New insights on treatment utilization and outcomes in early‐stage mycosis fungoides

Abstract

Mycosis fungoides (MF) is a distinct subtype of cutaneous Tcell lymphoma (CTCL) that almost always begins as an indolent, epidermotropic extranodal lymphoma, and slowly progresses over many years. For treatment decisions, patients with MF have been divided into early stage (ES) and advanced stage (AS), based on the International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer classification. Most patients with ES-MF (Stage IA–IIA) have prolonged survival and are adequately treated with skin-directed therapies (SDTs), often requiring lifelong intermittent therapy. However, some experience stage progression and transition to AS-MF. Once patients progress to AS-MF, durable disease control is rare, and survival is significantly shortened, compared with ES-MF. MF displays a continuum of disease progression patterns and survival outcomes, as recently reported by Mourad and Gniadecki and discussed by Scarisbrick. Thus, optimal management of patients with ESMF has an impact on both risk of stage progression and survival. An urgent unmet need is the identification of biomarkers that reliably define the subset of patients with ES-MF who have higher risk of stage progression and more rapid transition from indolent to aggressive disease. In this issue of the BJD, Quaglino and colleagues present data on a large (n = 395) cohort of patients with ES-MF enrolled on the PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study, an international prospective registry, with centralized pathology review. The study’s primary objective was to measure differences in first-line treatment approaches, and to provide insight into disease-specific variables that may explain the selection of SDTs vs. systemic therapies (STs), independent of stage, with a focus on folliculotropic MF (FMF), presence of plaques, and the modified Severity Weighted Assessment Tool score. Overall, the study provides a high-quality cross-sectional survey of a large international cohort of patients with ES-MF, of the spectrum and utilization frequency of SDT and ST, and of the impact of the selected variables on risk of stage progression. The value of this study lies in the fact that centralized pathology review and prospective data collection ensure more accurate and consistent diagnosis of FMF and reliable outcome data, respectively. In this context, the study’s conclusion that the presence of plaques and FMF was significantly associated with the utilization of STs is sound, albeit predictable for FMF. However, in the absence of physician and patient survey data supporting the reasoning for treatment selection, it is impossible to determine what ‘real-life’ factors drove that selection, especially considering that the cost, access, toxicity and dosing schedules for STs vary considerably. Furthermore, the observation that SDTs were associated with better outcomes than STs in this cohort requires confirmation, because the subset of patients with ES-MF who received ST was quite small (11 1%), and because the median follow-up (1 3 years) was short. It also should be noted that this difference in outcomes was much greater in stage IB (overall response rate of 48% for ST vs. 72% for SDT), where a wide range for the extent of skin involvement (10–80% body surface area) may not distinguish well the burden of skin disease for each treatment group. In summary, Quaglino and colleagues make an important contribution to our understanding of the global treatment landscape and outcome of ES-MF, but much more work remains to be done to take us closer to biomarker-guided therapy for these patients. A large, prospective, highly curated patient cohort like the one being enrolled in the PROCLIPI study is ideal for the identification of high-risk genetic subsets of ES-MF and for validation of tumour clone frequency measurement in lesional skin via high-throughput sequencing of the T-cell receptor beta, which appears to be a promising predictive biomarker for disease progression and survival in ES-MF.