PDF(Pubmed)
Abstract：
BACKGROUND: In a Phase 3 international clinical trial (VIALE-C), venetoclax plus low-dose cytarabine improved the response rate and overall survival versus placebo plus low-dose cytarabine in patients with newly diagnosed acute myeloid leukemia who were ineligible for intensive chemotherapy. After the enrollment period of VIALE-C ended, we conducted an expanded access study to provide preapproval access to venetoclax in combination with low-dose cytarabine in Japan.
METHODS: Previously, untreated patients with acute myeloid leukemia who were ineligible for intensive chemotherapy were enrolled according to the VIALE-C criteria. Patients received venetoclax (600 mg, Days 1-28, 4-day ramp-up in Cycle 1) in 28-day cycles and low-dose cytarabine (20 mg/m2, Days 1-10). All patients took tumor lysis syndrome prophylactic agents and hydration. Safety endpoints were assessed.
RESULTS: Fourteen patients were enrolled in this study. The median age was 77.5 years (range = 61-84), with 78.6% over 75 years old. The most common grade ≥ 3 treatment-emergent adverse event was neutropenia (57.1%). Febrile neutropenia was the most frequent serious adverse event (21.4%). One patient developed treatment-related acute kidney injury, leading to discontinuation of treatment. Two patients died because of cardiac failure and disease progression that were judged not related to study treatment. No patients developed tumor lysis syndrome.
CONCLUSIONS: The safety outcomes were similar to those in VIALE-C without new safety signals and were well managed with standard medical care. In clinical practice, more patients with severe background disease are expected, in comparison with in VIALE-C, suggesting that it is important to carefully manage and prevent adverse events.
METHODS: Previously, untreated patients with acute myeloid leukemia who were ineligible for intensive chemotherapy were enrolled according to the VIALE-C criteria. Patients received venetoclax (600 mg, Days 1-28, 4-day ramp-up in Cycle 1) in 28-day cycles and low-dose cytarabine (20 mg/m2, Days 1-10). All patients took tumor lysis syndrome prophylactic agents and hydration. Safety endpoints were assessed.
RESULTS: Fourteen patients were enrolled in this study. The median age was 77.5 years (range = 61-84), with 78.6% over 75 years old. The most common grade ≥ 3 treatment-emergent adverse event was neutropenia (57.1%). Febrile neutropenia was the most frequent serious adverse event (21.4%). One patient developed treatment-related acute kidney injury, leading to discontinuation of treatment. Two patients died because of cardiac failure and disease progression that were judged not related to study treatment. No patients developed tumor lysis syndrome.
CONCLUSIONS: The safety outcomes were similar to those in VIALE-C without new safety signals and were well managed with standard medical care. In clinical practice, more patients with severe background disease are expected, in comparison with in VIALE-C, suggesting that it is important to carefully manage and prevent adverse events.
摘要：
背景：在3期国际临床试验（VIALE-C）中，与安慰剂+低剂量阿糖胞苷相比,维奈托克联合低剂量阿糖胞苷改善了新诊断的急性髓系白血病患者的缓解率和总生存期,这些患者不适合接受强化化疗.在VIALE-C的注册期结束后，我们在日本进行了一项扩大的准入研究,以提供维奈托克联合低剂量阿糖胞苷的预批准准入.
方法：以前，根据VIALE-C标准纳入不符合强化化疗条件的未经治疗的急性髓系白血病患者.患者接受维奈托克（600毫克，第1-28天，第1周期中的4天增加），28天周期和低剂量阿糖胞苷（20mg/m2，第1-10天）。所有患者均服用肿瘤溶解综合征预防剂和水合剂。评估安全性终点。
结果：本研究纳入了14例患者。中位年龄为77.5岁（范围=61-84），78.6%超过75岁。最常见的≥3级治疗引起的不良事件是中性粒细胞减少症（57.1％）。发热性中性粒细胞减少是最常见的严重不良事件（21.4%）。一名患者出现了治疗相关的急性肾损伤，导致停止治疗。两名患者因心力衰竭和疾病进展而死亡，被认为与研究治疗无关。无患者出现肿瘤溶解综合征。
结论：安全性结果与VIALE-C相似，没有新的安全性信号，并且在标准医疗护理下得到了良好的管理。在临床实践中,预计会有更多患有严重背景疾病的患者，与VIALE-C相比，这表明谨慎管理和预防不良事件非常重要。
方法：以前，根据VIALE-C标准纳入不符合强化化疗条件的未经治疗的急性髓系白血病患者.患者接受维奈托克（600毫克，第1-28天，第1周期中的4天增加），28天周期和低剂量阿糖胞苷（20mg/m2，第1-10天）。所有患者均服用肿瘤溶解综合征预防剂和水合剂。评估安全性终点。
结果：本研究纳入了14例患者。中位年龄为77.5岁（范围=61-84），78.6%超过75岁。最常见的≥3级治疗引起的不良事件是中性粒细胞减少症（57.1％）。发热性中性粒细胞减少是最常见的严重不良事件（21.4%）。一名患者出现了治疗相关的急性肾损伤，导致停止治疗。两名患者因心力衰竭和疾病进展而死亡，被认为与研究治疗无关。无患者出现肿瘤溶解综合征。
结论：安全性结果与VIALE-C相似，没有新的安全性信号，并且在标准医疗护理下得到了良好的管理。在临床实践中,预计会有更多患有严重背景疾病的患者，与VIALE-C相比，这表明谨慎管理和预防不良事件非常重要。
