How Does Azacitidine/Venetoclax Impact Hospital Burden in AML?

In the phase 2 PARADIGM trial (NCT04801797), no patients who received azacitidine (Vidaza) plus venetoclax (Venclexta) were admitted to the intensive care unit or died within 30 or 60 days, compared with a 10% ICU admission rate and 3% and 5% mortality rates, respectively, among those who received induction chemotherapy for acute myeloid leukemia (AML). The mean number of inpatient days in the first 30 days with the combination was roughly half of that seen with chemotherapy.

Lead study author 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 how much weight this toxicity and hospitalization difference should carry in treatment decisions.

Transcript:

CancerNetwork: With venetoclax/azacitidine, there were no ICU admissions, roughly half the mean of inpatient days vs chemotherapy, and no 30- or 60-day mortality. How much weight should that toxicity and hospital burden difference carry in a treatment decision, independent of the efficacy numbers?

Fathi: Keeping in mind that the primary end point of the study was the assessment of efficacy by event-free survival, and understanding that safety, tolerability, and adverse events were secondary end points, the majority of leukemia physicians realize that the combination of a hypomethylating agent [HMA] plus venetoclax, such as azacitidine plus venetoclax, is better tolerated. The fact that, among at least the 86 patients we studied here, none of them died within that first initial period of treatment, whereas some did in the intensive chemotherapy arm; that 10% went to the ICU in the intensive chemotherapy arm, but none did so in the HMA-venetoclax arm, in that population of patients, in my view, is supportive of what we oftentimes see in our clinic. It probably, in my view, should not be surprising; if you’re giving this drug combination to patients 75 and up, where it is currently approved, it should not be surprising that if you give it to younger, more fit patients, the likelihood of tolerability is higher.

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