Why a Gentler AML Regimen Outperforming Chemotherapy Matters

Intensive induction chemotherapy has been the standard for fit patients with acute myeloid leukemia (AML) for more than 5 decades, requiring weeks of hospitalization and carrying significant toxicity.

Amir T. Fathi, MD, director of the Leukemia Program at the Massachusetts General Brigham Cancer Institute in Boston and a professor of medicine at Harvard Medical School, spoke with CancerNetwork^® about the significance of a lower-intensity regimen improving event-free survival (EFS) over chemotherapy in this population. He spoke in the context of findings from the phase 2 PARADIGM trial (NCT04801797) that he and colleagues published in the New England Journal of Medicine, which showed a median EFS of 14.5 months (95% CI, 10.4-24.4) with venetoclax (Venclexta) plus azacitidine (Vidaza) vs 6.2 months (95% CI, 4.1-10.1) with induction chemotherapy (HR, 0.57; 95% CI, 0.39-0.84; P = .002 by stratified log-rank test).

Transcript:

CancerNetwork: How significant is it, in your view, that a lower-intensity regimen actually improved EFS vs chemotherapy in patients who were fit enough for induction?

Fathi: Context is very important. There is a long history here [of] more than 5 decades of very intensive, often toxic, often prolonged treatment for patients with AML. There’s a reason why we reserve intensive induction, oftentimes, for fit patients; you need to be fit to tolerate treatment, stay in the hospital for 4, often 5, weeks, and be impacted by the rigor of all of it.

To be able to move, at least in a subset of patients who would traditionally receive this treatment, to a more gentle treatment that does not cause, for example, as significant marrow suppression, less mucosal toxicity, less risk of infection and bleeding, at least numerically, based on the trial, less time in the hospital, a better quality of life during the initial course of treatment, and yet have better efficacy and get to transplant at a higher rate, is a very important outcome. There are limitations, obviously, to the clinical trial; it did not enroll all AML subtypes, but it did enroll a substantial subset of [patients with] AML who would traditionally receive the more intensive chemotherapy that we’ve used for decades.

Reference

Fathi AT, Perl AE, Fell GG, et al. Azacitidine-venetoclax or induction chemotherapy for acute myeloid leukemia. N Engl J Med. 2026;395(9):845-858. doi:10.1056/NEJMoa2602804