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.
The efficacy and toxicity outcomes of patients with large B cell lymphoma receiving FDA-approved CD19-targeted chimeric antigen receptor (CAR) T cells are largely comparable between pivotal clinical trials and real-world studies.
Certain patient-specific and tumour-specific characteristics, particularly a high pretreatment tumour bulk and/or burden and the presence of inflammatory biomarkers, are associated with inferior efficacy and more severe toxicities.
CAR T cells manufactured from leukapheresis products comprising a higher fraction of more differentiated T cells are associated with inferior efficacy.
Real-world studies provide the opportunity to identify factors associated with outcomes that