Abstract：
Failure after hypomethylating agents (HMAs) is associated with dismal outcomes in higher risk myelodysplastic syndromes (HR-MDS) or chronic myelomonocytic leukaemia (CMML). We aimed to evaluate the safety and preliminary activity of lower doses of CPX-351, a liposomal encapsulation of cytarabine and daunorubicin, in a single-centre, phase 1/2 study for patients with HR-MDS or CMML after HMA failure. Four doses of CPX-351 (10, 25, 50 and 75 units/m2 ) administered on Days 1, 3 and 5 of induction and Days 1 and 3 of consolidation were evaluated. Between June 2019 and June 2023, 25 patients were enrolled (phase 1: n = 15; phase 2: n = 10) including 19 (76%) with HR-MDS and 6 (24%) with CMML. Most common grade 3-4 non-haematological treatment-emergent adverse events were febrile neutropenia (n = 12, 48%) and lung infection (n = 5, 20%). Three patients (age >75) experienced cardiac toxicity at the 75 units/m2 dose. Further enrolment continued at 50 units/m2 . Four- and 8-week mortality were 0% and 8% respectively. The overall response rate was 56% with median relapse-free and overall survivals of 9.2 (95% CI 3.2-15.1 months) and 8.7 months (95% CI 1.8-15.6 months) respectively. These data suggest that lower doses of CPX-351 are safe. Further studies are needed to evaluate its activity.
摘要：
低甲基化药物（HMA）后失败与高风险骨髓增生异常综合征（HR-MDS）或慢性粒单核细胞白血病（CMML）的不良结局相关。我们旨在评估较低剂量的CPX-351的安全性和初步活性，CPX-351是阿糖胞苷和柔红霉素的脂质体封装，在单中心，HMA失败后HR-MDS或CMML患者的1/2期研究。评价在诱导的第1、3和5天以及巩固的第1和3天施用的4个剂量的CPX-351(10、25、50和75单位/m2)。在2019年6月至2023年6月之间，招募了25例患者（1期：n=15；2期：n=10），其中19例（76％）患有HR-MDS，6例（24％）患有CMML。最常见的3-4级非血液学治疗引起的不良事件是发热性中性粒细胞减少症（n=12，48％）和肺部感染（n=5，20％）。三名患者(年龄>75)在75单位/m2剂量下经历心脏毒性。继续以50个单位/平方米的速度继续招生。4周和8周死亡率分别为0%和8%。总有效率为56%，中位无复发和总生存率分别为9.2个月（95%CI3.2-15.1个月）和8.7个月（95%CI1.8-15.6个月）。这些数据表明较低剂量的CPX-351是安全的。需要进一步的研究来评估其活性。
