维奈克拉联合阿扎胞苷治疗急性髓系白血病的近期疗效：单中心数据

OBJECTIVE: To explore the safety and short-term efficacy of venetoclax combined with azacitidine (Ven+AZA) in previously untreated patients unfit for standard chemotherapy and patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) in China. METHODS: A retrospective study was conducted in 60 previously untreated patients unfit for standard chemotherapy and patients with R/R AML who received Ven + AZA (venetoclax, 100 mg D1, 200 mg D2, 400 mg D3–28; azacitidine, 75 mg/m(2) D1–7) at the Peking University Institute of Hematology from June 1, 2019 to May 31, 2021. The incidence of adverse events, complete remission (CR)/CR with incomplete hematological recovery (CRi) rate, objective remission rate (ORR), and minimal residual disease (MRD) status in patients with different risk stratification and gene subtypes were analyzed. RESULTS: The median age of the patients was 54 (18–77) years, 33 (55.0％) were males, and the median follow-up time was 4.8 (1.4–26.3) months. Among the 60 patients, 24 (40.0％) were previously untreated patients unfit for standard chemotherapy, and 36 (60.0％) were R/R patients. The median mumber cycles of Ven+AZA in the two groups were both 1 (1–5). According to the prognostic risk stratification of the National Comprehensive Cancer Network, it was divided into 8 cases of favorable-risk, 2 cases of intermediate risk, and 14 cases of poor-risk. In previously untreated patients unfit for standard chemotherapy, after the first cycle of Ven+AZA, 17/24 (70.8％) cases achieved CR/CRi, 3/24 (12.5％) achieved partial remission (PR), and the ORR was 83.3％. Among them, nine patients received a second cycle chemotherapy and two received a third cycle. Among CR/CRi patients, 8/17 (47.1％) achieved MRD negativity after two cycles of therapy. In the R/R group, after the first cycle of Ven+AZA, 21/36 (58.3％) cases achieved CR/CRi (7/21 achieved MRD negativity), 3 achieved PR, and the ORR was 66.7％. Among R/R patients, 12 were treated for more than two cycles. There were no new CR/CRi patients after the second treatment cycle, and 14 cases (66.7％) achieved MRD negativity. According to the time from CR to hematological recurrence, the R/R group was divided into 12 cases in the favorable-risk group (CR to hematological recurrence ≥18 months) and 24 in the poor-risk group (CR to hematological recurrence <18 months, no remission after one cycle of therapy, and no remission after two or more cycles of therapy). Eleven of 24 (45.8％) cases achieved CR/CRi after one cycle of Ven+AZA in the poor-risk R/R group, and 10 of 12 (83.3％) achieved CR/CRi in the favorable-risk R/R group, which was significantly superior to the poor-risk group (P＝0.031). After one cycle of treatment, 13 patients with IDH1/2 mutations and 4 that were TP53-positive all achieved CR/CRi. The CR/CRi rate of 18 patients with NPM1 mutations was 77.8％. Five patients with RUNX1-RUNX1T1 combined with KIT D816 mutation (two initial diagnoses and three recurrences) had no remission. Ven+AZA was tolerable for AML patients. CONCLUSION: Ven+AZA has acceptable safety in previously untreated patients unfit for standard chemotherapy, patients with R/R AML can achieve a high response rate, and some patients can achieve MRD negativity. It is also effective in NPM1-, IDH1/IDH2-, and TP53-positive patients. The long-term efficacy remains to be observed.