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Introduction Response criteria for judging the success of PV therapeutic interventions put forth by the ELN (Barosi Blood 2013 ) require normalization of blood counts and splenomegaly for 3 months following the administration of an agent. These criteria are frequently employed as a primary outcome in clinical trials, yet, the clinical significance of meeting these criteria have not been established. The goal of this study is to evaluate the prognostic impact of ELN response criteria in a large US retrospective database of PV patients (Ronner Blood 2020). Methods Included patients were age ≥18 years at diagnosis, met 2016 WHO diagnostic criteria for PV, and were treated with a cytoreductive agent including hydroxyurea (HU), pegylated-interferon or ruxolitinib for at least 12 weeks. Laboratory and spleen measurements were collected throughout the treatment course. Attaining an ELN response throughout the study period was defined as concurrent WBC Multivariable Cox proportional hazards methods were used to determine the associations between achieving an ELN response and events such as thrombosis, disease progression (development of myelofibrosis [MF], myelodysplastic syndrome [MDS], or myeloproliferative neoplasm in blast phase [MPN-BP] as clinically determined by treating physician) and death. Time-dependent Cox proportional hazards models were also assessed to examine the relationship between duration of response and these outcomes. All models were adjusted for age, gender, history of prior thrombosis, and the presence of cardiovascular (CV) risk factors. Results A total of 398 of the 527 patients received cytoreductive therapy for at least 12 weeks and were included in the current analysis. Baseline characteristics are shown in the Table. HU was the most common initial cytoreductive agent employed. The median maximum dose of HU was 1000mg daily (IQR 714-1500). During a median follow-up of 52.3 months, 249 (63%) patients attained an ELN response and 149 (37%) did not. The median duration of response was 37 weeks (IQR 16-74). Forty-five patients (11%) experienced a new thrombosis, including DVT (n=15), CVA/TIA (n=14), PE (n=5), MI (n=6), and splanchnic vein thrombosis (n=6). Disease progression occurred in 51 (13%) patients, including MF (n=47), MDS (n=3), and MPN-BP (n=1). Thirteen patients (3%) died during follow up. In our Cox-proportional hazards model, meeting an ELN response was not associated with a reduced risk of developing a thrombosis (p=0.86), but having a prior thrombosis was associated with acquiring a subsequent thrombosis (HR 3.3, 95% CI 1.80-6.05). Similarly, ELN responses were not associated with reduction in hazard of death (p=0.80). However, an ELN response was associated with a significant decrease in the hazard of progression (HR 0.47, 95% CI 0.27-0.83) (Figure). Advanced age at diagnosis was also associated with an increased hazard of progression (HR 1.03, 95% CI 1.01-1.05). Similar results were observed when examining the relationship of ELN response duration as a time-dependent covariate as it relates to thrombosis (HR 0.82, 95% CI 0.41-1.65), progression (HR 0.39, 95% CI 0.17-0.90) and death (HR 0.82, 95% CI 0.23-2.88). We also evaluated the contribution of individual ELN response components using a multivariable Cox model adjusted for age, sex, prior thrombosis, and CV risk factors. The decrease in hazard of progression was largely driven by two components: WBC Conclusions Achieving an ELN response in PV patients is not associated with a reduction of risk for thrombosis or death but may be a surrogate endpoint for delaying disease progression. When evaluating new therapeutic strategies with the primary goal of reducing thrombotic burden in PV, the present ELN response criteria are not informative. The development of new reliable surrogate endpoints for predicting thrombotic risk are required in order to rapidly evaluate interventions that can prevent thrombosis in PV patients. Figure 1 Figure 1. Disclosures Podoltsev: Incyte: Honoraria; Novartis: Honoraria; Blueprint Medicines: Honoraria; Pfizer: Honoraria; PharmaEssentia: Honoraria; CTI BioPharma: Honoraria; Bristol-Myers Squib: Honoraria; Celgene: Honoraria. Gotlib: Allakos: Consultancy; Cogent Biosciences: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Chair for the Eligibility and Central Response Review Committee, Research Funding; PharmaEssentia: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kartos: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Deciphera: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Blueprint Medicines: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Heaney: Cogent: Research Funding; CTI: Honoraria, Research Funding; BMS: Research Funding; Blueprint: Honoraria, Research Funding; Sierra Oncology: Research Funding; Kartos: Research Funding; Novartis: Honoraria. Kuykendall: Abbvie: Honoraria; Blueprint: Honoraria; Novartis: Honoraria, Speakers Bureau; Incyte: Consultancy; Protagonist: Consultancy, Research Funding; Pharmaessentia: Honoraria; Celgene/BMS: Honoraria. Shammo: Incyte: Consultancy, Honoraria, Research Funding, Speakers Bureau; CTI pharma: Research Funding; Stemline therapeutics: Research Funding; Kartos Pharma: Research Funding; Takeda: Consultancy, Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company, Honoraria, Research Funding; Abbvie: Current holder of individual stocks in a privately-held company, Research Funding; Baxter: Current holder of stock options in a privately-held company; sanofi: Consultancy, Honoraria, Speakers Bureau; NS Pharma: Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Alexion: