Transplant Eligibility, Post-Induction Decisions, and Real-World Complexity

Segment 4 examines how clinicians navigate transplant eligibility and early treatment choices in AML, particularly during the first days of diagnosis when critical decisions must be made without complete molecular information. The panel discusses the frequent dilemma: patients often require treatment initiation before next-generation sequencing or donor identification is available. This uncertainty complicates the decision between intensive induction and lower-intensity regimens. They emphasize the need for rapid turnaround testing, though many centers still wait weeks to receive full molecular data, making early treatment choices dependent on clinical stability and disease urgency rather than precise risk stratification.

The speakers debate whether prioritizing less intensive approaches risks sacrificing long-term outcomes for some patients—particularly younger, potentially transplant-eligible individuals with biologically aggressive disease. They note that although venetoclax-based regimens have shown strong remission rates and tolerability, the long-term survival after allogeneic transplant may differ from outcomes achieved following more intensive induction, especially in select molecular subsets.

A central focus is the recently discussed retrospective Hopkins analysis comparing post-transplant outcomes between patients receiving venetoclax-based therapy versus intensive chemotherapy. Although the data looked encouraging for venetoclax as a transplant bridge, the panel acknowledges its limitations, including lack of randomization and potential selection biases. They contrast this with other emerging data, such as results from CPX-351 and broader CP regimens, showing impressive long-term transplant survival in certain AML/myelodysplastic syndrome (MDS)-related cases, raising questions about whether less intensive approaches can fully replicate these outcomes.

Despite the uncertainties, the clinicians note that in real practice, they must choose a regimen for the patient in front of them. Considering available evidence, many would still favor venetoclax-based therapy for stable, transplant-eligible patients with AML when mutation profiles suggest potential benefit, especially those with secondary-type mutations. This segment highlights the tension between evolving low-intensity strategies and the enduring need to ensure optimal transplant-related long-term survival.