Abstract
Early clinical experience with the use of chimeric antigen receptor (CAR) T-cell therapies for patients with acute myeloid leukemia (AML) has been beset by high rates of toxicities and low rates of response. We convened an international workshop with the goal of bringing investigators in the field of AML-directed CAR T-cell therapy together to facilitate discussion of challenges and to brainstorm potential solutions. Based on discussions at the workshop, it was evident that (1) treating and targeting AML with CAR T cells is associated with unique clinical challenges, and (2) variability in clinical trial design, definitions of toxicities, correlative data collection, and reporting methods hinders the field's ability to compare study outcomes and to develop best practices. Further, details of fundamental CAR T-cell attributes and key correlates of efficacy and toxicity were not uniformly reported in published studies, limiting understanding of barriers to success. These observations led to a concerted team effort in which experts in basic/translational science and clinical investigation from pediatric and adult centers worked together to streamline key attributes of clinical trial design and reporting. Consensus criteria were discussed and agreed upon, leading to the creation of a white paper. These guidelines aim to bolster the overall quality of AML-directed CAR T-cell research, allow for comparisons across trials, and inform the next phase of development of AML-directed CAR T-cell therapies that we hope will improve patient outcomes.