4 1BB based chimeric antigen receptor T cell therapy targeting CD19 demonstrates the most favourable efficacy and safety profile in relapsed or refractory B cell precursor acute lymphoblastic leukaemia, according to a large meta-analysis. The findings provide comparative insight into construct design and clinical outcomes across 40 trials involving 1,540 patients.
Comparative Efficacy Across Constructs
Chimeric antigen receptor T cell therapy (CAR T), has transformed the management of relapsed or refractory B cell precursor acute lymphoblastic leukaemia, achieving high remission rates across multiple constructs. However, durability remains a challenge, with many patients relapsing after initial response.
In this systematic review and meta-analysis, the pooled complete remission rate was 83.4%, with moderate heterogeneity: I2=49%. The minimal residual disease negative complete remission or complete remission with incomplete haematologic recovery rate reached 92.7%: I2=48%.
Construct design significantly influenced outcomes. Products incorporating a 4-1BB co stimulatory domain achieved higher minimal residual disease negative remission rates than those using CD28: 94.0% versus 84.4%; p=0.048. These data indicate a potential advantage in depth of response with 4 1BB based constructs.
Target Selection and Safety Profile
Target antigen also affected efficacy. CAR T cell therapies directed against CD19 alone or dual CD19 and CD22 targets produced higher minimal residual disease negative remission rates compared with CD22 targeted products alone.
In addition to efficacy differences, 4 1BB constructs were associated with a lower incidence of immune effector cell associated neurotoxicity syndrome compared with CD28 based designs, suggesting a more favourable safety profile.
Implications For Leukaemia
Taken together, these findings suggest that 4 1BB based CAR T cell therapy targeting CD19 provides the optimal balance of efficacy and safety in relapsed or refractory B cell precursor acute lymphoblastic leukaemia. As construct design continues to evolve, these comparative data may inform clinical decision making and future therapeutic development in this high-risk population.
Reference
Navarro V et al. CAR T-cell therapy in patients with acute lymphoblastic leukemia: a systematic review and meta-analysis. Bone Marrow Transplantation. 2026; https://doi.org/10.1038/s41409-026-02803-6.
