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.