Impact of CAR-T Dosing on Young Patients with Leukaemia - EMJ

Impact of CAR-T Dosing on Young Patients with Leukaemia

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IMPROVED outcomes for young patients with B cell acute lymphoblastic leukaemia (B-ALL) treated with doses of CD19-directed chimeric antigen receptor T cell (CAR-T) immunotherapy, tisagenlecleucel, at the higher end of the approved safety range, were reported following a recent retrospective analysis.

The approved dose range for tisagenlecleucel in young patients with B-ALL is broad, at 0.2–5×106 CAR T cells/kg for patients weighing 50 kg and 10–250×106 CAR T cells/kg for those weighing >50 kg. This can lead to dosing uncertainty and lack of clarity regarding repeat doses. 

To determine how CAR T cell dose impacts patient outcomes, Liora Schultz, Stanford Medicine Children’s Health and Lucile Packard Children’s Hospital Stanford, Stanford University, Palo Alto, California, USA, and colleagues, analysed data from the Pediatric Real World CAR Consortium (PRWCC). In total, 180 patients aged 26 years with relapsed or refractory B-ALL who had undergone apheresis for CAR-T manufacturing between August 2017 and March 2020 were included. The study aimed to evaluate dose of tisagenlecleucel against overall survival (OS), event-free survival (EFS), and relapse-free survival, as well as treatment safety. Patients were categorised into four dose levels, with dose level one being the lowest dose and dose level four being the highest. 

The authors found that patients who received doses at the higher end of the approved safety range had significantly longer OS (p=0.0310), relapse-free survival (p=0.0045), and EFS (p=0.0079) than those who received lower doses. The OS hazard ratio for dose level four versus dose level one was 0.26 (95% confidence interval: 0.10–0.69). Additionally, the researchers also found that EFS was longer for patients who received dose level four compared with to dose level one (hazard ratio: 0.33; 95% confidence interval: 0.17–0.65). These results highlight the impact of higher dosing on increasing OS and lengthening EFS. Furthermore, increased doses had no association with increased neurotoxicity, Grade 3 or higher adverse events, or treatment-related cytokine release syndrome. 

Schultz concluded that their findings supported “the use of higher CAR T cell dosing, within the approved dose range,” and stated that higher dosing was “associated with improved survival, without statistically significant increases in key CAR-related toxicities.” 

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