Aggressive B-cell lymphomas that are primary refractory to, or relapse after, 
frontline chemoimmunotherapy have a low cure rate with conventional therapies. 
Although high-dose chemotherapy remains the standard of care at first relapse 
for sufficiently young and fit patients, fewer than one-quarter of patients with 
relapsed/refractory disease are cured with this approach. Anti-CD19 chimeric 
antigen receptor (CAR) T cells have emerged as an effective therapy in patients 
with multiple relapsed/refractory disease, capable of inducing durable 
remissions in patients with chemotherapy-refractory disease. Three anti-CD19 CAR 
T cells for aggressive B-cell lymphoma (axicabtagene ciloleucel, 
tisagenlecleucel, and lisocabtagene ciloleucel) are either U.S. Food and Drug 
Administration approved or in late-stage development. All three CAR T cells 
produce durable remissions in 33%-40% of treated patients. Differences among 
these products include the specific CAR constructs, costimulatory domains, 
manufacturing process, dose, and eligibility criteria for their pivotal trials. 
Notable toxicities include cytokine release syndrome and neurologic toxicities, 
which are usually treatable and reversible, as well as cytopenias and 
hypogammaglobulinemia. Incidences of cytokine release syndrome and neurotoxicity 
differ across CAR T-cell products, related in part to the type of costimulatory 
domain. Potential mechanisms of resistance include CAR T-cell exhaustion and 
immune evasion, CD19 antigen loss, and a lack of persistence. Rational 
combination strategies with CAR T cells are under evaluation, including immune 
checkpoint inhibitors, immunomodulators, and tyrosine kinase inhibitors. Novel 
cell products are also being developed and include CAR T cells that target 
multiple tumor antigens, cytokine-secreting CAR T cells, and gene-edited CAR T 
cells, among others.