背景:维奈托克(Ven)联合强化化疗被证明可有效治疗急性髓系白血病(AML)。然而,严重和长期的骨髓抑制仍然是一个令人担忧的问题。为了探索更合适的联合治疗方案,我们设计了Ven联合柔红霉素和阿糖胞苷(DA26)方案作为诱导治疗,旨在评估成人从头AML的有效性和安全性。
方法:在10家中国医院进行了2期临床试验,以研究Ven联合柔红霉素和阿糖胞苷(DA26)治疗AML患者。主要终点是总反应率(ORR),包括完全缓解(CR),完全缓解,血细胞计数恢复不完全(CRi),和部分反应(PR)。次要终点包括通过流式细胞术评估的可测量的骨髓残留病(MRD),总生存期(OS),无事件生存(EFS),无病生存率(DFS),和方案的安全性。这项研究是一项目前正在进行的试验,在中国临床试验注册中心列为ChiCTR2200061524。
结果:总体而言,2022年1月至2022年11月共纳入42例患者;54.8%(23/42)为男性,中位年龄为40岁(范围,16-60)年。一个诱导周期后的ORR为92.9%(95%置信区间[CI],91.6-94.1;39/42),复合完全缓解率(CRCRi)90.5%(95%CI,89.3-91.6,CR37/42,CRi1/42)。此外,87.9%(29/33)的CR患者MRD未检出(95%CI,84.9-90.8)。3级或更严重的不良反应包括中性粒细胞减少症(100%),血小板减少症(100%),发热性中性粒细胞减少症(90.5%),一个死亡。中性粒细胞和血小板恢复时间中位数为13(5-26)天和12(8-26)天,分别。直到2023年1月30日,估计12个月的操作系统,EFS,DFS率为83.1%(95%CI,78.8-87.4),82.7%(95%CI,79.4-86.1),和92.0%(95%CI,89.8-94.3),分别。
结论:Ven与DA(2+6)联合治疗成人初诊AML是一种非常有效和安全的诱导疗法。据我们所知,这种诱导治疗具有最短的骨髓抑制期,但与以前的研究具有相似的疗效.
BACKGROUND: Venetoclax (Ven) combined with intensive chemotherapy was proven effective in the management of acute myeloid leukemia (AML). However, the severe and prolonged myelosuppression remains a concern to worry about. To explore more appropriate combination regimens, we designed Ven combining daunorubicin and cytarabine (DA 2 + 6) regimen as induction therapy, aimed to evaluate the effectiveness and safety in adults de novo AML.
METHODS: A phase 2 clinical trial was performed in 10 Chinese hospitals to investigate Ven combined with daunorubicin and cytarabine (DA 2 + 6) in patients with AML. The primary endpoints were overall response rate (ORR), comprising of complete remission (CR), complete remission with incomplete blood cell count recovery (CRi), and partial response (PR). Secondary endpoints included measurable residual disease (MRD) of bone marrow assessed by flow cytometry, overall survival (OS), event-free survival (EFS), disease-free survival (DFS), and the safety of regimens. This study is a currently ongoing trial listed on the Chinese Clinical Trial Registry as ChiCTR2200061524.
RESULTS: Overall, 42 patients were enrolled from January 2022 to November 2022; 54.8% (23/42) were male, and the median age was 40 (range, 16-60) years. The ORR after one cycle of induction was 92.9% (95% confidence interval [CI], 91.6-94.1; 39/42) with a composite complete response rate (CR + CRi) 90.5% (95% CI, 89.3-91.6, CR 37/42, CRi 1/42). Moreover, 87.9% (29/33) of the CR patients with undetectable MRD (95% CI, 84.9-90.8). Grade 3 or worse adverse effects included neutropenia (100%), thrombocytopenia (100%), febrile neutropenia (90.5%), and one mortality. The median neutrophil and platelet recovery times were 13 (5-26) and 12 (8-26) days, respectively. Until Jan 30, 2023, the estimated 12-month OS, EFS, and DFS rates were 83.1% (95% CI, 78.8-87.4), 82.7% (95% CI, 79.4-86.1), and 92.0% (95% CI, 89.8-94.3), respectively.
CONCLUSIONS: Ven with DA (2 + 6) is a highly effective and safe induction therapy for adults with newly diagnosed AML. To the best of our knowledge, this induction therapy has the shortest myelosuppressive period but has similar efficacy to previous studies.