The combination of the B cell lymphoma 2 inhibitor venetoclax with hypomethylating agents (either decitabine or 5‐azacytidine) represents a significant advance in acute myeloid leukemia (AML) therapy, according research published in the American Journal of Hematology.

Venetoclax-hypomethylating agents combination therapy was recently approved by the U.S. Food and Drug Administration as frontline therapy in patients unfit for intensive chemotherapy. Matthew Mei, MD, of the department of hematology and hematopoietic cell transplantation at the City of Hope Medical Center in Duarte, California, and colleagues examined the latest data on this combination therapy and provided practical management recommendations based on protocol guidelines, published data, and analysis of real-world evidence.

Previous studies have shown that both venetoclax and hypomethylating agents have single-agent activity in AML. However, they appear to be more effective when combined, suggesting a potential synergy. Recent data indicate that the rate of complete remission (CR) or CR with incomplete count recovery may exceed 70% for frontline venetoclax‐hypomethylating agents. Similar responses have been demonstrated across patients with various genetic subtypes of AML, including those who have responded poorly to conventional chemotherapy.

“With this combination regimen, it is easier to treat older and frail patients. It is highly effective,” said Mark James Levis, MD, PhD, program leader of the hematologic malignancies and bone narrow transplant program at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in Baltimore, Maryland, in an interview with Hematology Advisor.

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He and his colleagues enrolled 30 patients in clinical trials studying venetoclax-hypomethylating agents and have treated an equal number of patients off label. In both the frontline and relapsed/refractory settings, venetoclax-hypomethylating agents has demonstrated significant efficacy in treating patients with adverse prognostic factors such as TP53 mutations.

“It is a great regimen that is changing outcomes, in my view,” Dr Levis told Hematology Advisor. He noted that many patients can now benefit from less intensive chemotherapy regimens, which may ultimately lower morbidity and mortality. “Usually when they present, patients get hammered with chemotherapy and infections are a real issue. Older patients couldn’t handle it. [Clinicians] couldn’t do bone marrow transplants in older patients, but now they can because it is better. [The patients] don’t have to get so much chemo upfront.”