Maintenance therapy in acute myeloid leukemia: advances and controversies

The last decade has seen steadfast progress in drug development in acute myeloid leukemia (AML) which has moved progressively towards genomic-based therapy. With these advances, outcomes in AML have improved but remains far from satisfactory. One approach towards preventing relapse in AML is to use maintenance therapy in patients, after attaining remission. Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective post-remission therapy that has been proven to reduce the risk of relapse. However, in patients who are ineligible for HSCT or have a high risk of relapse, other effective measures to prevent relapse are needed. There is also a need for post-HSCT maintenance to reduce relapse in high-risk subsets. Over the last 3 decades maintenance therapy in AML has evolved from the use of chemotherapeutic agents to more targeted therapies and better modulation of the immune system. Unfortunately, improvements in survival outcomes as a result of using these agents have not been consistently demonstrated in clinical trials. To derive the optimum benefit from maintenance therapy the time points of therapy initiation need to be defined and therapy must be selected precisely with respect to the AML genetics and risk stratification, prior treatment exposure, transplant eligibility, expected toxicity and the patient's clinical profile and desires. The far-reaching goal is to facilitate patients with AML in remission to achieve a normal quality of life while improving remission duration and overall survival. The QUAZAR trial was a welcome step towards a safe maintenance drug that is easy to administer and showed survival benefit but leaves many open issues for discussion. In this review we will discuss these issues, highlighting the development of AML maintenance therapies over the last 3 decades.