Outcome correlates of approved CD19-targeted CAR T cells for large B cell lymphoma

CD19-targeted chimeric antigen receptor (CAR) T cells have provided a breakthrough in the treatment of patients with relapsed and/or refractory large B cell lymphoma (LBCL). Currently, three CD19-targeted CAR T cell products are approved by the FDA and various other regulators for the treatment of patients with LBCL: axicabtagene ciloleucel, tisagenlecleucel and lisocabtagene maraleucel. Response rates following infusion of these CD19-targeted CAR T cells have been promising; however, approximately half of treated patients show relapse within 2 years. Furthermore, receiving these agents can be associated with serious toxicities, including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. In this Review, we summarize the factors associated with the efficacy, including response and survival outcomes, and toxicity of CD19-targeted CAR T cells in pivotal clinical trials and large real-world datasets describing the outcomes of patients with LBCL who received treatment with these products. CD19-targeted CAR T cells have transformed the management of patients with relapsed and/or refractory large B cell lymphoma, and these therapies are increasingly being administered as earlier-line therapies. Nonetheless, the prognosis of these patients is often difficult to predict, with various prospective and real-world studies suggesting that a wide range of factors are associated with treatment outcomes. In this Review, the authors summarize these various associations as well as their implications for patient selection and management.