CPX-351 in Down syndrome-associated myeloid leukemia: results and prognostic factors from the phase 3 ML-DS 2018 trial.

The Phase 3 Clinical Trial for CPX-351 in ML-DS 2018 aimed to maintain the excellent event-free survival (EFS) achieved in the previous ML-DS 2006 trial while reducing the treatment intensity.

2018年针对CPX-351在ML-DS中的III期临床试验旨在维持2006年ML-DS试验中取得的极佳无事件生存（EFS）率，同时降低治疗强度。

Intensity-reduced induction and reinduction therapy with cytarabine and idarubicin with or without etoposide was replaced with CPX-351 (66 U/m2 on 3 days in course 1 and on 2 days in course 2).

低强度的阿糖胞苷和伊达比星诱导和再诱导治疗，有或没有依托泊苷，已被CPX-351（第1疗程3天，每天66 U/m2，第2疗程2天）所取代。

Risk stratification was based on flow cytometric measurable residual disease (MRD) after first induction.

风险分层基于第一次诱导后流式细胞术可测量的残留疾病（MRD）。

High-risk patients received high-dose cytarabine (3 g/m2 per 12 hour) in consolidation; standard-risk patients received cytarabine at a dose of 1 g/m2 per 12 hour.

高危患者在巩固治疗中接受了高剂量的阿糖胞苷（每12小时3克/平方米）；标准风险患者接受的阿糖胞苷剂量为每12小时1克/平方米。

A total of 35 patients were enrolled until the trial was halted because of an unexpectedly high relapse rate.

共有35名患者被纳入试验，直至试验因意外高复发率而被停止。

A per-protocol interim analysis revealed a significantly lower 24-month EFS when compared with the ML-DS 2006 trial (69% vs 90%; P< .001).

按方案的中期分析显示，与ML-DS 2006试验相比，24个月无事件生存率显著降低（69%对比90%；P< .001）。

In contrast with previous studies, most patients who relapsed responded to salvage therapy, leading to a comparable 24-month overall survivalof 88% (vs 92%; P = .612).

与以往的研究形成对比，大多数复发患者对挽救治疗有反应，导致24个月总生存率相当，为88%（对比92%；P = .612）。

CPX-351 demonstrated a favorable toxicity profile with no treatment-related mortality.

CPX-351 展现出良好的毒性特征，无治疗相关死亡事件。

Positive MRD by error-corrected GATA1 next-generation sequencing, the presence of trisomy 8 or a complex karyotype were associated with an increased risk for relapse.

通过误差校正的 GATA1 下一代测序（NGS）检测到的微小残留病灶（MRD）阳性，以及三体8或复杂核型的存在，与复发风险增加相关。

In conclusion, replacing intensity-reduced induction therapy with CPX-351 in ML-DS led to a significantly lower EFS, highlighting the need for dose optimization to balance the efficacy and toxicity in this sensitive patient population.

总之，在ML-DS中，用CPX-351替代强度降低的诱导治疗导致了显著较低的无事件生存率(EFS)，这突显了在这一敏感患者群体中需要进行剂量优化以平衡疗效和毒性。

This trial was registered at https://www.clinicaltrialsregister.eu as EudraCT #2018-002988-25.

该试验已在https://www.clinicaltrialsregister.eu 注册，注册号为EudraCT #2018-002988-25。