Outcomes and effect of somatic mutations after erythropoiesis stimulating agents in patients with lower-risk myelodysplastic syndromes-Reference-Cited by-同舟云学术

Outcomes and effect of somatic mutations after erythropoiesis stimulating agents in patients with lower-risk myelodysplastic syndromes

Published:2024-01 Issue: Volume:15 Page:
ISSN:2040-6207
Container-title:Therapeutic Advances in Hematology
language:en
Short-container-title:Therapeutic Advances in Hematology

Author:

Caballero Juan Carlos¹^ORCID,Dávila Julio²,López-Pavía María³⁴⁵,Such Esperanza³⁴⁵,Bernal Teresa⁶,Ramos Fernando⁷,Calabuig Marisa⁸,Hernández Sánchez Jesús María⁹,Pomares Helena¹⁰,Sánchez Barba Mercedes¹¹,Abáigar María⁹,González Bernardo¹²,Merchán Brayan¹³,Sancho-Tello Reyes¹⁴,Callejas Marta¹⁵,Muñoz-Novas Carolina¹⁶,Cerveró Carlos¹⁷,Sanz Guillermo³⁴⁵,Hernández Rivas Jesús María¹⁸¹⁹²⁰,Díez Campelo; María²¹²⁰

Affiliation:

1. Hematology Department, Hospital Clínico Universitario de Valladolid, Valladolid, Spain

2. Hematology Department, Hospital Nuestra Señora de Sonsoles, Ávila, Spain

3. Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain

4. CIBERONC, Instituto de Salud Carlos III, Madrid, Spain

5. Universidad de Valencia, Valencia, Spain

6. Hematology Department, Hospital Universitario Central de Asturias, Oviedo, Spain

7. Hematology Department, Hospital Universitario de León, León, Spain

8. Hematology Department, Hospital Clínico Universitario de Valencia, Valencia, Spain

9. Instituto de Biología Molecular y Celular del Cáncer, Instituto Biosanitario de Salamanca, Centro de Investigación del Cáncer, USAL-CSIC, Salamanca, Spain

10. Hematology Department, Hospital Universitario de Bellvitge-Hospital Duran I Reynals, Instituto Catalán de Oncología, L’Hospitalet del Llobregat, Spain

11. Statistics Department, Universidad de Salamanca, Salamanca, Spain

12. Hematology Department, Hospital Universitario de Canarias, La Laguna, Spain

13. Hematology Department, Hospital Universitario Vall d’Hebron, Barcelona, Spain

14. Hematology Department, Hospital Arnau de Vilanova, Valencia, Spain

15. Hematology Department, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Spain

16. Hematology Department, Hospital Universitario Infanta Leonor, Madrid, Spain

17. Hematology Department, Hospital Virgen de la Luz, Cuenca, Spain

18. Instituto de Biología Molecular y Celular del Cáncer, Instituto Biosanitario de Salamanca, Centro de Investigación del Cáncer, USAL-CSIC, Salamanca, Spain Hematology Department, Hospital Universitario de Salamanca, Salamanca, Spain Instituto Biosanitario de Salamanca, Salamanca, Spain

19. Hematology Department, Hospital Universitario de Salamanca, Salamanca, Spain Instituto Biosanitario de Salamanca, Salamanca, Spain

20. Instituto Biosanitario de Salamanca, Salamanca, Spain

21. Hematology Department, Hospital Universitario de Salamanca, Paseo de San Vicente 58-182, Salamanca 37007, Spain

Abstract

Background: Erythropoiesis stimulating agents (ESAs) are the first-line therapy in patients with lower-risk myelodysplastic syndromes (LR-MDS). Some predictive factors for ESAs response have been identified. Type and number of somatic mutations have been associated with prognosis and response to therapies in MDS patients. Objectives: The objective was to evaluate the outcomes after ESAs in patients with LR-MDS and to address the potential predictive value of somatic mutations in ESAs-treated patients. Design: Multi-center retrospective study of a cohort of 722 patients with LR-MDS included in the SPRESAS (Spanish Registry of Erythropoietic Stimulating Agents Study) study. Retrospective analysis of 65 patients with next generation sequencing (NGS) data from diagnosis. Methods: ESAs’ efficacy and safety were evaluated in patients receiving ESAs and best supportive care (BSC). To assess the potential prognostic value of somatic mutations in erythroid response (ER) rate and outcome, NGS was performed in responders and non-responders. Results: ER rate for ESAs-treated patients was 65%. Serum erythropoietin (EPO) level <200 U/l was the only variable significantly associated with a higher ER rate (odds ratio, 2.45; p = 0.036). Median overall survival (OS) in patients treated with ESAs was 6.7 versus 3.1 years in patients receiving BSC ( p < 0.001). From 65 patients with NGS data, 57 (87.7%) have at least one mutation. We observed a trend to a higher frequency of ER among patients with a lower number of mutated genes (40.4% in <3 mutated genes versus 22.2% in ⩾3; p = 0.170). The presence of ⩾3 mutated genes was also significantly associated with worse OS (hazard ratio, 2.8; p = 0.015), even in responders. A higher cumulative incidence of acute myeloid leukemia progression at 5 years was also observed in patients with ⩾3 mutated genes versus <3 (33.3% and 10.7%, respectively; p < 0.001). Conclusion: This large study confirms the beneficial effect of ESAs and the adverse effect of somatic mutations in patients with LR-MDS.

Publisher

SAGE Publications

Subject

Hematology

Link

http://journals.sagepub.com/doi/pdf/10.1177/20406207231218157

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