Introduction: Therapeutic approaches for patients (pts) with essential thrombocythaemia (ET) are heterogeneous and the optimal treatment strategy to achieve reduction in risks of thrombosis, hemorrhage and transformation to myelofibrosis or leukemia in the long term remains unclear. Standard first-line therapy choice for ET, supported by data from randomized trials, remains low-dose aspirin with hydroxycarbamide (HC), but the role of interferon (IFN) is increasingly highlighted. Recently conducted randomised studies provide short term information but at present we rely upon long term well annotated patient cohorts to guide appropriate therapy.Objective: Descriptive, single-center, retrospective study of ET pts on IFN treatment to evaluate benefit and tolerability.Methods: Medical record data were collected from 2004 until June 2018. Inclusion criteria: diagnosis of ET (WHO criteria) on treatment with IFN (IFN alpha-2a/b and PEG-IFN alpha-2a/b) with IFN follow-up time of at least 6 months.Results: 53 pts (36 female, median age 44 yrs, range 25-71 yrs), with a median age at diagnosis 37 yrs, range 14-63 yrs, were treated with IFN alpha-2a/b (11 pts) or PEG-IFN 2a/b (42pts). The median duration of IFN therapy was 4.2 yrs and median follow-up 9.0 yrs (range 1.4-27.3 yrs).Intermediate and high-risk ET, according to IPSET score, was identified in 27 pts (~50%), indications for treatment initiation in the low risk population (26 pts) included extreme thrombocytosis (17 pts), a thromboembolic event (TE) (1 pt), age over 60 yrs (1 pt), pregnancy (2 pts), high symptom burden (4 pts) and surgery (1 pt).Concerning driver mutation status, 22 (41.5%) pts had the JAK2 V617F mutation; 22 (41.5%) had CALR type 1/2 mutations, 8 (15%) were Triple negative and molecular information was lacking for 1 pt.Regarding treatment, the median time from diagnosis to first line of treatment was 0.6 yrs and IFN was initiated as first line therapy in 25 pts (~50%). The median number of lines of therapy prior to IFN was 2. The median time to obtain a haematological response (HR) on IFN (plts <400x 109/L) was ~10 months (range 0-45 months). At last follow-up, 40/53 pts were in HR and 13/53 pts in partial response (PR; arbitrarily defined as plts <700 X 109/L). 7 of the latter group remained on IFN treatment with a median plt count of 488 X 109/L (range 424-660 X 109/L) Overall 52.5% of the patients in HR were JAK2 V617F mutated and 71% of the patients who did not achieve HR were CALR positive.A total of 19 TE were reported in 15/53 pts (28%), 4 pts had 2 TE; abdominal thrombosis (2/19), cerebral thrombosis, including CVA, TIA and CVT (8/19), myocardial infarct (2/19), and other (retinal vein 2/19; upper and lower limbs 3/19 and digital ischemia (2/19). Of the cohort with TE, 47% were JAK2 V617F mutated, 20 % were CALR mutated and 33% were Triple Negative. Concerning IPSET score, 80 % were Intermediate (40%) and high-risk (40%) ET. Prior to or at diagnosis, 10 TE occurred and only 4 were diagnosed in patients on cytoreductive therapy. Of these 2/4 affected pts already on treatment had another thromboembolic risk factor: 1 pt with antiphospholipid syndrome had 2 episodes of digital ischemia; 1 pt had a second upper limb thrombosis (first at diagnosis in different localization) after a laparoscopic cholecystectomy, 2/4 did not achieve PR, 1 pt with poor compliance to IFN treatment had a lower limb thrombophlebitis and 1 pt had a TIA on HC; neither of these latter patients achieved a PR. None of the pts had a hemorrhagic complication on IFN.During a medium follow up period of 9 yrs, only 6 pts had to discontinue IFN therapy due to persistent, ≥ grade 3 toxicity: fatigue, depression or thyroiditis. No patient had disease progression.Discussion: In this young cohort of ET pts treatment with IFN was well tolerated with high rates of response and only 6/53 (11%) pts discontinuing. TE on IFN treatment were rare and all reported cases were in pts with an additional risk factor or in those who had not achieved a PR; this highlights important practice points for enhanced vigilance and consideration to therapy escalation or switch. Our data corroborates the previously reported efficacy of IFN in the treatment of ET, with an ability to control plts count and prevent thromboembolic and haemorrhagic events. Due to its efficacy and absence of leukaemogenic effect it should be considered as an option for first line treatment of young ET pts requiring cytoreductive therapy. DisclosuresMcLornan:Novartis: Speakers Bureau; Jazz Pharmaceutical: Speakers Bureau. Radia:Novartis: Speakers Bureau; Blueprint: Consultancy. Harrison:Gilead: Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau; CTI BioPharma: Consultancy, Honoraria.