varied across studies, prohibiting conclusive assessments of the safety, efficacy, and HRQoL impact of these interventions.

Although MF, particularly early stage, generally portends a favorable prognosis, a recent cause of death analysis combining all stages of the disease revealed that patients with MF are most likely to die of the disease [3]. The incidence of MF has been increasing over the past 50 years without concurrent improvement in evidence-based treatment options [3]. In line with most MF treatment guidelines, this review supports PUVA as a major intervention used in MF—a therapy that may be limited by a maximum lifetime dose after which increased risk for melanoma and squamous cell carcinoma become a concern [4]. Thus, future efforts should be directed toward high-quality studies with patient-reported outcomes, safety, and efficacy of alternative MF interventions [5].