O11 A patchy prognosis: identification of prognostic factors associated with progression in early-stage mycosis fungoides and first-line treatment selection

Abstract Advanced mycosis fungoides (MF) and Sézary syndrome typically have a poor prognosis of < 5 years’ survival. In addition, over 25% of patients with early-stage MF progress to having advanced disease. The current European Organisation for Research and Treatment of Cancer consensus for treatment of early-stage MF recommends systemic immunotherapies if patients are refractory to skin-directed therapy. Systemic treatments are listed in no specific order, and selection varies between centres. Developing a prognostic index involving early-stage MF will identify patients with progression, therefore poor outcomes, and allow better treatment choices and improve survival. The Cutaneous Lymphoma International Consortium (CLIC) launched the PROCLIPI (PROspective Cutaneous Lymphoma International Prognostic Index) study in 2015 at over 50 international expert centres for MF and Sézary syndrome, prospectively collecting predefined datasets to determine a prognostic index. Overall, 2172 patients were recruited at 52 international sites, of whom 1622 (74.7%) had early-stage disease. Patients with early-stage disease (IA–IIA) presented at a median age of 58 years (interquartile range 44–69). Factors associated with progression to advanced disease included presence of cutaneous plaques (P < 0.001), nodal involvement (Nx–N2) (P < 0.001), age > 60 years (P = 0.016) and large cell transformation in skin (P < 0.001). The 5-year overall survival rates for patients with early-stage disease were 94.3% for IA, 84.3% for IB and 74.3% for IIA, with a significant difference between stages (P < 0.001). A further analysis of 397 patients with early-stage MF, who had been centrally reviewed for diagnostic clinical images, pathology and immunohistochemistry, displayed vast heterogeneity in first-line treatment approaches. The first-line treatment choices were categorized into skin-directed therapies (84%), systemic therapy (11%) and expectant management (7%). When stratified by staging there was a significant difference (P < 0.001) between patients with stage IA–IB and IIA MF receiving systemic treatment first line. The overall response rate for skin-directed therapies was 73.9%, compared with 59% for systemic treatments given as first-line treatments. Two areas were identified as having a higher clinical need due to lower levels of response to first-line treatment: these were patients with FMF (45% no response vs. 31% in classic MF) and patients with stage IIA disease (57% no response vs. 35% in stage IB and 25% in IA). In conclusion, early-stage MF is typically reported as a low-grade lymphoma; however, data from PROCLIPI show 5-year survival rates of just 84.3% in stage IB and 74.3% in stage IIA. Coupled with a median age of diagnosis of 58 years, there is a marked reduction in life expectancy for many patients with early-stage MF, with approximately one in five patients with stage IB/IIA surviving < 5 years from diagnosis. The results confirm the heterogeneity in treatment approaches and that there is an urgent clinical need to identify patients with poor prognostic markers in early-stage disease for better treatment selection to improve clinical outcomes and survival.