The role of immune checkpoint blockade in children, adolescents, and young adults: A systematic review and meta-analysis.
Bibliographic record
Abstract
10057 Background: Immune checkpoint blockade (ICB) has changed the treatment landscape for many types of adult cancer. However, while certain subsets of cancer in children, adolescents, and young adults (CAYA) are ICB-responsive, ICBs are less routinely used in clinical practice, thus 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. Methods: PubMed, Cochrane and Embase libraries were systematically searched for clinical trials evaluating ICB therapies for cancer in CAYA patients. We excluded reviews, case reports, observational studies, retrospective studies, studies with overlapping populations, trials with no outcomes of interest, and studies enrolling the adult populations (>40 years). We pooled the prevalence of treatment-related adverse events (TRAE), objective response rate (ORR), stable disease (SD), and their corresponding 95% confidence intervals (95% CI). For ORR and TRAE endpoints, we performed a subgroup analysis of each drug (PD-1, PD-L1 and CTLA-4) and each tumor type. A comparative analysis of the reported median overall survival (OS) and progression-free survival (PFS) was also completed. Statistical analysis was performed using R software version 4.3.1 and heterogeneity was evaluated through I2 statistics. Results: From 3,753 initial studies, 15 clinical trials were included, comprising 797 patients with median age ranging from 6.5 to 16.0 years (1-30 years) and multiple types of hematologic and solid malignancies. An all-grade TRAE rate of 66% was found (95% CI 60-71), while the proportion of grade 3/4 TRAE was 19% (95% CI 13-27). In the tumor type subgroup analysis for all-grade TRAE and grade 3/4 TRAE, solid tumors had the highest rates; 92% (95% CI 41-99) and 50% (95% CI 14-42), respectively. Central nervous system tumors had all-grade and grade 3/4 TRAE rates of 61% (95% CI 53-68) and 21% (95% CI 12-33), respectively. Fatigue, anemia, and nausea were the most frequently reported TRAE. The ORR was 13% (95% CI 5-27) (82 of 531 patients). For drug class and tumor type subgroup analysis, PD-1 inhibitors and lymphoma presented the highest proportion of 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 (97 of 467 patients). Median OS, available for 300 patients, ranged from 4.4 to 23.7 months, while median PFS, available for 299 patients, ranged from 1.2 to 6.2 months. Conclusions: This study suggests that ICB is well tolerated in CAYA patients with different cancer types. As previously reported in the literature, certain subsets of CAYA cancer are ICB-responsive. This pooled safety data supports the continued investigation of ICB in CAYA patients most likely to benefit from ICB therapy, including advancing ICB into combination strategies.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.011 | 0.022 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.016 | 0.032 |
| Bibliometrics | 0.007 | 0.009 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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 source (direct Gemma or distilled Codex), 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".