Outcomes and effect of somatic mutations after erythropoiesis stimulating agents in patients with lower-risk myelodysplastic syndromes
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 the...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2024-01-01
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| Series: | Therapeutic Advances in Hematology |
| Online Access: | https://doi.org/10.1177/20406207231218157 |
| _version_ | 1797366078763958272 |
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| author | Juan Carlos Caballero Julio Dávila María López-Pavía Esperanza Such Teresa Bernal Fernando Ramos Marisa Calabuig Jesús María Hernández Sánchez Helena Pomares Mercedes Sánchez Barba María Abáigar Bernardo González Brayan Merchán Reyes Sancho-Tello Marta Callejas Carolina Muñoz-Novas Carlos Cerveró Guillermo Sanz Jesús María Hernández Rivas María Díez Campelo; |
| author_facet | Juan Carlos Caballero Julio Dávila María López-Pavía Esperanza Such Teresa Bernal Fernando Ramos Marisa Calabuig Jesús María Hernández Sánchez Helena Pomares Mercedes Sánchez Barba María Abáigar Bernardo González Brayan Merchán Reyes Sancho-Tello Marta Callejas Carolina Muñoz-Novas Carlos Cerveró Guillermo Sanz Jesús María Hernández Rivas María Díez Campelo; |
| author_sort | Juan Carlos Caballero |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T16:59:07Z |
| format | Article |
| id | doaj.art-aae5bf162b0d4831a1ded6c9dd145238 |
| institution | Directory Open Access Journal |
| issn | 2040-6215 |
| language | English |
| last_indexed | 2024-03-08T16:59:07Z |
| publishDate | 2024-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Therapeutic Advances in Hematology |
| spelling | doaj.art-aae5bf162b0d4831a1ded6c9dd1452382024-01-04T16:03:44ZengSAGE PublishingTherapeutic Advances in Hematology2040-62152024-01-011510.1177/20406207231218157Outcomes and effect of somatic mutations after erythropoiesis stimulating agents in patients with lower-risk myelodysplastic syndromesJuan Carlos CaballeroJulio DávilaMaría López-PavíaEsperanza SuchTeresa BernalFernando RamosMarisa CalabuigJesús María Hernández SánchezHelena PomaresMercedes Sánchez BarbaMaría AbáigarBernardo GonzálezBrayan MerchánReyes Sancho-TelloMarta CallejasCarolina Muñoz-NovasCarlos CerveróGuillermo SanzJesús María Hernández RivasMaría Díez Campelo;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.https://doi.org/10.1177/20406207231218157 |
| spellingShingle | Juan Carlos Caballero Julio Dávila María López-Pavía Esperanza Such Teresa Bernal Fernando Ramos Marisa Calabuig Jesús María Hernández Sánchez Helena Pomares Mercedes Sánchez Barba María Abáigar Bernardo González Brayan Merchán Reyes Sancho-Tello Marta Callejas Carolina Muñoz-Novas Carlos Cerveró Guillermo Sanz Jesús María Hernández Rivas María Díez Campelo; Outcomes and effect of somatic mutations after erythropoiesis stimulating agents in patients with lower-risk myelodysplastic syndromes Therapeutic Advances in Hematology |
| title | Outcomes and effect of somatic mutations after erythropoiesis stimulating agents in patients with lower-risk myelodysplastic syndromes |
| title_full | Outcomes and effect of somatic mutations after erythropoiesis stimulating agents in patients with lower-risk myelodysplastic syndromes |
| title_fullStr | Outcomes and effect of somatic mutations after erythropoiesis stimulating agents in patients with lower-risk myelodysplastic syndromes |
| title_full_unstemmed | Outcomes and effect of somatic mutations after erythropoiesis stimulating agents in patients with lower-risk myelodysplastic syndromes |
| title_short | Outcomes and effect of somatic mutations after erythropoiesis stimulating agents in patients with lower-risk myelodysplastic syndromes |
| title_sort | outcomes and effect of somatic mutations after erythropoiesis stimulating agents in patients with lower risk myelodysplastic syndromes |
| url | https://doi.org/10.1177/20406207231218157 |
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