Interpreting the clinical outcomes to date for AML-directed CAR T cell therapies

Chimeric antigen receptor (CAR) T therapies hold potential as a new therapeutic approach for relapsed/refractory acute myeloid leukemia (R/R AML), but development has been challenging due to difficulty identifying the optimal targeting antigen. AML exhibits heterogenous and overlapping antigen expression with normal hematopoietic cells, raising concerns for poor efficacy and on-target/off-tumor hematotoxicity. However, it is not clear that these concerns have been fully borne out in available clinical data. Here, we review clinical studies of AML CAR T therapies with a focus on critically evaluating efficacy and toxicities.

Encouraging responses have been reported in a notable proportion of patients in published trials, especially when taking into consideration that patients have treatment-resistant disease after multiple lines of therapy. Rates of cytopenias after AML CAR T therapies vary and there are insufficient data to delineate whether they are due to on-target toxicity or off-target effects such as low marrow reserve and myelosuppressive inflammatory sequelae.

These studies highlight the need for continued optimization of CAR T design and treatment strategies to enhance efficacy and reduce toxicities in AML. Further studies are needed to better understand the frequency/severity of cytopenias after AML CAR T therapies and to clarify the underlying on-/off-target mechanisms.