Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jan 4:15:20406207231218157.
doi: 10.1177/20406207231218157. eCollection 2024.

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

Juan Carlos Caballero  1 , Julio Dávila  2 , María López-Pavía  3   4   5 , Esperanza Such  3   4   5 , Teresa Bernal  6 , Fernando Ramos  7 , Marisa Calabuig  8 , Jesús María Hernández Sánchez  9 , Helena Pomares  10 , Mercedes Sánchez Barba  11 , María Abáigar  9 , Bernardo González  12 , Brayan Merchán  13 , Reyes Sancho-Tello  14 , Marta Callejas  15 , Carolina Muñoz-Novas  16 , Carlos Cerveró  17 , Guillermo Sanz  3   4   5 , Jesús María Hernández Rivas  18   19   20 , María Díez Campelo  21   20
Affiliations

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

Juan Carlos Caballero et al. Ther Adv Hematol. .

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.

Keywords: erythropoiesis stimulating agents; lower-risk myelodysplastic syndromes; myelodysplastic syndromes; next generation sequencing; somatic mutations.

PubMed Disclaimer

Conflict of interest statement

The authors declare that there is no conflict of interest.

Figures

Figure 1.
Figure 1.
Overall survival in SPRESAS study according to the management strategy: best supportive care versus ESAs treatment (landmark analysis). ESA, erythropoiesis stimulating agents; SPRESAS, Spanish Registry of Erythropoietic Stimulating Agents Study.
Figure 2.
Figure 2.
Overall survival from ESAs onset in SPRESAS study according to erythroid response. ESA, erythropoiesis stimulating agents; SPRESAS, Spanish Registry of Erythropoietic Stimulating Agents Study.
Figure 3.
Figure 3.
Patients with LR-MDS treated with ESAs: somatic mutations and cytogenetics. ESA, erythropoiesis stimulating agents; LR-MDS, lower-risk myelodysplastic syndromes.
Figure 4.
Figure 4.
Erythroid response according to the number of mutated genes.
Figure 5.
Figure 5.
Overall survival: entire cohort (a) and according to the number of mutated genes (b), SRSF2 mutational status (c), and STAG2 mutational status (d).
Figure 6.
Figure 6.
Cumulative incidence of acute myeloid leukemia: entire cohort (a), according to the number of mutated genes (b), and according to STAG2 mutational status (c).
See this image and copyright information in PMC

References

    1. Greenberg P, Cox C, LeBeau MM, et al.. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997; 89: 2079–2088. - PubMed
    1. Greenberg PL, Tuechler H, Schanz J, et al.. Revised International Prognostic Scoring System for myelodysplastic syndromes. Blood 2012; 120: 2454–2465. - PMC - PubMed
    1. Park S, Grabar S, Kelaidi C, et al.. Predictive factors of response and survival in myelodysplastic syndrome treated with erythropoietin and G-CSF: the GFM experience. Blood 2008; 111: 574–582. - PubMed
    1. Santini V, Schemenau J, Levis A, et al.. Can the revised IPSS predict response to erythropoietic-stimulating agents in patients with classical IPSS low or intermediate-1 MDS? Blood 2013; 122: 2286–2288. - PubMed
    1. Houston BL, Jayakar J, Wells RA, et al.. A predictive model of response to erythropoietin stimulating agents in myelodysplastic syndrome: from the Canadian MDS patient registry. Ann Hematol 2017; 96: 2025–2029. - PubMed