Novel Therapies for Acute Myeloid Leukemia: Are We Finally Breaking the Deadlock?

Acute myeloid leukemia (AML) is one of the best studied malignancies, and significant progress has been made in understanding the clinical implications of its disease biology. Unfortunately, drug development has not kept pace, as the ‘7+3’ induction regimen remains the standard of care for patients fit for intensive therapy 40 years after its first use. Temporal improvements in overall survival were mostly confined to younger patients and driven by improvements in supportive care and use of hematopoietic stem cell transplantation. Multiple forms of novel therapy are currently in clinical trials and are attempting to bring bench discoveries to the bedside to benefit patients. These novel therapies include improved chemotherapeutic agents, targeted molecular inhibitors, cell cycle regulators, pro-apoptotic agents, epigenetic modifiers, and metabolic therapies. Immunotherapies in the form of vaccines; naked, conjugated and bispecific monoclonal antibodies; cell-based therapy; and immune checkpoint inhibitors are also being evaluated in an effort to replicate the success seen in other malignancies. Herein, we review the scientific basis of these novel therapeutic approaches, summarize the currently available evidence, and look into the future of AML therapy by highlighting key clinical studies and the challenges the field continues to face.