Efficacy and Safety of Venetoclax Combine Azacitidine for Acute Myeloid Leukemia in China: A Real-World Single-Center Study
Authors: Bai Jiefei , Liu Hui , Li Jiangtao , Wang Ting , Zhang Chunli , Yang Yazi , Yun Xiaoya , Yin Jingjing , Qian Long , Zhao Fei , Feng Ru , Jing Hongmei 
Published: December 2024

Background: Venetoclax (VEN) and azacitidine (AZA) are used to treat patients with newly diagnosed acute myeloid leukemia (AML) who are unfit for intensive chemotherapy or relapse/refractory AML, it is important to understand the real-world usage patterns and the outcomes after VEN-AZA therapy failure, which is crucial as it remains poorly studied.
Methods: A single-center retrospective cohort study was conducted on 50 AML patients (29 newly diagnosed, 21 relapse or refractory) treated with VEN-AZA at Beijing Hospital from January 2020 to November 2023.The study was approved by the ethics committee of Beijing Hospital and adhered to the Declaration of Helsinki. The primary endpoint was overall survival, and the secondary endpoints included composite complete remission, partial remission, overall response rate, event free survival, minimal residual disease (MRD) rate, adverse event (AE) rate and the outcomes after VEN-AZA therapy failure.
Results: Among newly diagnosed AML patients, the median age was 74 years. The median follow-up was 10.1 months, and the median EFS and OS were 9.87 months and 11.93 months. The ORR, CR/CRi, and MRD (&lt;0.1%) negativity rates were 85.7%, 67.9%, and 26.3%, respectively. Twelve patients (1 refractory, 11 relapsed) received subsequent treatment following first-line VEN-AZA therapy failure. One refractory patient received VEN-AZA plus Selinexor, achieving partial remission. Two relapsed patients received VEN-AZA plus Chidamide or Gilteritinib, with one achieving CRi. One patient discontinued VEN-AZA independently for five months and relapsed, then reinitiated VEN-AZA, achieving CR after 2 cycles. The median OS after first-line VEN-AZA failure was 1.6 months (range 0-8.27 months).
For relapsed/refractory AML patients, the median age was 65 years. The median follow-up was 8.53 months, and the median EFS and OS were 5.2 months and 9.1 months. The ORR, CR/CRi, and MRD (&lt;0.1%) negativity rates were 52.4%, 42.9%, and 11.11%, respectively. Ten patients (2 refractory, 8 relapsed) received subsequent treatment. Two refractory patients received chemotherapy (CAG/HA), with one achieving CRi. Among the eight relapsed patients, two received VEN-AZA plus Enasidenib or Gilteritinib, both achieving CRi. Two patients participated in clinical trials (CAR-NK and CD33-ADC therapy) with an ORR of 50%. The median OS after second-line or more VEN-AZA failure was 0.67 months (range 0-8.63 months). Patients with six or more therapy cycles and achieving CR/CRi had longer EFS and OS. The main adverse events were hematological and infections.
Conclusions: The VEN-AZA combination offers high efficacy and manageable toxicities in real-world settings. Patients with AML following failure of frontline VEN-AZA therapy often choose VEN-AZA plus targeted therapy, which offers the best efficacy. Following failure of second-line or beyond VEN-AZA therapy, patients typically choose induction chemotherapy, VEN-AZA plus targeted therapy, or clinical trials.
KEYWORDS
acute myeloid leukemia, hypomethylating agents, Venetoclax, relapse, refractory