Objective: To explore the efficacy and survival of venetoclax based (VEN-based) regimen in the treatment of acute myeloid leukemia（AML）.
Methods: A retrospective study was conducted in patients who received VEN-based regimen and completed at least 1 course of efficacy evaluation at the The First Affiliated Hospital of Nanchang University from July 2019 to July 2022. The incidence of complete remission （CR）/CR with incomplete hematologic recovery （CRi） rate, objective remission rate（ORR） and survival of patients with different risk strati- fication and gene subtypes were analyzed.
Results: A total of 79 patients were enrolled, including 43 patients with newly diagnosed unfit AML （unfit AML） and 36 relapsed/refractory AML (R/R AML). The median age of the patients was 62(14-83) years old. 36 out of 79 patients achieved CR/CRi and the ORR of the whole cohort was 64.6%. The CR/CRi rate of unfit AML patients was significantly higher than that of R/R AML patients (60.5% vs 27.8%, P=0.004). In unfit AML cohort, the patients with NPM1 and IDH1/2 mutations were benefited, 8 out of 9 patients ahcieved CR/CRi, 7/8 and 5/8 patients achieved minimal residual disease (MRD) negativity, respectively. Six out of 9 patients with TET2 mutation achieved CR/CRi, 3/6 patients achieved MRD negativity. In R/R AML cohort, 2 out of 3 patients with RUNX1 mutation achieved CR/CRi, without MRD negative, while the CR/CRi rate of patients with other gene mutations was lower than 40%. The median follow-up time was 10.1(95%CI: 8.6-11.6) months. In whole cohort, the median overall survival (mOS) time was 9.1 months and the relapse free survival (RFS) time was not reached. The mOS and RFS of unfit AML patients were significantly longer than those of R/R AML patients (14.1 vs 6.8 months, P=0.013; not reached vs 3.3 months, P=0.000). In unfit AML cohort, the mOS of patients with NPM1 or IDH1/2 mutations was not reached, while that of patients without NPM1 or IDH1/2 mutations was 8.0 months (P=0.009; P=0.022). Furthermore, the mOS of patients with TP53 mutaion was significantly shorter than that of patients without TP53 mutation (5.2 vs 14.1 months， P=0.049). In R/R AML cohort, there was no significant difference in mOS between patients with mutation in each gene subtype and those without gene mutation (P>0.05). All patients had hematology adverse reactions, 91.1% patients had AE grade≥3. The most common non-hematology adverse reactions was infection, with an incidence of 91.1%. VEN-based regimen was tolerable for AML patients.
Conclusion: VEN-based regimen can achieve a high response rate, especially in unfit AML with acceptable safety, and some patients can achieve MRD negative. It is also effective in NPM1-, IDH1/2-positive patients with long survival time.
题目: 维奈克拉为基础的方案治疗急性髓系白血病疗效及生存分析.
目的: 探讨维奈克拉为基础（VEN-based）的方案治疗急性髓系白血病（AML）（非M3型）的疗效及生存情况.
方法: 回顾性分析2019年7月至2022年7月在南昌大学第一附属医院接受VEN-based方案治疗且至少完成1个疗程疗效评估的AML患者，分析患者的完全缓解（CR）/完全缓解伴血细胞计数未完全恢复（CRi）率、客观缓解率（ORR）及生存情况.
结果: 本研究共纳入79例患者，包括43例初治不适合强化疗（unfit）AML患者，36例复发难治（R/R）AML患者，中位年龄62（14-83）岁。总队列获得CR/CRi患者36例，ORR为64.6%。Unfit AML患者CR/CRi率明显高于R/R AML患者（60.5% vs 27.8%，P=0.004）。Unfit AML各基因亚型患者均可从中获益，其中NPM1及IDH1/2突变患者获益最大，均有8例患者获得CR/CRi（8/9），微小残留病（MRD）转阴患者分别为7例（7/8）和5例（5/8）；其次为TET2突变患者，6例获得CR/CRi（6/9），MRD转阴率为50%。R/R AML队列中，3例伴RUNX1突变患者中2例获得CR/CRi，MRD均未转阴，伴其他基因突变患者CR/CRi率均低于40%。中位随访时间为10.1（95%CI： 8.6-11.6）个月，中位总生存（mOS）时间为9.1个月，无复发生存时间（RFS）未达到。Unfit AML患者mOS及RFS均明显长于R/R AML患者（14.1 vs 6.8个月，P=0.013；未达到 vs 3.3个月, P=0.000）。Unfit AML患者中伴NPM1和IDH1/2突变者mOS均未达到，无NPM1和IDH1/2突变患者mOS均为8个月（P=0.009; P=0.022）；伴TP53突变者mOS明显短于无突变患者（5.2 vs 14.1个月，P=0.049）。R/R AML患者中各基因亚型突变与未突变患者间mOS均无显著差异（P>0.05）。所有患者均发生血液学不良反应，91.1%患者血液学AE分级≥3级；非血液学不良反应最常见为感染，发生率为91.1%，VEN-based方案总体耐受性好.
结论: VEN-based的方案尤其在初治unfit患者中，可以获得高应答率，且安全性可接受。该方案在伴NPM1、IDH1/2基因突变的unfit AML患者中疗效显著，这部分患者可快速获得MRD转阴，且生存期延长.
Keywords: acute myeloid leukemia; efficacy; survival; venetoclax.