Fattizzo Bruno, Versino Francesco, Bortolotti Marta, Rizzo Lorenzo, Riva Marta, Barcellini Wilma
Hematology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Department of Oncology and Oncohematology, University of Milan, Milan, Italy.
Eur J Haematol. 2023 May;110(5):571-574. doi: 10.1111/ejh.13933. Epub 2023 Feb 12.
Patients with myelodysplastic syndromes and ring sideroblasts (MDS RS) are clinically characterized by severe anemia and transfusion need. Erythropoiesis-stimulating agents (ESAs), which stimulate hemoglobin production and early maturation of erythroid precursors, are effective only in a portion of patients and for limited time. Luspatercept, an inhibitor of the TGF-beta pathway, is beneficial in unblocking late-stage erythropoiesis and has been approved for MDS RS patients failing or not-candidate to ESAs. ESAs and/or luspatercept failure represents an unmet clinical need and most patients become life-long transfusion dependent. Here, we describe the clinical combination of luspatercept with ESAs (subcutaneous epoetin alpha 40-80 000 IU/week) in seven MDS RS patients. Two patients had ESAs as pre-existing therapy, while five were re-challenged with ESAs as add-on treatment due to luspatercept failure. Three patients achieved hematologic improvement, and one became transfusion independent. No adverse events were noted. This is the first clinical evidence that stimulating both early and late-stage erythropoiesis may offer a further option for this challenging patient population.
伴有环形铁粒幼细胞的骨髓增生异常综合征（MDS RS）患者的临床特征为严重贫血且需要输血。促红细胞生成剂（ESAs）可刺激血红蛋白生成及红系前体细胞的早期成熟，但仅对部分患者在有限时间内有效。Luspatercept是一种转化生长因子-β（TGF-β）通路抑制剂，有助于解除晚期红细胞生成障碍，已被批准用于对ESAs治疗无效或不适用的MDS RS患者。ESAs和/或Luspatercept治疗失败代表了一种未满足的临床需求，大多数患者会终身依赖输血。在此，我们描述了Luspatercept与ESAs（皮下注射促红细胞生成素α 40 - 80000 IU/周）联合应用于7例MDS RS患者的临床情况。2例患者之前已接受ESAs治疗，另外5例因Luspatercept治疗失败而重新接受ESAs作为附加治疗。3例患者实现了血液学改善，1例不再依赖输血。未观察到不良事件。这是首个临床证据，表明刺激早期和晚期红细胞生成可能为这一具有挑战性的患者群体提供进一步的治疗选择。
