In a landmark real-world study emerging from China, researchers have provided compelling evidence on the efficacy and safety of combining venetoclax with azacitidine for the treatment of acute myeloid leukemia (AML). This breakthrough sheds light on therapeutic outcomes in both newly diagnosed and relapsed or refractory AML patients, offering critical insights into treatment patterns outside of clinical trials. As AML remains a notoriously aggressive and heterogeneous hematological malignancy, innovations in frontline and salvage therapies are vital for improving survival and quality of life.
Venetoclax (VEN), a potent BCL-2 inhibitor, has revolutionized AML treatment by inducing apoptosis in malignant cells, especially in patients deemed unfit for intensive chemotherapy. Azacitidine (AZA), a hypomethylating agent, complements VEN by modifying gene expression, thus facilitating leukemic cell death and reversing aberrant epigenetic alterations. Their combination has been approved in several countries for frontline AML therapy in older or frail patients but real-world data, particularly from Asian populations, have been limited until now.
The recently published retrospective cohort study at a single center in China included 50 adult AML patients treated between January 2020 and November 2023. The patient cohort comprised 29 individuals with newly diagnosed AML and 21 patients with relapsed or refractory disease, providing a comprehensive overview of VEN-AZA’s impact across the disease spectrum. The investigators employed rigorous endpoints such as overall survival (OS), composite complete remission (CR) inclusive of incomplete hematologic recovery (CRi), partial remission (PR), and event-free survival (EFS), alongside minimal residual disease (MRD) assessment and adverse event monitoring.
.adsslot_QvzLjF5Itp{width:728px !important;height:90px !important;}
@media(max-width:1199px){ .adsslot_QvzLjF5Itp{width:468px !important;height:60px !important;}
}
@media(max-width:767px){ .adsslot_QvzLjF5Itp{width:320px !important;height:50px !important;}
}
ADVERTISEMENT
Among the newly diagnosed cohort, the outcomes were notably encouraging. With a median age of 74 years, reflecting a population typically ineligible for high-intensity chemotherapy, patients demonstrated a median EFS of 9.87 months and an OS nearing a full year at 11.93 months. These survival metrics underscore VEN-AZA’s capacity to deliver meaningful clinical benefit in elderly AML patients, a group historically beset by poor prognosis. Impressively, the overall response rate (ORR) reached 85.7%, with two-thirds achieving CR or CRi. MRD negativity, an emerging surrogate for deep remission and long-term survival probability, was achieved in over a quarter of this subgroup.
The study did not stop at initial responses; it explored therapeutic avenues following VEN-AZA failure, a critical but understudied phase. Post-failure treatments included combination regimens of VEN-AZA with targeted agents such as gilteritinib, chidamide, or selinexor. While these combinations yielded partial remissions or CRi, the median survival after treatment failure remained limited to 1.6 months, highlighting the urgent need for more efficacious salvage strategies. The integration of novel agents appears promising but requires further validation in robust clinical trials.
Turning to the subset with relapsed or refractory AML, median age was younger at 65 years but prognosis was poorer. Median EFS was curtailed to 5.2 months and OS to 9.1 months, reflecting the aggressive nature of disease in this context and the relative resistance to salvage therapies. Here, the ORR was lower at 52.4%, and CR/CRi was attained in just under half the patients. Furthermore, only about 11% achieved MRD negativity, indicating residual disease persistence and the challenge of overcoming chemoresistance.
Post-failure strategies in relapsed or refractory AML included induction chemotherapy, VEN-AZA combined with agents like enasidenib or gilteritinib, as well as enrollment in clinical trials evaluating novel therapies. Responses were heterogeneous, with a median post-failure OS of less than a month (0.67 months), underscoring the vulnerability of this population and the imperative to enhance salvage treatment efficacy. Adverse events were predominantly hematologic and infectious complications, consistent with the known toxicity profiles of VEN and AZA, demanding vigilant supportive care.
This study’s findings reinforce VEN-AZA’s role as a pivotal frontline treatment in AML patients who cannot tolerate conventional chemotherapy, delivering high remission rates with manageable safety concerns. The data importantly emphasize that combining VEN-AZA with targeted therapies post-failure can extend survival beyond VEN-AZA alone, suggesting that precision medicine approaches tailored to molecular mutations and disease dynamics might optimize outcomes.
Moreover, the investigation highlights the real-world complexities and heterogeneity encountered outside controlled trials, such as variations in age, disease status, and prior therapies, which can influence response rates and toxicity. These insights foster a more nuanced understanding of how VEN-AZA regimens perform in everyday clinical practice, facilitating more informed therapeutic decisions.
While encouraging, the limited sample size and single-center design necessitate cautious interpretation. The authors call for larger, multicenter studies to confirm these observations and refine predictive biomarkers for response and resistance. Optimizing dosing, sequencing, and combination partners are key areas for exploration to maximize efficacy while minimizing adverse effects.
The emergence of targeted agents such as FLT3 inhibitors (e.g., gilteritinib), IDH inhibitors (e.g., enasidenib), and epigenetic modulators offer fertile ground for combinatorial regimens with VEN-AZA, potentially transforming the treatment paradigm in relapsed or refractory AML. Furthermore, MRD monitoring may guide treatment intensity and duration, identifying patients who might benefit from consolidation or allogeneic stem cell transplant.
In terms of safety, the study confirmed that hematologic toxicity and infections remain the most common adverse events but are generally manageable with contemporary supportive care measures. These findings highlight the importance of infection prophylaxis and close monitoring, particularly given the immunosuppressive effects inherent to AML and its treatment.
Overall, this real-world data enriches the evolving landscape of AML therapeutics by validating VEN-AZA’s efficacy and safety in a Chinese population, extending understanding beyond prior Western-centric clinical trials. It also underscores the limitations faced once VEN-AZA fails, underscoring a critical need for novel agents and strategic sequencing to overcome resistance and prolong survival.
The insights gained could accelerate the adoption of VEN-AZA-based regimens in diverse clinical settings globally while inspiring further research into combinatorial strategies that harness targeted therapy synergy. This progress brings hope to patients with AML, particularly older adults and those with limited treatment options, moving the field toward more personalized and effective interventions against a devastating disease.
As the fight against acute myeloid leukemia advances, integrating real-world evidence with translational research and emerging therapies is paramount. This study stands as a testament to the potential of VEN-AZA combination therapy and the imperative to innovate continuously in the quest to improve patient outcomes in AML.
Subject of Research: Efficacy and safety of venetoclax and azacitidine combination therapy in patients with acute myeloid leukemia, including outcomes post-therapy failure.
Article Title: Efficacy and safety of venetoclax and azacitidine for acute myeloid leukemia in China: a real-world single-center study.
Article References:
Bai, JF., Wang, T., Li, JT. et al. Efficacy and safety of venetoclax and azacitidine for acute myeloid leukemia in China: a real-world single-center study.
BMC Cancer 25, 990 (2025). https://doi.org/10.1186/s12885-025-14167-z
Image Credits: Scienmag.com
DOI: https://doi.org/10.1186/s12885-025-14167-z
Tags: acute myeloid leukemia treatment insightsAsian populations AML clinical dataBCL-2 inhibitors and leukemiaefficacy of venetoclax in AMLfrontline therapy for acute myeloid leukemiahypomethylating agents in cancer treatmentnovel therapies for aggressive hematological malignanciespatient outcomes in AML treatmentreal-world study AML Chinasafety of azacitidine in AMLtreating relapsed refractory AMLvenetoclax azacitidine combination therapy
