Acute myeloid leukemia induction in the age of novel therapeutic agents

Abstract

Acute myeloid leukemia (AML) is a malignant neoplasm of the myeloid lineage characterized by the uncontrolled proliferation of immature myeloid blasts in the bone marrow and peripheral blood. AML is a heterogenous disease which occurs across the age spectrum, although with an increasing incidence with age. For decades, first-line, curative-intent therapy has been based on intensive therapy with anthracycline (typically daunorubicin or idarubicin) plus cytarabine (3+7), followed by additional consolidative chemotherapy and/or allogeneic stem cell transplantation. While improvements over the decades in overall survival have been observed, until recently this has been driven largely by advancements in supportive care leading to reduction in treatment-related mortality and allowing a greater proportion of patients (particularly older individuals) to safely undergo intensive therapy induction and consolidation. Despite this, five-year overall survival (OS) rates in older individuals are as low as 5% (age > 70). Although OS for patients age 15-39 is now in the range of 50%-60%, a large portion of patients still succumb to their disease. Cytogenetic and molecular profiling has led to defined risk categories, and complete risk stratification for all patients eligible for intensive therapy is crucial to aiding in the selection of optimal induction and post- remission therapy. In recent years, an improved understanding of AML biology and genetics has led to the approval of a number of novel therapies for patients deemed fit and unfit for intensive therapy, which may finally be moving the needle beyond 3+7. This article will review a current approach to AML induction patients eligible for intensive therapy, with a focus on the utilization of available novel agents.