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
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Type and number of somatic mutations have been associated with prognosis and response to therapies in MDS patients.</p><p><strong>Objectives: </strong>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.</p><p><strong>Design: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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; <i>p</i> = 0.036). Median overall survival (OS) in patients treated with ESAs was 6.7 <i>versus</i> 3.1 years in patients receiving BSC (<i>p</i> < 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 <i>versus</i> 22.2% in ⩾3; <i>p</i> = 0.170). The presence of ⩾3 mutated genes was also significantly associated with worse OS (hazard ratio, 2.8; <i>p</i> = 0.015), even in responders. 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引用次数: 0
摘要
背景：促红细胞生成素（ESAs）是低风险骨髓增生异常综合征（LR-MDS）患者的一线疗法。目前已发现一些预测ESAs反应的因素。体细胞突变的类型和数量与MDS患者的预后和治疗反应有关：目的：评估LR-MDS患者接受ESAs治疗后的预后，并探讨体细胞突变对ESAs治疗患者的潜在预测价值：对SPRESAS（西班牙促红细胞生成素注册研究）研究中的722名LR-MDS患者进行多中心回顾性研究。回顾性分析了65例患者的诊断结果和新一代测序（NGS）数据：对接受 ESAs 和最佳支持治疗 (BSC) 的患者进行 ESAs 疗效和安全性评估。为了评估体细胞突变在红细胞反应（ER）率和预后中的潜在预后价值，对反应者和非反应者进行了 NGS 测序：结果：ESAs治疗患者的红细胞生成率为65%。血清促红细胞生成素（EPO）水平 p = 0.036）。接受ESAs治疗的患者中位总生存期（OS）为6.7年，而接受BSC治疗的患者中位总生存期为3.1年（⩾3患者中位总生存期为6.7年，而⩾3患者中位总生存期为22.2%；P = 0.170）。⩾3突变基因的存在也与较差的OS显著相关（危险比为2.8；p = 0.015），即使在应答者中也是如此。在基因⩾3突变的患者中，还观察到5年后急性髓性白血病进展的累积发生率高于基因⩾3突变的患者：这项大型研究证实了ESAs对LR-MDS患者的益处以及体细胞突变的不利影响。
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 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.
期刊介绍：
Therapeutic Advances in Hematology delivers the highest quality peer-reviewed articles, reviews, and scholarly comment on pioneering efforts and innovative studies across all areas of hematology. The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in hematology, providing a forum in print and online for publishing the highest quality articles in this area.
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