Safety evaluation of axicabtagene ciloleucel for relapsed or refractory large B-cell lymphoma.

ABSTRACT

INTRODUCTION: CD19-directed chimeric antigen receptor (CAR) T-cell therapy is a highly effective therapy for patients with relapsed/refractory large B-cell lymphoma (LBCL) and three CD19 CAR T-cell products (axicabtagene ciloleucel, tisagenlecleucel and lisocabtagene maraleucel) are currently approved for this indication. Despite the clinical benefit of CD19 directed CAR T-cell therapy, this treatment is associated with significant morbidity from treatment-emergent toxicities. AREAS COVERED This Review discusses the safety considerations of axicabtagene ciloleucel in patients with LBCL. This includes discussion of the frequently observed immune-mediated toxicities of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. Additionally, we review CAR T-cell therapy related cytopenias, infection, organ dysfunction and the more recently described hemophagocytic lymphohistiocytosis. EXPERT OPINION A thorough understanding of the toxicities associated with CD19-directed CAR T-cell therapy will facilitate the optimal selection of patients for this therapy. Furthermore, knowledge of preventative measures of CAR T-cell related complications, and early recognition and appropriate intervention will lead to the safe administration of these therapies, and ultimately improved outcomes for our patients.