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16 Anticoagulation Management of Splanchnic Vein Thrombosis in Myeloproliferative Neoplasms: A Global Abdominal/Splanchnic Thrombosis Retrospective Observational Study in 486 MPN Patients (GASTRO-MPN)

Program: Oral and Poster Abstracts
Type: Oral
Session: 332. Thrombosis and Anticoagulation: Clinical and Epidemiological: Thrombotic Risk: The Genes We're Born with and Mutations We Acquire
Hematology Disease Topics & Pathways:
Research, Bleeding and Clotting, MPN, Clinical Research, Thromboembolism, Chronic Myeloid Malignancies, Diseases, Real-world evidence, Registries, Myeloid Malignancies
Saturday, December 7, 2024: 10:15 AM

Chi-Joan How, MD1, Pavlina Chrysafi, MD2, Amica Ko3*, Rebecca Zon, MD4, Atefeh Ghorbanzadeh5*, Dahniel L Sastow, MD6, Maria Georgen7*, Abi Prabhu, MD7*, Vrushali Pachpande8*, Sai Sudha Valisekka8*, Mukul Agarwal, DM, MD, MBBS9*, Amiya Ranjan Nayak10*, May Anne Cheong11*, Alessandra Iurlo, MD, PhD12*, Daniele Cattaneo13*, Thita Chiasakul, MD14*, Rishi Dhawan15*, Kristen M. Sanfilippo, MD16, Gabriela S. Hobbs, MD17, Damon E. Houghton, MD, MS18, Joan D Beckman, MD, PhD19, Lisa Baumann Kreuziger, MD, MS20, Douglas Tremblay, MD21, Rushad Patell, MD22 and Mandy N. Lauw, MD, PhD23

1Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, MA
2Department of Medicine, Mount Auburn Hospital, Harvard Medical School, Cambridge, MA
3Erasmus University, Rotterdam, Netherlands
4Brigham and Women's Hospital, Boston
5Mayo Clinic, Rochester, MN
6Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY
7Medical College of Wisconsin, Milwaukee
8University of Minnesota, Minneapolis
9Dept of Hematology, All India Institute of Medical Sciences, New Delhi, Delhi, India
10All India Institute Of Medical Sciences, New Delhi, IND
11Singapore General Hospital, Singapore, Singapore
12Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
13FONDAZIONE IRCCS CA' GRANDA OSPEDALE MAGGIORE POLICLINICO, MILANO, ITA
14Center of Excellence in Translational Hematology, Division of Hematology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
15All India Institute Of Medical Sciences Delhi, New Delhi, India
16Washington University School of Medicine St Louis, Chesterfield, MO
17Division of Hematology/Oncology, Massachusetts General Hospital, Boston, MA
18Department of Cardiovascular Diseases, Division of Vascular Medicine & Dept of Medicine, Division of Hematology, Mayo Clinic, Rochester, MN
19University of Minnesota, Minneapolis, MN
20Versiti, Milwaukee, WI
21Division of Hematology & Oncology, Icahn School of Medicine at Mount Sinai, New York, NY
22Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA
23Department of Hematology, Erasmus University Medical Center, Rotterdam, Netherlands

Background: Myeloproliferative neoplasms (MPNs) are chronic leukemias with increased thrombotic risk. Venous thrombosis in MPN often occurs in atypical sites, such as splanchnic vein thrombosis (SVT), defined by thrombosis in the portal, hepatic, mesenteric, or splenic veins. Data to guide anticoagulation management of SVT in MPN patients is lacking.

Objectives: The purpose of this study is to evaluate outcomes as well as the safety and efficacy of different anticoagulation strategies in MPN patients with SVT.

Methods: A retrospective cohort study of MPN patients with SVT from 10 international centers was conducted. All centers performed systematic identification of adults with a World Health Organization 2016 diagnosis of an MPN (polycythemia vera [PV], essential thrombocythemia [ET], myelofibrosis [MF], prefibrotic MF, MPN-unclassifiable [MPN-U]) and confirmed SVT. Inclusion criteria were met if first SVT occurred after or within one year before MPN was diagnosed. The primary outcome was 1-year cumulative incidence of recurrent venous (VT) or arterial thrombosis (AT). Secondary outcomes included 1-year cumulative incidence of (1) major and clinically relevant non-major bleeding (CRNMB) by International Society on Thrombosis and Hemostasis criteria, (2) SVT recanalization; and (3) 1-year overall survival. Death as a competing risk was used for cumulative incidence analyses of recurrence and bleeding.

Results: 486 MPN patients (median age at first SVT 51 years; 62.3% female) were identified. MPN diagnosis preceded SVT in 35.2% of patients (median time 4.8 years) and occurred simultaneously or within 1 year of first SVT in 64.8% of patients. 43.8% of patients had PV, 23.7% ET, 14.2% MF, 3.1% prefibrotic MF and 13.2% MPN-U. The most common driver mutation was in JAK2 (90.7%) followed by CALR (4.4%) and MPL (1.6%). SVT localization was isolated to portal (25.7%), hepatic (15.4%), mesenteric (1.9%), and splenic veins (4.3%), and in 51.2% of cases SVT occurred in multiple vessels. Prior VT or AT occurred in 8.8% and 4.1% of subjects, respectively. Cytoreduction (most commonly hydroxyurea [36.9%], interferon [9.6%] or JAK inhibitor [6.8%]) was started after SVT in 58.7% of newly diagnosed MPN patients and 40.6% of those with known MPN.

57.6% of patients were anticoagulated, 3.5% of patients were treated with an antiplatelet agent, and 11.7% were treated with both. The most common initial anticoagulants were vitamin K antagonists (VKA) (29.2%), direct oral anticoagulants (DOAC; 20.4%), and low-molecular-weight heparin (LMWH; 10.5%). DOACs were more commonly used in the USA and Asia than Europe (21.2%, 52%, and 13.5%; p<0.001). The median duration of anticoagulation was 23.9 months, with 62.8% still on anticoagulation after 3 years or at last follow-up.

1-year cumulative incidence of recurrent VT and AT was 14% (95% CI 11-18) (5.8% for recurrent SVT [95% CI 3.9-8.3]; 6.3% for other VT [95% CI 4.3-8.8]; 2.4% for AT [95% CI 1.3-4.2]), with an overall time to event 89 (IQR 34-193) days. Thrombosis incidence was similar in patients initially treated with VKA (13%), DOAC (15%) or LMWH (16%) (p=0.93); in comparison, individuals not treated with anticoagulation had 1-year thrombosis incidence of 13% (p=0.22). 1-year major and CRNMB cumulative incidence in all patients was 5.8% (95% CI 3.9-8.2) and 8.5% (95% CI 6.1-11), with median time to event 68 (IQR 13-150) days. Incidence of major bleeding was similar in VKA, DOAC, and LMWH-treated patients (5.9%, 6.6%, and 4.0%; p=0.89). 1-year cumulative incidence of SVT (partial) recanalization was 13% (95% CI 9.8-16) in all patients, with a median time to recanalization of 127 (IQR 40-323) days; recanalization rates were similar in anticoagulated and non-anticoagulated patients (p=0.76). There was a trend toward higher recanalization rates in patients treated with DOAC (26.9%) than with VKA (21.5%) or LMWH (13.6%; p=0.28). 1-year overall survival was 94.2% (95% CI 91.8-96.1) and similar between treatment groups (VKA 96.7%, DOAC 95.6%, LMWH 89.7%; p=0.11) and for no anticoagulation (82.3%; p=0.32).

Conclusions: This is the largest contemporary cohort of MPN patients with SVT. MPN patients with SVT remain at risk for short-term thrombosis and bleeding complications regardless of treatment. We found no significant differences in outcomes between anticoagulation strategies, including in patients treated with DOACs compared to VKA or LMWH.

Disclosures: How: PharmaEssentia: Consultancy; Merck: Consultancy. Zon: Triveni Bio: Consultancy, Current equity holder in private company. Iurlo: AOP: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Hobbs: GSK: Honoraria; Incyte: Honoraria, Research Funding; BMS: Honoraria; Pfizer: Honoraria; Pharmaessentia: Honoraria; Novartis: Honoraria; Sobi: Honoraria; Cogent: Honoraria; Abbvie: Honoraria; Regeneron: Other: spouse employment. Houghton: Bayer: Research Funding; Veralox: Research Funding. Beckman: Novartis: Research Funding; Bayer: Research Funding. Baumann Kreuziger: Takeda: Research Funding; CSL Behring: Research Funding; Sanofi: Research Funding; Veralox: Research Funding. Tremblay: Sobi: Consultancy, Research Funding; Sumitomo: Research Funding; Cogent Biosciences: Consultancy, Research Funding; Gilead: Research Funding; Novartis: Consultancy; Abbvie: Consultancy; Pharmaessentia: Consultancy; Sierra Oncology: Consultancy; GSK: Consultancy. Patell: Merck Research: Consultancy, Other: Personal fees. Lauw: BMS/Pfizer: Consultancy; Viatris: Consultancy; Bayer: Consultancy; Inari: Consultancy; ZonMw: Research Funding; GlaxoSmithKline: Research Funding; Leopharma: Research Funding.

*signifies non-member of ASH