Dr. Michaelis on Safety Considerations With Venetoclax/Azacitidine in AML

Laura C. Michaelis, MD, associate professor, Medical College of Wisconsin, discusses safety considerations with the combination of venetoclax (Venclexta) and azacitidine in acute myeloid leukemia (AML).

Findings from the phase 3 VIALE-A trial (NCT02993523) demonstrated a 34% reduction in the risk of death with venetoclax/azacitidine vs azacitidine alone in patients with treatment-naïve AML who were ineligible for intensive therapy. Although the regimen appears to be better tolerated compared with more cytotoxic therapies for this patient population, safety considerations are needed, says Michaelis.

Notably, the majority of patients with newly diagnosed AML present with baseline disease-related toxicities, such as night sweats, fatigue, neutropenia, thrombocytopenia, and liver function test abnormalities, Michaelis explains. Over time, treatment with venetoclax/azacitidine can lead to myelosuppression, Michaelis adds.

Traditionally, bone marrow biopsies are not routinely conducted after the first cycle of treatment with single-agent azacitidine or single-agent hypomethylating agents, Michaelis says. It could take up to 6 cycles of therapy for patients to achieve the maximal response and treatment-related cytopenias are generally manageable, so biopsies are not needed initially, Michaelis says. With the combination of venetoclax/azacitidine, obtaining a bone marrow biopsy following cycle 1 of treatment can be useful in determining whether a patient can delay treatment for treatment-related cytopenia, Michaelis says. If the bone marrow biopsy shows that the patient is in remission, delaying treatment could be beneficial, whereas if the patient has active disease, treatment should be continued, concludes Michaelis.