Meta-analysis compares CAR T-cell constructs in 1540 relapsed/refractory B-ALL patients

This systematic review and meta-analysis examined the efficacy and safety of different CAR T-cell constructs in relapsed/refractory B-cell precursor acute lymphoblastic leukemia (R/R B-ALL). The analysis included 40 clinical trials with a total of 1540 patients, comparing various CAR T-cell constructs against each other rather than against standard therapies. Study setting, follow-up duration, and primary outcome were not reported.

The pooled complete remission rate across all constructs was 83.4% (I²=49%), while the minimal residual disease-negative complete remission rate was 92.7% (I²=48%). When comparing specific construct characteristics, 4-1BB co-stimulatory domain constructs demonstrated higher MRD-negative CR/CRi rates than CD28 constructs (94.0% vs 84.4%, p=0.048). CAR T-cell products targeting CD19 or CD19/CD22 also showed higher MRD-negative CR/CRi rates than those targeting CD22 alone, though specific numbers were not reported.

Safety data including adverse events, serious adverse events, discontinuations, and tolerability were not reported in the available evidence. The analysis has several limitations: funding sources and conflicts of interest were not reported, and the durability of responses remains a major challenge with many patients experiencing relapse after initial remission. For clinical practice, this meta-analysis suggests associations between CAR T-cell construct characteristics and efficacy outcomes, but direct comparisons between specific products require careful interpretation given the heterogeneity across studies.