Consultancy, Honoraria, Research Funding, Speakers Bureau; Apellis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Astra zeneca: Research Funding. Mesa: La Jolla Pharma: Consultancy; Incyte Corporation: Consultancy, Research Funding; CTI: Research Funding; Samus: Research Funding; Pharma: Consultancy; Sierra Oncology: Consultancy, Research Funding; Novartis: Consultancy; AOP: Consultancy; Promedior: Research Funding; Constellation Pharmaceuticals: Consultancy, Research Funding; Abbvie: Research Funding; CTI: Research Funding; Gilead: Research Funding; Celgene: Research Funding; Genentech: Research Funding. Yacoub: Incyte: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees; ACCELERON PHARMA: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Dynavex: Current equity holder in publicly-traded company; Cara: Current equity holder in publicly-traded company; Ardelyx: Current equity holder in publicly-traded company; Seattle Genetics: Honoraria, Speakers Bureau; Hylapharm: Current equity holder in publicly-traded company. Hoffman: Protagonist Therapeutics, Inc.: Consultancy; Kartos Therapeutics, Inc.: Research Funding; Novartis: Other: Data Safety Monitoring Board, Research Funding; AbbVie Inc.: Other: Data Safety Monitoring Board, Research Funding. Mascarenhas: AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kartos: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Constellation: Consultancy, Membership on an entity's Board of Directors or advisory committees; Geron: Consultancy, Research Funding; Merus: Research Funding; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; PharmaEssentia: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sierra Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Geron: Consultancy; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Prelude: Consultancy; Promedior: Consultancy, Membership on an entity's Board of Directors or advisory committees; Galecto: Consultancy; CTI Biopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Forbius: Research Funding.

Introduction: Hypomethylating agents (HMAs) are used as induction therapy for patients with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy. HMA therapy is frequently initiated in the hospital and some patients remain hospitalized through the initiation of cycle 2 (C2). Clinicians are often faced with the decision to administer C2 while the patient is still hospitalized, however, there is a paucity of prognostic information to guide treatment decisions in this common scenario. Methods: We conducted a retrospective review of patients diagnosed with treatment naïve, de novo and secondary AML who were ineligible for induction chemotherapy (at the discretion of the treating physician based on advanced age, comorbidities, or other reasons) at a single, tertiary, referral center. Patients were included if they received induction therapy with an HMA, including azacitidine and decitabine between 7/1/2008 and 7/1/2018. Exclusion criteria included receipt of intensive induction chemotherapy and inadequate electronic medical documentation. Patients were divided into four groups: patients who were discharged after completion of C1 and received C2 as an outpatient (discharged after C1), patients who received C1 and C2 during the same hospitalization (C1-C2 continuous hospitalization), those who received one total cycle (C1 only), and patients who received C1 as an outpatient (C1 outpatient). The groups were analyzed separately for the primary outcome of overall survival (OS), calculated by Kaplan Meier analysis. Results: Out of 105 patients identified who received an HMA, 100 patients were identified who met inclusion/exclusion criteria and their baseline characteristics are shown in Table 1. Most patients had de novo AML (39.0%), although 33.0% and 19.0% of patients had AML secondary to myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN), respectively. Additionally, 8 patients (8.0%) had therapy related AML. The majority of patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 1 or 2 at induction. Patients who received C1 as an outpatient had a significantly better performance status than those who did not (p= 0.033) Decitabine was the most common HMA (57.0%) administered and was most often on 5-day schedule. Eight patients (8.0%) were continually hospitalized until C2, 5 because of active medical issues (most often fevers requiring intravenous antibiotics), 2 had physical debility precluding discharge home, and 1 was receiving intrathecal chemotherapy twice weekly for central nervous system involvement of AML. The median OS was 15.6 months (95% CI 2.66-28.6) in patients who received C1 outpatient, 10 months (95% CI 6.67-13.43) in patients discharged after C1, 4 months (95% CI 2.40-6.40) in the C1-C2 continuous hospitalization group, and 1 month (95% CI 0.61-1.30) in those who only received C1 as shown in Figure 1. Patients discharged after C1 had a significantly longer OS compared to the C1-C2 continuous hospitalization group (p=0.003). There was a trend (p=0.054) towards worse survival in patients who received C1 only compared to patients hospitalized continually from C1-C2. Conclusions: Continued hospitalization from C1 to C2 of HMA therapy led to an extremely poor median survival of 4 months in this cohort, compared to 10 months in patients who were able to be discharged after C1 and receive C2 as an outpatient. Patients who only received a single cycle of HMA did not have a significantly different survival as compared to patients who were continually hospitalized from C1 to C2. While this is a small retrospective series, these data suggest that AML patients still requiring hospitalization