Impact of AML1/ETO Fusion on the Efficacy of Venetoclax Plus Hypomethylating Agents in Newly Diagnosed Acute Myeloid Leukemia

IF 4.4 3区医学 Q2 ONCOLOGY Targeted Oncology Pub Date : 2024-03-11 DOI:10.1007/s11523-024-01039-y

Dian Jin, Haoguang Chen, Jingsong He, Yi Li, Gaofeng Zheng, Yang Yang, Yi Zhao, Jing Le, Wenxiu Shu, Donghua He, Zhen Cai

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Abstract

Background

AML1/ETO fusion confers favorable prognosis in acute myeloid leukemia (AML) treated with intensive chemotherapy (IC). However, the impact of AML1/ETO fusion on the efficacy of venetoclax in the treatment of AML is unclear.

Objective

The aim of this study was to evaluate the efficacy of venetoclax plus hypomethylating agents (VEN/HMAs) in patients with AML1/ETO-positive AML.

Patients and Methods

Patients with newly diagnosed AML in two centers were reviewed and divided into three cohorts: AML1/ETO-positive AML treated with frontline VEN/HMA (Cohort A), AML1/ETO-negative AML treated with frontline VEN/HMA (Cohort B), or AML1/ETO-positive AML treated with frontline IC (Cohort C). The response and survival were compared between the cohorts.

Results

A total of 260 patients were included in the study. Patients in Cohort A had a significantly lower overall response rate (ORR) than patients in Cohort B (40.9% vs 71.2%, p = 0.005). The median event-free survival (EFS) in Cohort A and Cohort B was 2.7 months and 7.7 months, respectively, with no significant difference. The ORR and median EFS in Cohort C were 80.8% and 14.9 months, respectively, which were significantly superior to those in Cohort A, and the advantages remained significant after propensity score matching. ORR and EFS in KIT-mutated patients with AML1/ETO-positive AML receiving VEN/HMA were much inferior to those in KIT wild-type patients (ORR 0.0% vs 81.8%, p = 0.001; EFS 1.2 months vs not reached, p < 0.001).

Conclusions

Newly diagnosed AML patients with AML1/ETO fusion had a poor response to frontline VEN/HMA treatment. When determining induction therapy for patients with AML1/ETO-positive AML, IC should be preferred over VEN/HM.

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AML1/ETO融合对新诊断的急性髓性白血病患者服用Venetoclax和低甲基化药物疗效的影响

背景AML1/ETO融合使接受强化化疗（IC）的急性髓性白血病（AML）患者预后良好。然而，AML1/ETO融合对venetoclax治疗急性髓细胞白血病疗效的影响尚不清楚。本研究旨在评估venetoclax加低甲基化药物（VEN/HMAs）在AML1/ETO阳性急性髓细胞白血病患者中的疗效：AML1/ETO阳性AML患者接受一线VEN/HMA治疗（队列A），AML1/ETO阴性AML患者接受一线VEN/HMA治疗（队列B），或AML1/ETO阳性AML患者接受一线IC治疗（队列C）。研究共纳入了 260 例患者。A组患者的总反应率（ORR）明显低于B组患者（40.9% vs 71.2%，P = 0.005）。A 组和 B 组患者的中位无事件生存期（EFS）分别为 2.7 个月和 7.7 个月，无明显差异。队列C的ORR和中位无事件生存期分别为80.8%和14.9个月，明显优于队列A，倾向得分匹配后优势依然显著。KIT突变的AML1/ETO阳性AML患者接受VEN/HMA治疗的ORR和EFS远逊于KIT野生型患者（ORR为0.0% vs 81.8%，p = 0.001；EFS为1.2个月 vs 未达到，p <0.001）。在决定对AML1/ETO阳性的急性髓细胞性白血病患者进行诱导治疗时，IC应优于VEN/HM。

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来源期刊

Targeted Oncology 医学-肿瘤学

CiteScore

8.40

自引率

3.70%

发文量

审稿时长

>12 weeks

期刊介绍： Targeted Oncology addresses physicians and scientists committed to oncology and cancer research by providing a programme of articles on molecularly targeted pharmacotherapy in oncology. The journal includes: Original Research Articles on all aspects of molecularly targeted agents for the treatment of cancer, including immune checkpoint inhibitors and related approaches. Comprehensive narrative Review Articles and shorter Leading Articles discussing relevant clinically established as well as emerging agents and pathways. Current Opinion articles that place interesting areas in perspective. Therapy in Practice articles that provide a guide to the optimum management of a condition and highlight practical, clinically relevant considerations and recommendations. Systematic Reviews that use explicit, systematic methods as outlined by the PRISMA statement. Adis Drug Reviews of the properties and place in therapy of both newer and established targeted drugs in oncology.