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241 Prognostic Value of Response to First-Line Hydroxyurea According to Ipset Stratification in Essential Thrombocythemia

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:
Clinical Practice (Health Services and Quality), MPN, Chronic Myeloid Malignancies, Diseases, Treatment Considerations, Non-Biological therapies, Myeloid Malignancies
Saturday, December 7, 2024: 2:00 PM

Marta Santaliestra1*, Marta Garrote2*, María Soledad Noya3*, Manuel Pérez-Encinas4*, María Alicia Senin5*, Raul Perez Lopez6*, Francisca Ferrer Marin, MD7,8, Gonzalo Carreño, PhD9*, Gonzalo Caballero Navarro10*, Elena Magro11*, Patricia Velez, MD12*, Miguel A. Cortes Vázquez13*, Ana Moreto Quintana14*, Anna Angona15*, Irene Pastor Galan16*, Jose María Guerra17*, M. Carmen Garcia Hernandez18*, María Isabel Mata19*, Ruth Stuckey, PhD20*, Maria Teresa Gómez Casares21*, Maria Laura Fox, MD22*, Beatriz Cuevas23*, Valentín García Gutiérrez Sr.24, Ana Triguero25*, Eduardo Arellano-Rodrigo26*, Juan Carlos Hernandez Boluda, MD, PhD27* and Alberto Alvarez-Larran28*

1Hospital Universitari Mútua Terrassa, Barcelona, Spain
2Hematopathology Section, Pathology Department, Hospital Clínic Barcelona, Barcelona, Spain
3Complexo Hospitalario Universitario de A Coruña, A Coruña, Spain
4Hospital Clínico Universitario, Santiago de Compostela, Spain., Santiago, Spain
5Hospital del Mar, Barcelona, Spain
6Hospital Universitario Virgen de la Arrixaca, Murcia, Spain
7UCAM, Murcia, Spain
8Hospital Universitario Morales Meseguer. Centro Regional de Hemodonación. Universidad de Murcia. IMIB-Arrixaca, Murcia, Spain
9Hospital Universitario 12 de Octubre, Madrid, Spain
10Hematology Department. Hospital Miguel Servet, Zaragoza, Spain., Zaragoza, ESP
11Hematology Department. Hospital Príncipe de Asturias, Alcalá de Henares, Spain., Alcalá de Henares, Spain
12Department of Hematology, Hospital del Mar, Barcelona, Spain
13Hematology Department. Hospital Marqués de Valdecilla, Santander, Spain, Santander, Spain
14Hospital Universitario de Cruces, Barakaldo, Spain
15Hospital Universitario Doctor Josep Trueta - ICO, Girona, Spain
16Department of Hematology, Hospital Clínico Universitario-INCLIVA, Valencia, ESP
17Hospital Son Llatzer, Palma de Mallorca, Spain
18Hematology Department, Hospital General Universitario de Alicante, Alicante, ESP
19Hematology Department. Hospital Costa del Sol, Marbella, Spain, Marbella, Spain
20Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas, Spain
21Hospital Universitario Doctor Negrín, Las Palmas, Spain
22Hematology Department, Vall d'Hebron University Hospital, University Autònoma of Barcelona (UAB), Barcelona, Spain
23Hospital de Burgos, BURGOS, ESP
24Hematology, Hospital Universitario Ramón y Cajal, Madrid, Spain
25Hospital Clínic de Barcelona, Barcelona, Spain
26Department of Hemotherapy and Hemostasis, Hospital Clinic, Barcelona, Spain
27Hospital Clínico Universitario-INCLIVA, VALENCIA, Spain
28Hematoloy Department,, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain

INTRODUCTION

Essential thrombocythemia (ET) is the most frequent chronic myeloproliferative neoplasm and the one with the best prognosis. ET patients are classically stratified into two thrombotic risk categories based on age over 60 years and history of thrombosis. Recently, the increased thrombotic risk associated with JAK2 mutation has been incorporated into the revised IPSET-thrombosis scoring system. Hydroxyurea (HU) is the first-line treatment for the majority of patients with ET, but criteria for treatment change are not well-established. The prognostic value of the response according to the revised-IPSET thrombosis risk score has not been studied.

