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Summary Background The PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study is a prospective analysis of an international database. Here we examine front‐line treatments and quality of life (QoL) in patients with newly diagnosed mycosis fungoides (MF). Objectives To identify (i) differences in first‐line approaches according to tumour‐nodes‐metastasis‐blood (TNMB) staging; (ii) parameters related to a first‐line systemic approach and (iii) response rates and QoL measures. Methods In total, 395 newly diagnosed patients with early‐stage MF (stage IA–IIA) were recruited from 41 centres in 17 countries between 1 January 2015 and 31 December 2018 following central clinicopathological review. Results The most common first‐line therapy was skin‐directed therapy (SDT) (322 cases, 81·5%), while a smaller percentage (44 cases, 11·1%) received systemic therapy. Expectant observation was used in 7·3%. In univariate analysis, the use of systemic therapy was significantly associated with higher clinical stage (IA, 6%; IB, 14%; IIA, 20%; IA–IB vs. IIA, P < 0·001), presence of plaques (T1a/T2a, 5%; T1b/T2b, 17%; P < 0·001), higher modified Severity Weighted Assessment Tool (> 10, 15%; ≤ 10, 7%; P = 0·01) and folliculotropic MF (FMF) (24% vs. 12%, P = 0·001). Multivariate analysis demonstrated significant associations with the presence of plaques (T1b/T2b vs. T1a/T2a, odds ratio 3·07) and FMF (odds ratio 2·83). The overall response rate (ORR) to first‐line SDT was 73%, while the ORR to first‐line systemic treatments was lower (57%) (P = 0·027). Health‐related QoL improved significantly both in patients with responsive disease and in those with stable disease. Conclusions Disease characteristics such as presence of plaques and FMF influence physician treatment choices, and SDT was superior to systemic therapy even in patients with such disease characteristics. Consequently, future treatment guidelines for early‐stage MF need to address these issues.

Data on the treatment of early folliculotropic mycosis fungoides, a recently defined clinicopathological subgroup of folliculotropic mycosis fungoides with an indolent course, is limited. Treatment outcomes were studied in a retrospective cohort of 47 adults with early folliculotropic mycosis fungoides, with a focus on psoralen plus ultraviolet A (PUVA) monotherapy, including dosimetric data, and the findings were compared with data for PUVA in 18 adults with early-classic mycosis fungoides. PUVA was given to 27 patients with early folliculotropic mycosis fungoides: 70% achieved complete response and 26% partial response. Significantly more treatments were needed to achieve complete response in stage IB compared with stage IA. There was no significant difference in the complete response rate from classic plaque-stage disease, although the early folliculotropic mycosis fungoides group required more treatments to achieve complete response, and a higher cumulative dose of UVA. Thus, PUVA is an effective treatment for early folliculotropic mycosis fungoides. Its complete response rate might be equal to early-classic mycosis fungoides; however, a longer induction phase is needed to achieve complete response.

Summary Background Literature regarding exosomes as mediators in intercellular communication to promote progression in mycosis fungoides (MF) is lacking. Objectives To characterize MF‐derived exosomes and their involvement in the disease. Methods Exosomes were isolated by ultracentrifugation from cutaneous T‐cell lymphoma (CTCL) cell lines, and from plasma of patients with MF and controls (healthy individuals). Exosomes were confirmed by electron microscopy, NanoSight and CD81 staining. Cell‐line exosomes were profiled for microRNA array. Exosomal microRNA (exomiRNA) expression and uptake, and plasma‐cell‐free microRNA (cfmiRNA) were analysed by reverse‐transcriptase quantitative polymerase chain reaction. Exosome uptake was monitored by fluorescent labelling and CD81 immunostaining. Migration was analysed by transwell migration assay. Results MyLa‐ and MJ‐derived exosomes had a distinctive microRNA signature with abundant microRNA (miR)‐155 and miR‐1246. Both microRNAs were delivered into target cells, but only exomiR‐155 was tested, demonstrating a migratory effect on target cells. Plasma levels of cfmiR‐1246 were significantly highest in combined plaque/tumour MF, followed by patch MF, and were lowest in controls (plaque/tumour > patch > healthy), while cfmiR‐155 was upregulated only in plaque/tumour MF vs. controls. Specifically, exomiR‐1246 (and not exomiR‐155) was higher in plasma of plaque/tumour MF than in healthy controls. Plasma exosomes from MF but not from controls increased cell migration. Conclusions Our findings show that MF‐derived exosomes promote cell motility and are enriched with miR‐155, a well‐known microRNA in MF, and miR‐1246, not previously reported in MF. Based on their plasma expression we suggest that they may serve as potential biomarkers for tumour burden.