Abstract IA03: Immune Related Toxicities Associated with Immunotherapies

Abstract

Chimeric antigen receptor T-cell (CART) therapy has revolutionized care for many pediatric cancers, especially relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). Although CART are highly effective, they can induce severe toxicities. The most common severe adverse events associated with CART are cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS). These toxicities can occur on a spectrum of severity from mild self-limited illness to severe, life-threatening conditions. In patients with high disease burden, severe CRS requiring intensive care occurs in up to 50% of patients with severe ICANS occurring in 25% of patients. Severe CRS can be managed with blockade of IL-6 receptor with tocilizumab. However, strategies to prevent severe CRS in high disease burden patients are needed. Treatment of severe ICANS relies on steroids, and effective targeted therapies are needed. In this talk, we will review novel insights in to the immunopathology of severe CRS and ICANS. We will discuss emerging toxicities, with a focus on immune effector cell associated hemophagocytic-like syndrome (IECHS). We will discuss different patterns of toxicities observed in novel CART targets or new indications. Finally, we will discuss potential management strategies for immune toxicities and future development of safer CART.