OBJECTIVES

Our aim was to analyze the prognostic impact of achieving complete hematological response (CHR) and resistance/intolerance (R/I) to HU, as defined by the European LeukemiaNet, in a contemporary cohort of 1080 patients from the Spanish registry of ET. Subgroup analyses were also conducted based on both classical and revised IPSET-thrombosis risk stratification.

METHODS

The main outcomes of the study were survival, the occurrence of thrombotic events, bleeding, and disease progression. The period at risk was defined as the time elapsed from HU start to the first event.

RESULTS

Patients were classified at the time of cytoreduction according to the classical risk scale (low- n=144, high-risk n=936) and revised IPSET-Thrombosis stratification (very low- n= 61, low- n=83, intermediate- n= 261, and high-risk n=675). With a median treatment duration of 5 years (IQR: 2.4-8.2), 720 (67%) patients achieved CHR and 219 (20%) developed R/I to HU. The median time to CHR was 352 days, with probabilities of CHR at 12 and 24 months being 51% and 61%, respectively. The probabilities of R/I to HU at 1, 3, and 5 years were 4%, 9%, and 13%, respectively. Patients achieving CHR had significantly longer survival compared to non-responders, both in the intermediate-risk category (median survival: 17 and 11 years, respectively, p<0.001) and high-risk category (15.5 and 12.5 years, respectively, p=0.02). No differences in survival were observed according to R/I. High-risk patients achieving CHR also had a lower risk of arterial thrombosis (HR: 0.35, 95% CI: 0.2-0.6, p=0.001). There was not significant association between the development of R/I to HU and the probability of thrombosis. CHR and R/I rates were not associated with an increased risk of bleeding. CHR was associated with a lower probability of progression to myelofibrosis (MF). The absence of CHR was associated with a higher probability of MF in intermediate-risk (10-year probability: 5% vs 23% in responders and non-responders, respectively, p=0.01) and high-risk patients (10-year probability: 6% vs 15% in responders and non-responders, respectively, p=0.03), according to revised IPSET-Thrombosis. Subgroup analysis showed a higher probability of acute myeloid leukemia (AML) only in non-responders intermediate-risk patients. Fulfilling any of the criteria of R/I was associated with a higher probability of MF, but not of AML. When analyzed separately, only cytopenia has a higher risk of disease progression (10-year probability of MF: 5,7% vs 17,4% in responders and no-responders, respectively, p<0.001; 10-year probability of AML: 3% vs 11% in responders and no-responders, respectively, p=0.01).

CONCLUSION

In conclusion, CHR with first-line HU is a relevant prognostic factor that correlates with significant better survival and a lower rate of disease progression in patients categorized as high- and intermediate-risk according to revised IPSET-thrombosis stratification. Moreover, high risk patients achieving CHR face a lower risk of arterial thrombosis. The results of the present study support that failure to achieve CHR could be regarded as a valuable criterion for selecting candidates for second-line therapy.

Disclosures: Santaliestra: Novartis: Consultancy; GSK: Speakers Bureau. Perez Lopez: Pfizer: Honoraria. Ferrer Marin: Incyte, CTI BioPharma: Research Funding; Novartin, Celgene: Consultancy. Velez: Novartis: Speakers Bureau; GSK: Speakers Bureau. Fox: Novartis: Honoraria, Other: Travels and grants. García Gutiérrez: Novartis, Incyte: Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; CTA: Honoraria; GSK: Consultancy; Novartis, Incyte, GSK, Pfizer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis BMS Pfizer Incyte GSK: Consultancy. Alvarez-Larran: AOP: Consultancy.

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