1. In two phase 1 studies, allogenic anti-CD19 CAR T cell (UCART19) treatment showed a manageable safety profile with relapsed or refractory B-cell acute lymphoblastic leukemia.
2. Allogenic anti-CD19 T cells demonstrated antileukemic activity in both children and adults.
Evidence Rating Level: 2 (Good)
Study Rundown: Although autologous anti-CD19 chimeric antigen receptor (CAR) T cells have demonstrated efficacy in relapsed or refractory CD19-positive B-cell acute lymphoblastic leukemia (B-ALL), they are challenging and costly to produce. While, allogenic versions of CAR-T-cell products exist, they are currently hindered by potential safety concerns. UCART19 is an allogenic CAR-T-cell product that has shown efficacy and safety in a small sample of two children and one adult with relapsed B-ALL. Based on these results, two open-labelled, phase 1 studies were launched for patients with relapsed or refractory B-ALL: the PALL trial for children, and the CALM trial for adults. This report is a combination of both trials, which are ongoing at the time of publication. Overall, the most common adverse events reported were cytokine release syndrome (91% of patients), infections (62%) and neurotoxicity (38%). Several grade 3 or higher events occurred, including cytopenia (75% at day 28 post-treatment) and cytokine release syndrome (14%). The overall response rate was 67% for the pooled cohort and 71% were negative for minimal residual disease. An important consideration in this trial when considering pooled results is that lymphodepletion regimens varied between participants, although separate analyses were done for each group.
Relevant Reading: Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia.
In-Depth [randomized controlled trial]: These two open-label, non-randomized, ongoing phase 1 trials took place in seven centers across France, the United Kingdom and the USA. A total of 21 patients with relapsed or refractory CD19-positive B-ALL received treatment with UCART19, with 7 children (aged 6 mo-18 years) in the PALL trial and 14 adults (aged 16-70 years) in the CALM trial. The primary endpoint of both trials was adverse events, and secondary endpoints included objective response rate, progress-free survival and overall survival. Patients’ previous treatments were recorded; a median of four (IQR 3-5) was recorded before receiving the trial treatment. The dose of UCART19 received varied according to the patients’ clinical parameters. Overall, the most common adverse events reported were cytokine release syndrome (n=19, 91% of patients), infections (n=13, 62%) and neurotoxicity (n=8, 38%). Grade 3 or greater events included cytokine release syndrome (n=3), infections (n=8), prolonged cytopenia (n=6,) and tumor lysis syndrome (n=2). Two deaths in the CALM trial were associated with dose-limiting UCART19 toxicity. UCART19 showed rapid expansion in-vivo which peaked around 14 days and declined by day 28. An overall response rate of 67% (95% confidence interval [CI] 45-83, n=14) was seen for the pooled cohort with 71% (95% CI 45-88%) being negative for minimal residual disease. Progression-free survival at 6 months was 27% (95% CI 10-47%) and 6-month overall survival was 55% (95% CI 32-74%).
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