Post-remission therapy in acute myeloid leukemia: Are we ready for an individualized approach?

Abstract

Recent advances in remission induction treatment strategies for acute myeloid leukemia (AML) have improved the rates of complete remission (CR) and overall survival (OS), owing to a concerted effort to tailor therapies toward specific AML subtypes. However, without effective post-remission therapy, most patients will relapse. The extent to which post-remission therapies is individualized in the current paradigm is quite varied. Core binding factor (CBF) AML is typically treated with post-remission high-dose cytarabine (HiDAC) without allogeneic hematopoietic stem cell transplantation (HSCT), whereas those with intermediate or adverse-risk cytogenetics are treated with post-remission cytarabine followed by allogeneic HSCT in CR1 when feasible. A lack of clarity regarding the proper dosing of post-remission cytarabine has made consensus building on dosing and schedule a challenge. CBF AML benefits most from high-dose cytarabine (HiDAC), and dasatinib appears promising as an adjunct for those for KIT-mutated CBF AML. Other than series using CPX-351 or lomustine in older adults, multiagent chemotherapy approaches have resulted in excess toxicity without a survival benefit. Neither hypomethylating agents nor gemtuzumab ozogamicin have shown a material OS benefit. Targeted agents such as FLT3 inhibitors and IDH1/IDH2 inhibitors show potential for the patients who harbor these druggable targets, but few data are available. Many studies evaluating post-remission strategies to target AML in the MRD-positive state are already underway, and these remain a promising area of investigation.

Keywords: AML; Acute myeloid leukemia; CBF; Core binding factor; FLT3; HiDAC; High-dose cytarabine; IDAC; IDH1; IDH2; Intermediate-dose cytarabine; LDAC; Low-dose cytarabine; MRD; Measurable residual disease; Post-remission.