Efficacy and Safety of Chimeric Antigen Receptor T-Cell Therapy in Children, Adolescents, and Young Adults with Relapsed or Refractory Solid Tumors: A Systematic Review and Meta-Analysis

<title>Abstract</title> <p>Purpose Chimeric antigen receptor T-cell (CAR-T) therapy has shown remarkable success in pediatric hematological malignancies, but its efficacy and safety in pediatric and adolescent solid tumors have not been systematically evaluated. This meta-analysis aimed to assess the antitumor activity and toxicity of CAR-T therapy in this population. Methods Two independent reviewers systematically searched electronic databases from inception to December 31, 2025. We included clinical studies (phase I/II trials and cohort studies; sample size ≥ 3) that enrolled patients aged ≤ 39 years with relapsed/refractory solid tumors treated with CAR-T cells. Pooled objective response rates (ORR) and the incidence of severe adverse events were calculated using random-effects models. Results Eighteen studies comprising 251 treated patients (209 evaluable for efficacy) were included. The pooled overall ORR was 18% (95% CI: 6%–33%). Neuroblastoma (NB) and central nervous system tumors were the most common tumor types; NB showed the highest ORR (27%), although the difference between tumor types was not statistically significant (P = 0.33). Exploratory subgroup analyses suggested that CAR generation, lymphodepletion, culture duration, and transduction efficiency were associated with efficacy (P &lt; 0.05). The pooled incidences of grade ≥ 3 cytokine release syndrome and neurotoxicity were 2.67% and 1.19%, respectively. Conclusion CAR-T therapy demonstrates modest but measurable antitumor activity in children and young adults with relapsed/refractory solid tumors, with an overall ORR of approximately 18%. NB appears relatively more responsive, although efficacy remains substantially lower than that reported for hematologic malignancies. Exploratory subgroup analyses suggest that third-generation CAR-T cells, lymphodepletion, prolonged culture duration, and higher transduction efficiency are associated with higher response rates. Severe CRS and neurotoxicity were uncommon, indicating a generally manageable safety profile. Given the small sample sizes and substantial heterogeneity of the included phase I trials, prospective multicenter studies are needed.</p>