Relapsed acute myeloid leukaemia (AML) is an aggressive blood cancer with a dismal prognosis - durable responses from chemotherapy alone are rare. Chimeric antigen receptor (CAR) modified T-cells (CAR T-cells) have revolutionised outcomes for some types of relapsed leukaemia (notably CD19+ B-lineage acute lymphoblastic leukaemia, or B-ALL), however preliminary clinical response rates in AML with CAR T-cells have been disappointing. This finding is discordant with data indicating anti-AML directed CAR T-cells are highly potent when tested in in vitro and in vivo pre-clinical models. It is not yet understood why clinical responses to CAR T-cells are poor in AML.
This presentation will explore novel approaches to tackle the challenges of CAR T-cell therapy of AML, including novel strategies to mitigate on-target off-tumour haematological toxicity and the potential use of “transplant-plus” approaches in the clinic. The development of new pre-clinical models of AML/ CAR T-cell potency and the potential for combined immunotherapy approaches to tackle myeloid malignancies will also be discussed.