Intensive Chemotherapy Versus Venetoclax-Based Regimens in Elderly Patients with Acute Myeloid Leukemia: Is the Chemotherapy Era Ending?

Background: Acute myeloid leukemia (AML) primarily affects older adults and is associated with poor prognosis, particularly in patients aged ≥ 60 years with comorbidities and adverse disease characteristics. Standard intensive chemotherapy, such as the "7 + 3" regimen, has shown limited efficacy and substantial toxicity in this population, underscoring the need for alternative treatment strategies. In recent years, venetoclax-based regimens have emerged as an important option, demonstrating promising outcomes in elderly patients traditionally considered unfit for intensive therapy and, more recently, even in selected fit patients. Methods: This narrative review provides a comprehensive comparative analysis of intensive chemotherapy and venetoclax-based regimens in elderly AML patients. This review synthesizes evidence from prospective and retrospective clinical trials, with focuses on treatment efficacy, safety, and the ability to bridge patients to curative allogeneic hematopoietic stem cell transplantation (allo-HSCT). Results: Intensive chemotherapy has achieved complete remission (CR) rates of 40-60% in elderly AML patients, though the median overall survival (OS) rarely exceeds 12 months. Conversely, venetoclax combined with hypomethylating agents has recently demonstrated CR rates of up to 74%, with 83% of responders proceeding to allo-HSCT in selected studies. Venetoclax-based regimens have also been associated with improved tolerability and reduced treatment-related mortality. Discussion: This review highlights a paradigm shift in the management of AML in the elderly. While intensive chemotherapy remains a standard option for selected patients, the increasing use of venetoclax-based regimens represents a novel and effective strategy with the potential to overcome traditional limitations, especially in patients previously deemed ineligible for curative approaches. The high remission and transplantation rates observed with non-intensive therapies support their role not only as a palliative alternative but as a bridge to cure. Conclusions: Venetoclax-based regimens are reshaping the treatment landscape of AML in the elderly, offering high response rates and facilitating access to allo-HSCT. Further research is needed to optimize treatment sequencing, explore novel combinations, and reduce relapse rates after transplants, ultimately improving the long-term outcomes in this high-risk population.