(1) Background: The combination of venetoclax and hypomethylating agents (HMAs) is a standard first-line regimen for acute myeloid leukemia (AML) patients unfit for intensive chemotherapy. Since venetoclax-HMAs are usually administered until progression and delayed hematologic recovery is one of the limiting toxicities, cyclic administration including 7–14-day breaks is recommended. However, whether longer venetoclax schedules lead to higher response rates and how venetoclax pharmacokinetics correlate with toxicity and efficacy remains unclarified. In this single-center retrospective study, we analyzed how venetoclax plasma levels and treatment duration impact hematologic toxicity and treatment responses. (2) Methods: We analyzed the safety and efficacy of venetoclax-HMA combination regimens in a cohort of AML patients unfit for intensive chemotherapy treated at our institution between June 2020 and September 2023. The primary endpoint was the correlation between venetoclax plasma levels or administration schedule with hematologic recovery after the first cycle. Secondary endpoints included the following clinical outcomes: correlation with complete response (CR) status, progression-free survival, and overall survival. (3) Results: Within our cohort of 75 AML patients, we found no correlation between venetoclax plasma peak and trough levels, or venetoclax treatment duration (≤ or >14 days), and hematologic toxicity. Patients receiving shorter venetoclax schedules (≤14 days) had similar CR rates compared to patients treated with longer schedules. (4) Conclusions: Our results suggest that shorter (≤14 days) venetoclax schedules may have no negative impact on tumor responses in AML patients receiving venetoclax and HMA combinations. However, prospective validation studies would be required to confirm these findings.
（1）背景：维奈克拉联合去甲基化药物（HMAs）是不适合强化化疗的急性髓系白血病（AML）患者的标准一线治疗方案。由于维奈克拉-HMAs通常需持续给药至疾病进展，而延迟的血液学恢复是限制性毒性之一，因此推荐采用包含7-14天间歇期的周期性给药方案。然而，更长的维奈克拉给药周期是否会导致更高的缓解率，以及维奈克拉药代动力学参数与毒性及疗效的相关性尚未明确。本单中心回顾性研究旨在分析维奈克拉血药浓度及治疗持续时间对血液学毒性和治疗反应的影响。（2）方法：我们分析了2020年6月至2023年9月期间在本机构接受治疗、不适合强化化疗的AML患者队列中维奈克拉-HMA联合方案的安全性和有效性。主要终点是维奈克拉血药浓度或给药方案与第一周期后血液学恢复的相关性。次要终点包括以下临床结局：与完全缓解（CR）状态的相关性、无进展生存期和总生存期。（3）结果：在75例AML患者队列中，我们发现维奈克拉血药峰浓度和谷浓度、或维奈克拉治疗持续时间（≤14天或>14天）与血液学毒性无相关性。接受较短维奈克拉给药周期（≤14天）的患者与接受较长周期治疗的患者相比，完全缓解率相似。（4）结论：我们的研究结果表明，在接受维奈克拉和HMA联合治疗的AML患者中，较短（≤14天）的维奈克拉给药周期可能不会对肿瘤反应产生负面影响。然而，这些发现仍需前瞻性验证研究加以证实。
肿瘤(癌症)患者之家