Table 2_Efficacy and safety of immunotherapy in pediatric malignant brain tumors: a systematic review and exploratory meta-analysis.docx

Compared with vaccines, non-vaccine immunotherapy did not improve OS (pooled HR 1.14, 95% CI 0.99–1.31; I² 43%) or OS12 (HR 1.13, 95% CI 0.95–1.34; I² 65%). Subgroup analyses showed comparable OS for CAR-T therapies (OS HR 1.09, 95% CI 0.89–1.34) and checkpoint/systemic therapies (OS HR 1.14, 95% CI 0.96–1.36), or oncolytic/viral therapies (OS HR 1.51, 95% CI 0.81–2.84). Severe neurotoxicity differed substantially by modality.

No grade ≥3 neurotoxicity occurred in vaccine studies. In contrast, pooled non-vaccine therapies showed a markedly increased risk (OR 19.66, 95% CI 6.78–57.02; I² 60%). CAR-T therapies (OR 57.95, 95% CI 16.15–207.98) and oncolytic/viral approaches (OR 69.41, 95% CI 17.00–283.33) had the highest risk, whereas checkpoint/systemic therapy showed a lower, non-significant increase (OR 2.26, 95% CI 0.77–6.60).</p>Conclusions<p>Across pediatric immunotherapy trials, survival outcomes were comparable to vaccine-based approaches, but neurotoxicity varied markedly by modality.

Cellular and oncolytic therapies carry a substantial neurologic risk that must be balanced against uncertain survival benefit in future trial designs.</p>