Dr Coombs on Disease Management Strategies in AML

Catherine C. Coombs, MD, associate clinical professor, medicine, University of California, Irvine School of Medicine, discusses strategies for disease classification and management for patients with acute myeloid leukemia (AML).

The AML treatment paradigm has evolved to include several new agents in recent years, Coombs says. However, these advancements are complicated by disparities between AML classification systems, Coombs notes. In an OncLive^® State of the Science Summit™ on hematologic oncology, Coombs and colleagues discussed the traditionally used World Health Organization AML classification system and newer criteria from the International Consensus Classification system.

There are benefits and drawbacks of using several different AML classification systems, Coombs explains. Notably, the variety of, and differences between, systems can confuse both oncologists and patients, Coombs notes. In the future, a unified classification system could simplify disease stratification processes and better inform clinical trial enrollment criteria and outcome assessment, Coombs emphasizes.

The FLT3 inhibitor quizartinib has long been under clinical investigation, Coombs continues. In July 2023, the combination of quizartinib (Vanflyta) and 7 + 3 chemotherapy was FDA approved for the treatment of patients with newly diagnosed, FLT3-ITD–positive AML. This regulatory decision was supported by results from the pivotal phase 3 QuANTUM-First trial (NCT02668653), which were published in The Lancet in 2023, Coombs says. In QuANTUM-First, at a median follow-up of 39.2 months (IQR, 31.9-45.8), patients who received quizartinib achieved a median overall survival of 31.9 months (95% CI, 2.0-not estimable) vs 15.1 months (95% CI, 13.2-26.2) with placebo (HR, 0.78; 95% CI, 0.62-0.98; 2-sided P = .032).

Prior to the FDA approval of quizartinib, midostaurin (Rydapt) in combination with standard cytarabine and daunorubicin induction therapy and cytarabine consolidation therapy was approved in 2017 for patients with newly diagnosed, FLT3-positive AML. Although quizartinib is only indicated for patients with FLT3-ITD mutations, the midostaurin indication is more broad, as this agent can also be used to treat patients with FLT3-TKD mutations, Coombs concludes.