-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

242 Revised ELN Criteria in Polycythemia Vera Identify an Increased Risk Phenotype for Thrombotic Events Beyond Conventional Risk Stratification. a Multicenter Cooperative Study

Program: Oral and Poster Abstracts
Type: Oral
Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Personalized and Molecular Approaches in Myeloproliferative Neoplasms: Risk Stratification and Therapeutic Implications
Hematology Disease Topics & Pathways:
Research, Clinical Research, Real-world evidence
Saturday, December 7, 2024: 2:15 PM

Francesca Palandri, MD, PhD1*, Elena Maria Elli, MD2*, Giulia Benevolo, MD3*, Alessandra Dedola4,5*, Roberto Latagliata6*, Erika Morsia7*, Mario Tiribelli, MD8*, Francesco Cavazzini, MD9*, Alessia Tieghi, MD10*, Mirko Farina, MD11*, Alessandra D'Addio, MD12*, Elisabetta Abruzzese, MD13, Fabrizio Cavalca14*, Rikard Mullai, MD15*, Antonio Cuneo, MD16*, Bruno Martino, MD17*, Florian Heidel, MD18, Elena Rossi, MD19*, Massimo Breccia20*, Valerio De Stefano, MD19* and Filippo Branzanti, MSc5,21*

1IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico S. Orsola-Malpighi, Istituto di Ematologia "Seràgnoli", Bologna, Italy
2Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
3Hematology Division I, Department of Molecular Biotechnologies and Health Sciences, University of Turin/University Hospital A.O.U. “Città della Salute e della Scienza”, Turin, Italy
4IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli”, Bologna, Bologna, Italy
5Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Bologna, Italy
6Hematology Unit, Ospedale Belcolle, Viterbo, Italy, Rome, ITA
7Hematology Unit, Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Ancona, Italy
8Division of Hematology and BMT, Department of Medical Area, University of Udine, Udine, Italy
9Division of Hematology, Arcispedale Sant'Anna, University of Ferrara, Ferrara, ITA
10Department of Hematology, Azienda USL - IRCCS di Reggio Emilia, Reggio Emilia, Italy
11Unit of Blood Diseases and Bone Marrow Transplantation, Cell Therapies and Hematology Research Program, Department of Clinical and Experimental Science, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy
12Division of Hematology, Onco-hematologic Department, AUSL della Romagna, Ravenna, Ravenna, ITA
13Division of Hematology, Ospedale S. Eugenio, Roma, Roma, Italy
14IRCCS San Gerardo dei Tintori, divisione di ematologia e unità trapianto di midollo, Monza, Monza, Italy
15Division of Hematology and BMT, Department of Medical Area, University of Udine, Udine, Udine, Italy
16Division of Hematology, University of Ferrara, Ferrara, Ferrara, Italy
17Division of Hematology, Azienda Ospedaliera 'Bianchi Melacrino Morelli', Reggio Calabria, Italy
18Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Hannover Medical School (MHH), Hannover, Hannover, Germany
19Fondazione Policlinico Gemelli IRCCS, Section of Hematology, Catholic University, Rome, Roma, Italy
20Department of Translational and Precision Medicine, Az., Hematology-Sapienza University, Rome, Italy
21IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli”, Bologna, Italy

Introduction

The European LeukemiaNet (ELN) criteria for initiating cytoreductive therapy aim to manage this risk, primarily using hydroxyurea (HU) (Marchetti M et al, Lancet Haematol 2022). However, the impact of ELN criteria for therapy start (CTS) on thrombotic risk, particularly among low-risk (LR, age <60 yrs & no previous thromboses) and high-risk (HR: HR-AGE, age >60 yrs; HR-THRO: previous thrombosis regardless of age) patients (pts), needs further exploration.

Aims

This study evaluates the incidence of thrombosis among PV pts undergoing HU treatment across different risk categories and the impact of CTS on thrombotic risk.

Methods

The PV-ARC study (NCT06134102) is a multicenter, retrospective study of 1162 WHO2022 PV pts.

Among these, 739 pts treated with HU were evaluated for CTS, which were revised to apply real-world practice as follows: 1) persistent/progressive leucocytosis: 100% increase if white blood cells (WBC) <10 x109/L or 50% increase if WBC>10 or WBC>15 at diagnosis and HU start; 2) extreme persistent thrombocytosis: platelet (PLT) >1000 x10 9/L at diagnosis and HU start; 3) progressive splenomegaly: >5 cm below costal margin (BCM) from diagnosis; 4) inadequate hematocrit (HCT) control: 5) >6 phlebotomies (PHL)/yr or HCT >53% at diagnosis and HU start or PHL intolerance; 6) uncontrolled cardiovascular risk factors; 7) severe itching (score ≥5/10).

Incidence rate ratios (IRR) were calculated per 100 patient-years (%p-y). Thrombosis-free survival (TFS) was assessed using Kaplan-Meier analysis from HU start, and multivariate Cox regression analysis was used to identify factors independently associated with thrombotic risk.

