Weng Guangyang, Zhang Yu, Yu Guopan, Luo Tingyue, Yu Sijian, Xu Na, Sun Zhiqiang, Lin Dongjun, Deng Lan, Liang Xinquan, Xiao Jie, Zhang Hongyu, Guo Ziwen, Shao Ruoyang, Du Xin, Jin Hua, Liu Qifa
Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Hematology, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China.
J Intern Med. 2023 Mar;293(3):329-339. doi: 10.1111/joim.13581. Epub 2022 Nov 3.
The heterogeneity of relapsed or refractory (R/R) acute myeloid leukemia (AML) leads to no response to venetoclax (VEN)-based therapy in more than half of the patients. Genetic characteristics are considered important predictors for response to treatment in adults with AML. However, the association of genetic characteristics with outcomes receiving VEN-based therapy is incompletely understood in R/R AML.
To evaluate the efficacy of VEN combined with hypomethylating agents (HMA) and identify the potential genetic predictors of response in R/R AML.
A total of 150 R/R AML patients treated with VEN combined with HMA were enrolled in this retrospective study. Outcomes of the response and overall survival (OS) were analyzed. The predictors of response and OS were analyzed by logistic regression or Cox proportional hazards model.
With a median of two (range, 1-4) cycles of therapy, the overall response rate was 56.2%, including 22.0% complete remission (CR), 21.3% CR with incomplete hematologic recovery, 2.0% morphologic leukemia-free state, and 10.7% partial remission, in which 25 patients achieved measurable residual disease (MRD)-negative response. With a median follow-up of 11.2 [95% confidence interval (CI), 7.2-14.8] months, 1- and 2-year OS were 46.9% (95% CI, 37.8%-58.1%) and 38.9% (95% CI, 28.7%-52.9%), respectively. Adverse cytogenetics and European Leukemia Net (ELN) risk predicted inferior response to VEN-based therapy. Mutations in IDH1/2, NPM1, ASXL1, and chromatin-cohesin genes predicted superior response to VEN-based therapy, whereas mutations in active signaling genes such as FLT3-ITD and K/NRAS predicted inferior response.
VEN combined with HMA was effective with R/R AML patients, and the response to treatment was associated with genetic characteristics.
复发或难治性（R/R）急性髓系白血病（AML）的异质性导致超过半数患者对基于维奈克拉（VEN）的治疗无反应。遗传特征被认为是成人AML治疗反应的重要预测指标。然而，在R/R AML中，遗传特征与接受基于VEN治疗的结局之间的关联尚未完全明确。
评估VEN联合低甲基化药物（HMA）的疗效，并确定R/R AML中反应的潜在遗传预测指标。
本回顾性研究共纳入150例接受VEN联合HMA治疗的R/R AML患者。分析反应和总生存（OS）结局。通过逻辑回归或Cox比例风险模型分析反应和OS的预测指标。
中位治疗2（范围1-4）个周期，总反应率为56.2%，包括22.0%完全缓解（CR）、21.3%伴有血液学不完全恢复的CR、2.0%形态学无白血病状态和10.7%部分缓解，其中25例患者达到微小残留病（MRD）阴性反应。中位随访11.2[95%置信区间（CI），7.2-14.8]个月，1年和2年OS分别为46.9%（95%CI，37.8%-58.1%）和38.9%（95%CI，28.7%-52.9%）。不良细胞遗传学和欧洲白血病网络（ELN）风险预测对基于VEN治疗的反应较差。异柠檬酸脱氢酶1/2（IDH1/2）、核仁磷酸蛋白1（NPM1）、附加体结合型X连锁白血病相关蛋白1（ASXL1）和染色质黏连蛋白基因突变预测对基于VEN治疗的反应较好，而诸如FMS样酪氨酸激酶3内部串联重复（FLT3-ITD）和K/NRAS等激活信号基因突变预测反应较差。
VEN联合HMA对R/R AML患者有效，且治疗反应与遗传特征相关。
