Dr Borate on Dose Optimization and Toxicity Management in Older Patients With AML

“We all want novel breakthroughs; we all want the next best thing that can cure your disease. The reality is, for a lot of our older patients, the treatments that we currently have are treatments that are prohibitive for them because of toxicities…It’s just as important to optimize the dosing and toxicities of existing treatments for our older patients with AML as it is to have new, amazing, and curative breakthroughs.”

Uma Borate, MBBS, a physician and professor of hematology in the Department of Internal Medicine at The Ohio State University Comprehensive Cancer Center—James, discussed the need to optimize dosing and reduce toxicities with existing therapies for older patients with acute myeloid leukemia (AML).

Many older patients with AML are not candidates for curative stem cell transplant and instead receive indefinite treatment with regimens such as venetoclax (Venclexta) plus a hypomethylating agent, such as azacitidine (Vidaza), Borate said. While developing novel, potentially curative therapies for AML remains a goal, she said it is equally important to determine the right dose of currently approved agents to reduce toxicity and preserve efficacy, since prolonged exposure to toxic regimens can compromise older patients’ quality of life and outside the clinic.

Borate also raised the question of whether fixed-duration, time-limited treatment could be applied in AML. She proposed giving therapy for a defined period, then stopping and monitoring disease or measurable residual disease status, rather than continuing treatment indefinitely. Borate described fixed-duration regimens as a potential next frontier worth investigating in older patients with AML.

Borate concluded by pointing to a phase 1 trial (NCT03013998), led by Joshua F. Zeidner, MD, of the UNC Lineberger Comprehensive Cancer Center, evaluating the triplet of azacitidine, venetoclax, and revumenib (Revuforj) in newly diagnosed patients 60 years and older with NPM1-mutated or KMT2A-rearranged AML. Borate noted that adding a third agent to the azacitidine and venetoclax backbone is a novel strategy, and this trial will help clarify both the effectiveness and the toxicity of this triplet regimen, calling it a study to watch.