Results

Among the 739 HU-treated pts, 137 (18.5%) were LR and 602 (81.5%) HR (HR-AGE: 70.4%; HR-THRO: 29.6%). Revised CTS were identified in 445 (60.3%) pts: 95 (69.3%) LR, 242 (57.1%) HR-AGE, and 109 (61.2%) HR-THRO, with a significant difference between LR and HR pts. More than one CTS was present in 152 (34.1%) pts, mainly in LR pts (43.2% LR vs. 31.6% HR, p=0.02).

Additional reasons to start HU (spleen palpable at 2-5 cm BCM, mild leucocytosis/thrombocytosis, microvascular disturbances, PHL requirement <6/yr) were present in 100% LR and in 71.3% HR pts without CTS.

Median HU starting dose was 0.5 g/die (34.2% received ≥1 g/d). Over time, maximum HU dose was ≥1 g/d more frequently in LR (70.3%), compared to HR-THRO pts (48.7%, p=0.05) and HR-AGE (41.9%, p=0.005) pts.

Antiplatelets and/or anticoagulants were used in 94.5% of pts, comparably across risk categories.

The IRR of thrombosis during HU was 1.7 %p-y. It was similar in LR and HR-AGE pts (1.1 vs 1.3 %p-y, p=0.68) but significantly higher (3.0 %p-y) in HR-THRO pts (p=0.006 vs LR and p=0.002 vs HR-AGE). The IRR of arterial thrombosis was significantly higher in HR-THRO pts (1.1 %p-y) compared to LR (0.4 %p-y, p=0.05) and comparable to HR-AGE (0.6 %p-y, p=0.10). The IRR of venous thrombosis was significantly higher in HR-THRO pts (1.3 %p-y) compared to both LR (0.5 %p-y, p=0.05) and HR-AGE (0.6 %p-y, p=0.02).

CTS were associated with a significantly increased IRR of thrombosis in the total cohort (2.2 vs 0.7 %p-y, p<0.001) and across all risk categories: LR pts (1.6 vs 0 %p-y, p=0.05), HR-AGE pts (2.0 vs 0.5 %p-y, p=0.001), and HR-THRO pts (4.0 vs 1.7 %p-y, p=0.04).

During HU treatment, TFS at 5 years was 88.7% in pts with CTS compared to 96.1% in those without CTS (p<0.001). Across all the risk categories, best TFS at 5 yrs was observed in LR and HR-AGE (LR with no CTS, 100%; HR-AGE with no CTS: 97.8%). LR/HR-AGE pts with CTS and HR-THRO pts with no CTS had comparable TFS (86.4%, 91.4% and 88.1%, respectively). HR-THRO pts with CTS had the worse TFS (79.5%).

Multivariate Cox analysis considering CTS, age>60 yrs and previous thrombosis, confirmed that CTS (HR: 3.1, p<0.001) and previous thrombosis (HR: 3.2, p<0.001) were independent predictors of thrombotic risk.

Conclusion

This study demonstrates that ELN criteria for therapy start effectively identify PV pts at increased thrombotic risk, regardless of their conventional risk category. These findings highlight the need for incorporating CTS into existing prognostic models to improve risk stratification and therapeutic decision-making in PV. Additionally, the data suggest that most LR pts require HU due to CTS, emphasizing the necessity for tailored management strategies and further research into the long-term impact of HU therapy in younger pts.

Disclosures: Palandri: BMS/Celgene: Consultancy, Honoraria; Sierra Oncology: Consultancy, Honoraria; CTI: Consultancy, Honoraria; Sobi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Constellation-Morphosys: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Telios: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AOP: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Elli: BMS: Membership on an entity's Board of Directors or advisory committees; ABBVIE: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Benevolo: Novartis: Honoraria; BMS: Honoraria; Janssen: Honoraria; GSK: Honoraria. Latagliata: BMS: Honoraria; Abbvie: Honoraria; Novartis: Consultancy, Honoraria. Abruzzese: Novartis: Consultancy; Ascentage: Consultancy; MorphoSys: Consultancy; Pfizer: Consultancy; Incyte: Consultancy; BMS: Consultancy. Cuneo: AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: support for attending meetings; BeiGene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: support for attending meetings; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: support for attending meetings; Lilly: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: support for attending meetings; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: support for attending meetings. Martino: Janssen: Speakers Bureau; Novartis: Speakers Bureau; AstraZeneca: Speakers Bureau; Incyte: Speakers Bureau. Heidel: Hannover Medical School: Current Employment; CTI: Consultancy, Honoraria; Celgene: Consultancy, Research Funding; Novartis: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria; AOP: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Merck: Consultancy, Honoraria. Breccia: Abbvie: Honoraria; BMS: Honoraria; AOP: Honoraria; Incyte: Honoraria; Novartis: Honoraria; Pfizer: Honoraria; GSK: Honoraria. De Stefano: Novartis: Membership on an entity's Board of Directors or advisory committees; Sobi: Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees; Abbvie: Speakers Bureau; Alexion: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; BMS: Speakers Bureau; Grifols: Speakers Bureau; Leo Pharma: Speakers Bureau; Novartis: Speakers Bureau; Novo Nordisk: Speakers Bureau; Sanofi: Speakers Bureau; Takeda: Speakers Bureau; Alexion: Research Funding; Grifols: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Argenx: Membership on an entity's Board of Directors or advisory committees; AOP: Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH