Management of adverse events in young adults and children with acute B-cell lymphoblastic leukemia receiving anti-CD19 chimeric antigen receptor (CAR) T-cell therapy.

Abstract

With impressive clinical advancements in immune effector cell therapies targeting CD19, chimeric antigen receptor (CAR) T-cell therapy has emerged as a new paradigm for treating relapsed/refractory B-cell malignancies. Currently, three second-generation CAR T-cell therapies have been approved, of which only tisagenlecleucel (tisa-cel) is approved for treating children and young adults with B-cell acute lymphoblastic leukemia (ALL) with durable remission rates of approximately 60‒90%. Although CAR T-cell therapies are considered to treat refractory B-ALL, they are associated with unique toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The severity of CAR T-cell therapy toxicities can vary according to several clinical factors. In rare cases, severe CRS can progress to a fulminant hyperinflammatory syndrome known as hemophagocytic lymphohistiocytosis, which has a poor prognosis. The first-line treatments for CRS/ICANS include tocilizumab and corticosteroids. When severe CAR T-cell toxicity is resistant to first-line treatment, an additional approach is required to manage the persistent inflammation. In addition to CRS/ICANS, CAR T-cell therapy can cause early and delayed hematological toxicity, which can predispose patients to severe infections. The use of growth factors and anti-infective prophylaxis should follow institutional guidelines according to patient-specific risk factors. This review provides a thorough summary of updated practical recommendations for managing acute and delayed adverse effects following anti-CD19 CAR T-cell therapy in adults and children.