Can modified lymphodepletion before tisagenlecleucel improve outcome in high-risk patients with large B-cell lymphoma?

Lymphodepletion (LD) is a critical component of chimeric antigen receptor T-cell (CAR T-cell) therapy, maximizing the engraftment, efficacy and long-term survival of infused cells [ 1 ]. Although these drugs provided a therapeutical breakthrough, notably in patients with non-Hodgkin lymphoma (NHL), less than half of them achieve a durable response and the prognosis of post CAR T-cell relapse is very poor [ 2 , 3 ]. Mechanisms contributing to CAR T-cells treatment failure include disease-related characteristics (total metabolic tumor volume [TMTV], lactate dehydrogenase [LDH] and C-reactive protein levels, performance status and targeted antigen loss), as well as CAR T-cell-related factors (poor T-cell fitness, T-cell exhaustion, lack of persistence and type of costimulatory molecules in the CAR construct) [ 1 ].