To investigate the efficacy and toxicities of CPX-351 outside a clinical trial, we analyzed 188 patients (median age 65 years, range 26–80) treated for therapy-related acute myeloid leukemia (t-AML, 29%) or AML with myelodysplasia-related changes (AML-MRC, 70%). Eighty-six percent received one, 14% two induction cycles, and 10% received consolidation (representing 22% of patients with CR/CRi) with CPX-351. Following induction, CR/CRi rate was 47% including 64% of patients with available information achieving measurable residual disease (MRD) negativity (<10⁻³) as measured by flow cytometry. After a median follow-up of 9.3 months, median overall survival (OS) was 21 months and 1-year OS rate 64%. In multivariate analysis, complex karyotype predicted lower response (p = 0.0001), while pretreatment with hypomethylating agents (p = 0.02) and adverse European LeukemiaNet 2017 genetic risk (p < 0.0001) were associated with lower OS. Allogeneic hematopoietic cell transplantation (allo-HCT) was performed in 116 patients (62%) resulting in promising outcome (median survival not reached, 1-year OS 73%), especially in MRD-negative patients (p = 0.048). With 69% of patients developing grade III/IV non-hematologic toxicity following induction and a day 30-mortality of 8% the safety profile was consistent with previous findings. These real-world data confirm CPX-351 as efficient treatment for these high-risk AML patients facilitating allo-HCT in many patients with promising outcome after transplantation.

为了研究 CPX-351 在临床试验之外的疗效和毒性，我们分析了 188 名接受治疗相关的急性髓性白血病（t-AML，29%）或伴有骨髓增生异常的 AML 的患者（中位年龄 65 岁，范围 26-80）相关变化（AML-MRC，70%）。86% 接受了一个诱导周期，14% 接受了两个诱导周期，10% 接受了 CPX-351 巩固治疗（占 CR/CRi 患者的 22%）。诱导后，CR/CRi 率为 47%，包括 64% 的可用信息实现可测量残留病 (MRD) 阴性 (<10 ^-3 ) 的患者，通过流式细胞术测量。中位随访 9.3 个月后，中位总生存期 (OS) 为 21 个月，1 年 OS 率为 64%。在多变量分析中，复杂核型预测较低的反应（p = 0.0001），而低甲基化药物预处理（p  = 0.02）和不利的欧洲白血病网络 2017 遗传风险（p  < 0.0001）与较低的 OS 相关。116 名患者 (62%) 接受了异基因造血细胞移植 (allo-HCT)，结果令人鼓舞（未达到中位生存期，1 年 OS 为 73%），尤其是在 MRD 阴性患者中（p  = 0.048）。69% 的患者在诱导后出现 III/IV 级非血液学毒性，30 天死亡率为 8%，安全性与之前的研究结果一致。这些真实世界的数据证实 CPX-351 可有效治疗这些高危 AML 患者，促进许多患者移植后有希望的结果的 allo-HCT。