While CAR T-cells are a potentially revolutionary therapy option across a variety of cancer types, their associated side effects include cytokine release syndrome (CRS) and neurotoxicity. Here, Stephan Grupp, MD, PhD, of the Childrens Hospital of Philadelphia, Philadelphia, PA, discusses what influences the intensity of these adverse reactions at the American Society of Oncology (ASCO) 2018 Annual Meeting, held in Chicago, IL. In acute lymphoblastic leukemia (ALL), CRS appears to increase in proportion with disease severity. However, in lymphoma overall toxicity is generally lower, though there does seem to be increased toxicity with axicabtagene ciloleucel compared to tisagenlecleucel.