The complete story of less than complete responses: The evolution and application of acute myeloid leukemia clinical responses

Abstract Complete remission (CR) has long been the critical therapeutic response in acute myeloid leukemia (AML). However, “less than CR” responses have been and continue to be proposed to define clinically meaningful post-therapy outcomes. These responses include CR with incomplete recovery (CRi), CR with incomplete platelet recovery (CRp) and, most recently, CR with partial hematologic recovery (CRh), which has been introduced and subsequently used for regulatory approval. However, the clinical benefits associated with “less than CR” responses have primarily been evaluated in the context of intensive therapies. In an era with sophisticated measurable residual disease (MRD) assessments, including flow-based, cytogenetic and molecular techniques, and an increase in “targeted”, non-intensive therapies, the clinical value of responses that are “less than CR” must be reevaluated. Improvements in the rate of CR has not always led to improvements in OS among older patients. As such, MRD techniques might help define a more stringent response criterion (MRD-negative CR) that might better correlate with OS and should be incorporated in future clinical trials. Here we discuss the evolution of CR and “less than CR” responses, data regarding their clinical benefits, and considerations relevant to response assessments with newer therapies.