at time of C2 of HMA therapy should be re-evaluated for alternative therapeutic approaches including hospice given poorer outcomes. Although this grouping selects for patients who are sicker and unable to leave the hospital, there is apparent lack of significant benefit of continued HMA therapy in the majority of patients while inpatient. The impact on hospital length of stay, unnecessary utilization of healthcare resources, and patient's quality of life should also be considered in these cases. Prospective identification of these patients with a poorer prognosis could lead to better alternatives for therapeutic approaches. Disclosures Kremyanskaya: Incyte, Celgene, Constellation, Protagonist.: Research Funding; La Jolla: Consultancy. Navada:Onconova Therapeutics Inc: Research Funding. Mascarenhas:Merus: Research Funding; Pharmaessentia: Consultancy, Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Promedior: Research Funding; Roche: Consultancy, Research Funding; Janssen: Research Funding; CTI Biopharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Introduction: Anticoagulation (AC) is the standard therapy for non-cirrhotic portal vein thrombosis (PVT). Professional society guidelines and expert opinions currently favor the use of vitamin K antagonists (VKAs) or low molecular weight heparins (LMWHs) for the treatment of PVT. Routine use of direct oral anticoagulants (DOACs) in PVT has often been met with concern due to a lack of data. We investigated the efficacy and safety of DOACs for the treatment of non-cirrhotic PVT, and compared them to standard therapies (VKAs and LMWHs). Methods: We conducted a retrospective review of patients treated at a tertiary care center. Patients were identified who had a documented PVT with or without concurrent thrombosis in additional splanchnic vessels, followed between 1/1/2000 and 2/1/2019. Patients were excluded if they had cirrhosis or tumor thrombus, received thrombectomy, lacked baseline imaging of PVT at diagnosis, or lacked subsequent follow-up imaging at least 3 months following diagnosis. The initial long-term AC used in each instance was recorded and formed the basis for comparison. In many cases intravenous heparin was used as initial short-term AC, and in these instances the first long-term AC transitioned to thereafter was regarded. The primary outcome was complete radiographic resolution of PVT (established on follow-up imaging). Secondary outcomes included recanalization (with or without complete resolution) of occlusive PVT, development of chronic portal hypertensive symptoms (cPHS, defined as new or worsening esophageal varices demonstrated on EGD, or new or worsening ascites requiring diuretic medications), and major (WHO grade 3 or 4) bleeding. Hazard ratios for each outcome were calculated via multivariable (MV) analysis. Results: A total of 330 patients were included. Their characteristics and treatments are described in Table 1. There were a variety of predisposing factors for PVT. Of note 27% (n=90) had no evident predisposing factor. A wide variety of ACs were used. Although the most commonly used ACs were the standard therapies warfarin (n=108) and enoxaparin (n=70), many patients received DOACs (n=93), most often rivaroxaban (n=65). Figure 1 shows the primary outcome of complete radiographic resolution (CR) stratified by AC. The CR rate was significantly higher among patients who received AC (49%) than those who did not (14%) (p There were similar findings when comparing rates of recanalization of occlusive PVT (no AC 2/29= 7%, any AC 71/159=45%, dabigatran 4/5=80%, rivaroxaban 22/35=63%, apixaban 7/13 =54%, enoxaparin 16/36=44%, warfarin 21/68=31%). On MV analysis warfarin was inferior to each DOAC with respect to recanalization of occlusive PVT. Development of cPHS occurred in 30/57 (52%) of patients who received no AC compared with 52/273 (19%) of those who received AC (p=.0093). Although there was a trend toward less cPHS among those receiving rivaroxaban compared with warfarin (rivaroxaban 5/65=8%, enoxaparin 13/70=19%, warfarin 31/108=29%), this difference was not statistically significant on MV analysis. Major bleeding rates were not significantly different with or without AC, or among the various ACs. Among predisposing factors for PVT, patients harboring JAK2V617F had notably poor outcomes compared to those with other known predisposing factor (CR 8% vs 55% p=.0016; recanalization 16% vs 49% p=.0036; development of cPHS 49% vs 17% p=.5492). The 90 patients with no evident predisposing factor also demonstrated worse outcomes compared to those with evident non-JAK2 predisposing factors (CR 31% vs 55% p= .0152; recanalization 33% vs 49% p=.0896; development of cPHS 32% vs 17% p=.7406). Conclusions: DOACs are safe and effective for treatment of non-cirrhotic PVT. Use of warfarin is associated with inferior outcomes among non-cirrhotic PVT patients when compared with other forms of AC. Patients harboring JAK2V617, and to a lesser extent those without a clear predisposing factor for PVT, have inferior outcomes compared with other non-cirrhotic PVT patients. Disclosures Mascarenhas: Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Roche: Consultancy, Research Funding; Merck: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; CTI Biopharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Research Funding; Promedior: Research Funding; Merus: Research Funding; Pharmaessentia: Consultancy, Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: This abstract will discuss the use of direct oral anticoagulants including rivaroxaban, apixaban, and dabigatran, for anticoagulation of portal and other splanchnic vein thrombosis.