The safety and efficacy of immune checkpoint blockade in children, adolescents, and young adults: A systematic review and meta-analysis
Bibliographic record
Abstract
Immune checkpoint blockade (ICB) has changed the treatment landscape for many types of adult cancer. However, for children, adolescents, and young adults (CAYAs) clinical experience lags behind that of adults. Therefore, we performed a systematic review and meta-analysis to evaluate the safety and efficacy of ICB in the CAYA population. We searched PubMed, Embase, and Cochrane Library databases for clinical trials evaluating ICB therapies for cancer in CAYA patients. We pooled the incidences of treatment-related adverse events (TRAEs), objective response rates (ORRs), stable disease (SD), and their corresponding confidence intervals (CIs). For the ORR and TRAE endpoints, we performed a subgroup analysis of each drug (PD-1, PD-L1, and CTLA-4) and tumor type. 15 trials were included, comprising 797 patients (median age ranging from 6.5-16.0 years). All-grade TRAE rate of 66% was found (95% CI 60-71), while the proportion of grade 3/4 TRAEs was 19% (95% CI 14-27). For tumor type subgroup analysis of all-grade TRAEs and grade 3/4 TRAEs, solid tumors had the highest rates, 92% (95% CI 41-99) and 32% (95% CI 11-63), respectively. Fatigue, anemia, and nausea were the most frequently reported TRAEs. The ORR was 13% (95% CI 5-27). In subgroup analyses, PD-1 inhibitors and Hodgkin Lymphoma had the highest ORR, with 25% (95% CI 8-56) and 59% (95% CI 23-87), respectively. SD was noted in 21% (95% CI 14-30) of patients. Overall, ICB is well tolerated in CAYA patients with different cancer types, and certain subsets of CAYA cancer are ICB-responsive. • We accessed CAYA patients with cancer treated with immune checkpoint blockade (ICB). • This systematic review and meta-analysis included 15 studies and 797 CAYA patients. • ICBs are well tolerated across various cancer types in CAYA patients. • Certain cancer subtypes in CAYA patients show a positive response to ICBs. • CAYA patients are likely to gain significant benefit from ICB therapy.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.010 | 0.002 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".