Background Patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) have dismal outcomes, representing an urgent unmet need. Venetoclax has exhibit encouraging anti-tumor activity in AML. The clinical efficacy of the CAG regimen (cytarabine, aclarubicin, G-CSF) in patients with R/R AML has been confirmed in previous studies. The aim of this study was to explore the safety and efficacy of the venetoclax plus CAG regimen and in patients with R/R AML.

Methods A total of 51 patients with refractory/relapsed acute myeloid leukemia (AML) who received venetoclax combined with CAG treatment at Peking University People's Hospital from February 2023 to September 2024 were prospectively enrolled in this study (NCT05918198). Patients who achieve CCR typically undergo 1–2 cycles of consolidation chemotherapy prior to proceeding with hematopoietic stem cell transplantation (HSCT). To assess efficacy, we evaluated the CCR rate, minimal residual disease (MRD) elimination rate, overall response rate (ORR), disease-free survival (DFS), and overall survival (OS) following treatment with the Venetoclax plus CAG regimen. Adverse events (AEs) were assessed using the NCI CTCAE version 5.0 to evaluate both the overall incidence of AEs and the incidence of grade 3 or higher AEs, thereby providing a comprehensive safety profile for the venetoclax combined with CAG regimen in relapsed/refractory AML patients.

Results Among the 51 patients who accepted data analysis, there were 19 relapse patients (37.3%) and 32 refractory patients (62.7%).The proportions of patients in the favorable, intermediate and poor groups were 24 cases (47.1%), 12 cases (23.5%) and 15 cases (24.9%), respectively.The median follow-up time was 391.5 (36 - 606) days.

After one cycle of venetoclax plus CAG regimen treatment, 43 patients achieved CCR. Among the 50 patients evaluated for efficacy after treatment, the CCR rate was 86.0%. One patient (1.9%) achieved a partial response (PR) and six patients were non-responders (NR) (12%). The ORR was 88%. Among the 43 patients who achieved CCR, nine patients (17.3%) had negative MRD, and the MRD elimination rate among patients who achieved CCR was 20.9%. Of the 19 patients in the relapse group, all achieved CCR, with a CCR rate of 100%. Among them, 6 patients had MRD negativity, and the MRD clearance rate was 31.6%. In the refractory group of 32 patients, 24 patients achieved CCR, with a CCR rate of 75%. Among them, 3 patients had MRD negativity, and the MRD clearance rate was 12.5%. The CCR rate of the relapse group was significantly higher than that of the refractory group (P=0.018).

Among the patients who achieved CCR, the 1-year cumulative relapse rate was 23.8%. The 1-year DFS is 68.6%. The1-year DFS of favorable, intermediate, and poor risk groups were 77.1%, 65.6%, and 54.0%, respectively. The 1-year OS is 76.2%. The1-year OS of favorable, intermediate, and poor risk groups were 85.1%, 56.3%, and 78.6%, respectively. The1-year OS of relapsed and refractory groups were 81.5%and 72.1%, respectively. Of the 43 patients who achieved CCR, 16 (37.2%) underwent HSCT after achieving remission. Of the 6 patients with NR, 2 (33.3%) patients received HSCT. Notably, all patients who underwent HSCT remained alive during the follow-up period, the median survival time after HSCT was 424 (105 - 540) days.

For all enrolled patients, the overall incidence of grade 3 or higher hematological AEs was 88.2%, with 74.5% attributed to treatment-related causes. Specifically, febrile neutropenia occurred in 41.2% of patients. For grade 3-4 leukopenia, the total incidence was 86.3%, including 35.3% observed prior to treatment and 51.0% induced by treatment. The incidence of grade 3 and above non-hematological AEs was 25.5%. The most common non-hematological AE was infection (23.5%).

Conclusion The venetoclax plus CAG regimen can serve as a safe and effective new option for salvage chemotherapy in patients with R/R AML. This combined regimen may help more patients to achieve the opportunity to recieve HSCT with a smaller tumor budern and improve the outcomes of patients.

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2025
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