Gonzalez-Lugo Jesus D, Kambhampati Suman, Yacoub Abdulraheem, Donnellan William B, Berdeja Jesus, Bhagat Prafulla, Fehn Karen, Remy Cassady, Jasra Sakshi, Kazemi Mohammed, Pradhan Kith, Kim Mimi, Mantzaris Ioannis, Sica R Alejandro, Shah Nishi, Goldfinger Mendel, Kornblum Noah, Gritsman Kira, Braunschweig Ira, Steidl Ulrich, Will Britta, Shastri Aditi, Verma Amit
Division of Hemato-Oncology, Department of Oncology, Montefiore Einstein Cancer Center, Blood Cancer Institute, Bronx, New York.
Sarah Cannon Transplant and Cellular Therapy Program, Kansas City, Kansas.
Clin Cancer Res. 2023 Jan 4;29(1):60-66. doi: 10.1158/1078-0432.CCR-22-1457.
Thrombocytopenia is a serious complication of myelodysplastic syndromes (MDS) associated with an increased bleeding risk and worse prognosis. Eltrombopag (ELT), a thrombopoietin receptor agonist, can increase platelet counts and reverse anti-megakaryopoietic effects of lenalidomide (LEN) in preclinical studies. We hypothesized ELT would reduce the incidence of thrombocytopenia in MDS.
We conducted a Phase II multicenter trial of ELT and LEN in adult patients with low- or intermediate-1-risk MDS with symptomatic or transfusion-dependent anemia or thrombocytopenia (NCT01772420). Thrombocytopenic patients were started on ELT and subsequently treated with LEN after platelets were increased. Patients without thrombocytopenia were started on LEN monotherapy and treated with ELT if they became thrombocytopenic.
Fifty-two patients were enrolled; mean age was 71 years (range 34-93). Overall response rate (ORR) in the intention-to-treat population was 35% (18/52). ELT monotherapy led to ORR of 33.3% (7/21), 29% achieving hematologic improvement (HI)-Platelets, and 24% bilineage responses. LEN monotherapy had 38% ORR (6/16) with all responders achieving HI-Erythroid. Fifteen patients received both ELT and LEN with ORR of 33.3%, 20% achieved HI-Erythroid, and 20% HI-Platelets with 13% bilineage responses. Median duration of response was 40 weeks for ELT (range 8-ongoing), 41 weeks (25-ongoing) for LEN, and 88 weeks (8.3-ongoing) for ELT/LEN. Non-hematologic grade 3-4 treatment-related adverse events were infrequent. Among patients on ELT, 2 had major bleeding events, 1 had a reversible increase in peripheral blasts, and 1 developed marrow fibrosis after 6 years on ELT.
ELT and LEN are well tolerated and effective in achieving hematologic improvement in patients with low-/intermediate-risk MDS.
血小板减少是骨髓增生异常综合征（MDS）的严重并发症，与出血风险增加及预后较差相关。艾曲泊帕（ELT）是一种血小板生成素受体激动剂，在临床前研究中可增加血小板计数并逆转来那度胺（LEN）的抗巨核细胞生成作用。我们推测ELT可降低MDS患者血小板减少的发生率。
我们对有症状性或输血依赖型贫血或血小板减少的低危或中危-1 MDS成年患者进行了一项ELT与LEN的II期多中心试验（NCT01772420）。血小板减少的患者开始使用ELT治疗，血小板增加后再接受LEN治疗。无血小板减少的患者开始接受LEN单药治疗，若出现血小板减少则接受ELT治疗。
共纳入52例患者；平均年龄71岁（范围34 - 93岁）。意向性治疗人群的总缓解率（ORR）为35%（18/52）。ELT单药治疗的ORR为33.3%（7/21），29%达到血液学改善（HI）-血小板，24%为双系反应。LEN单药治疗的ORR为38%（6/16），所有缓解者均达到HI-红细胞。15例患者接受了ELT和LEN联合治疗，ORR为33.3%，20%达到HI-红细胞，20%达到HI-血小板，13%为双系反应。ELT的中位缓解持续时间为40周（范围8 - 持续），LEN为41周（25 - 持续），ELT/LEN为88周（8.3 - 持续）。非血液学3 - 4级治疗相关不良事件不常见。接受ELT治疗的患者中，2例发生严重出血事件，1例外周血原始细胞可逆性增加，1例在接受ELT治疗6年后发生骨髓纤维化。
ELT和LEN耐受性良好，在实现低危/中危MDS患者血液学改善方面有效。
