University of North Carolina, Lineberger Comprehensive Cancer Center

This segment concludes by acknowledging ongoing research efforts aimed at refining venetoclax use, such as optimizing duration, identifying predictive biomarkers, and integrating the drug with targeted therapies, to further improve outcomes while minimizing toxicity.

Venetoclax-Based Therapy in AML: Benefits, Toxicity, and Real-World Adjustments

Segment 2 focuses on the practical use of venetoclax-based regimens in frontline AML treatment, emphasizing both their transformative clinical impact and the real-world challenges they introduce. The discussion begins with reflections on how venetoclax combined with hypomethylating agents (HMAs) has dramatically improved remission rates in older or unfit patients, enabling many to achieve deeper responses than historically possible with low-intensity therapy. Panelists describe how this success has reshaped expectations, driving ongoing exploration of venetoclax combinations in broader patient populations.

A major part of the segment centers on toxicity management, particularly prolonged cytopenias, which remain a significant barrier to treatment continuity. The experts highlight strategies such as shortening venetoclax exposure to 14 or 7 days per cycle, holding therapy between cycles, or individualizing HMA schedules. They note that although clinical trials standardized certain dosing parameters, real-world practice often requires more flexibility to avoid cumulative marrow suppression. Attention is also given to the importance of repeat bone marrow assessments early in therapy to confirm remission and guide cycle timing, especially because venetoclax-induced cytopenias may reflect therapeutic effect rather than persistent disease.

The panel discusses how patient fitness, comorbidities, and concurrent medications influence regimen selection and dose adjustments. They also point out logistical challenges, such as the need for close monitoring, transfusion support, and balancing outpatient management with safety. Despite these complexities, the consensus is that venetoclax has fundamentally changed AML care, particularly for older adults who previously had very limited treatment options.

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Throughout this segment, the panel frames the broader conversation: AML therapy is becoming more nuanced and personalized, but clinicians must navigate increasingly complex decision-making. 

Evolving Landscape of AML Therapy

This segment outlines the thematic focus on advancements in AML therapeutics. The discussion centers on how rapidly the treatment landscape has transformed over the past several years, driven largely by targeted therapies, combination regimens, and improved genomic understanding. Panelists reflect on how molecular diagnostics have become essential for guiding initial treatment decisions, shifting AML away from a one-size-fits-all model toward a far more individualized approach. They emphasize that even frontline treatment strategies now hinge on early mutational profiling, cytogenetics, and disease biology, which help distinguish patients who benefit from intensive chemotherapy versus those who achieve equal or better outcomes with lower-intensity regimens.

The discussion highlights the significant impact of venetoclax-based therapy in older and unfit patients, noting its widespread adoption and the dramatic increase in response rates observed since its introduction. At the same time, they acknowledge ongoing challenges, particularly around managing prolonged cytopenias, tailoring cycle lengths, and determining how to integrate venetoclax with emerging targeted agents. The panel also identifies major unmet needs, including improving outcomes for 

-mutated AML and other high-risk subsets. Early enthusiasm surrounding menin inhibitors is introduced as an example of how new drug classes are generating optimism for historically difficult-to-treat molecular groups, such as 

Martha L. Arellano, MD, associate professor, interim associate director, Department of Hematology and Medical Oncology, and director, Hematology and Medical Oncology Fellowship Program, Emory University School of Medicine, Winship Cancer Institute, discusses the management of older patients with acute myeloid leukemia (AML).

Age alone should not limit a patient’s treatment options, says Arellano.

In the past, older patients were restricted to either 7+3 chemotherapy or hospice care. Subsequently, hypomethylating agents became an additional option for patients, says Arellano.

Currently, venetoclax (Venclexta) is approved for use in combination with azacitidine or decitabine or low-dose cytarabine for the treatment of adult patients with newly diagnosed AML who are aged 75 years or older, or who have comorbidities that prevent the use of intensive induction chemotherapy. Although these combinations are considered breakthrough therapies, they are not curative, concludes Arellano.

Martha L. Arellano, MD, discusses the management of older patients with acute myeloid leukemia.

Martha L. Arellano, MD

Articles

Venetoclax-Based Therapy in AML: Benefits, Toxicity, and Real-World Adjustments

Evolving Landscape of AML Therapy

Dr. Arellano on Managing Older Patients With AML