Evolving Treatment Strategies for Elderly Leukemia Patients with IDH Mutations

• Main Authors: Michael J. Buege, Adam J. DiPippo, Courtney D. DiNardo
• Format: Article
• Language: English
• Published: MDPI AG 2018-06-01
• Series: Cancers
• Subjects: acute myeloid leukemia; treatment; elderly; enasidenib; AG-221; ivosidenib; AG-120; venetoclax; ABT-199
• Online Access: http://www.mdpi.com/2072-6694/10/6/187

Acute myeloid leukemia (AML) is a debilitating and life-threatening condition, especially for elderly patients who account for over 50% of diagnoses. For over four decades, standard induction therapy with intensive cytotoxic chemotherapy for AML had remained unchanged. However, for most patients, standard therapy continues to have its shortcomings, especially for elderly patients who may not be able to tolerate the complications from intensive cytotoxic chemotherapy. New research into the development of targeted and alternative therapies has led to a new era in AML therapy. For the nearly 20% of diagnoses harboring a mutation in isocitrate dehydrogenase 1 or 2 (IDH1/2), potential treatment options have undergone a paradigm shift away from intensive cytotoxic chemotherapy and towards targeted therapy alone or in combination with lower intensity chemotherapy. The first FDA approved IDH2 inhibitor was enasidenib in 2017. In addition, IDH1 inhibitors are in ongoing clinical studies, and the oral BCL-2 inhibitor venetoclax shows preliminary efficacy in this subset of patients. These new tools aim to improve outcomes and change the treatment paradigm for elderly patients with IDH mutant AML. However, the challenge of how to best incorporate these agents into standard practice remains.