Safety and efficacy of axicabtagene ciloleucel in refractory large B-cell lymphomas

Abstract

Aggressive large B-cell lymphomas represent a diverse population of diseases that are typically treated with anti-CD20 based immunochemotherapy. While this treatment is effective for a large proportion of patients, those that become refractory to induction therapy or experience disease relapse suffer an inferior overall prognosis, and novel treatment options are needed. Adoptive T-cell immunotherapy in the form of chimeric antigen receptor (CAR) T-cell therapy is one of the most revolutionary breakthroughs in the past several decades for the treatment of relapsed/refractory aggressive large B-cell lymphomas. Based on data from the pivotal ZUMA-1 study, axicabtagene ciloleucel (axi-cel) became the first-in-class anti-CD19 directed CAR T-cell therapy approved for patients with diffuse large B-cell lymphoma and other aggressive B-cell lymphoma variants. In this review, we provide an overview of CAR T-cell therapy, including its biology, manufacturing, and treatment course. In addition, we highlight the available efficacy data, review pertinent safety concerns, including cytokine release syndrome and neurologic toxicity, as well as provide an overview of emerging therapeutic strategies in the cellular therapy arena.