CPX-351 (United States: Vyxeos®; Europe: Vyxeos® Liposomal), a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio, is approved by the US FDA and the EMA for the treatment of adults with newly diagnosed therapy-related acute myeloid leukemia or acute myeloid leukemia with myelodysplasia-related changes. In a pivotal phase 3 study that evaluated 309 patients aged 60 to 75 years with newly diagnosed high-risk/secondary acute myeloid leukemia, CPX-351 significantly improved median overall survival versus conventional 7 + 3 chemotherapy (cytarabine continuous infusion for 7 days plus daunorubicin for 3 days), with a comparable safety profile. A Quality‐adjusted Time Without Symptoms of disease or Toxicity (Q-TWiST) analysis of the phase 3 study was performed to compare survival quality between patients receiving CPX-351 versus conventional 7 + 3 after 5 years of follow-up. Patients were randomized 1:1 between December 20, 2012 and November 11, 2014 to receive induction with CPX-351 or 7 + 3. Survival time for each patient was partitioned into 3 health states: TOX (time with any grade 3 or 4 toxicity or prior to remission), TWiST (time in remission without relapse or grade 3 or 4 toxicity), and REL (time after relapse). Within each treatment arm, Q-TWiST was calculated by adding the mean time spent in each health state weighted by its respective quality-of-life, represented by health utility. The relative Q-TWiST gain, calculated as the difference in Q-TWiST between treatment arms divided by the mean survival of the 7 + 3 control arm, was determined in order to evaluate results in the context of other Q-TWiST analyses. The relative Q-TWiST gain with CPX-351 versus 7 + 3 was 53.6% in the base case scenario and 39.8% among responding patients. Across various sensitivity analyses, the relative Q-TWiST gains for CPX-351 ranged from 48.0 to 57.6%, remaining well above the standard clinically important difference threshold of 15% for oncology. This post hoc analysis demonstrates that CPX-351 improved quality-adjusted survival, further supporting the clinical benefit in patients with newly diagnosed high-risk/secondary acute myeloid leukemia. Trial registration This trial was registered on September 28, 2012 at www.clinicaltrials.gov as NCT01696084 ( https://clinicaltrials.gov/ct2/show/NCT01696084 ) and is complete.

中文翻译：

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新诊断的高危/继发性 AML 老年人中 CPX-351 与 7 + 3 的质量调整时间无疾病或毒性症状 (Q-TWiST) 分析

CPX-351（美国：Vyxeos®；欧洲：Vyxeos®脂质体）是柔红霉素和阿糖胞苷以 1:5 摩尔比协同包封的双药脂质体，已获得美国 FDA 和 EMA 批准用于成人治疗与新诊断的治疗相关的急性髓系白血病或伴有骨髓增生异常相关变化的急性髓系白血病。在一项评估了 309 名 60 至 75 岁新诊断高危/继发性急性髓系白血病患者的关键 3 期研究中，CPX-351 与常规 7 + 3 化疗（阿糖胞苷连续输注 7 天加柔红霉素）相比显着提高了中位总生存期3 天），具有相当的安全性。对 3 期研究进行了质量调整时间无疾病或毒性症状 (Q-TWiST) 分析，以比较接受 CPX-351 与常规 7 + 3 的患者在 5 年随访后的生存质量。在 2012 年 12 月 20 日至 2014 年 11 月 11 日期间，患者按 1:1 随机分组接受 CPX-351 或 7+3 诱导。每位患者的生存时间分为 3 种健康状态：TOX（任何 3 级或 4 级毒性的时间）或缓解前）、TWiST（无复发或 3 或 4 级毒性的缓解时间）和 REL（复发后时间）。在每个治疗组中，Q-TWiST 是通过将每个健康状态花费的平均时间相加来计算的，这些时间由其各自的生活质量加权，由健​​康效用表示。相对 Q-TWiST 增益，计算为治疗组之间 Q-TWiST 的差异除以 7 + 3 控制组的平均存活率，是为了在其他 Q-TWiST 分析的背景下评估结果。CPX-351 与 7 + 3 的相对 Q-TWiST 增益在基本情况下为 53.6%，在响应患者中为 39.8%。在各种敏感性分析中，CPX-351 的相对 Q-TWiST 增益范围为 48.0% 至 57.6%，远高于肿瘤学标准临床重要差异阈值 15%。这项事后分析表明 CPX-351 提高了质量调整生存率，进一步支持了新诊断的高危/继发性急性髓系白血病患者的临床获益。试验注册 本试验于 2012 年 9 月 28 日在 www.clinicaltrials.gov 注册为 NCT01696084 ( https: