Safety and efficacy of interleukin-6 blockade for immune-related adverse events: A systematic review and meta-analysis.
Bibliographic record
Abstract
e24149 Background: Interleukin-6 blockade (IL-6) - tocilizumab and sarilumab - have shown promising results for steroid-refractory immune-related adverse events (irAEs) in cancer patients treated with immune-checkpoint inhibitors (ICI). However, the ideal scenario for IL-6 therapy use is not well established. Hence, we conducted a systematic review and meta-analysis to investigate the safety and efficacy of IL-6 blockade for patients with ICI-associated irAEs. Methods: PubMed, Embase, and Cochrane databases were searched for studies including at least five patients with ICI-associated irAEs treated with IL-6 blockade. The main outcomes were safety and efficacy, measured as clinical improvement (resolution or improvement of irAEs or steroid taper to < 10mg daily), C-reactive protein (CRP) level changes, and elevated IL-6 levels. Analyses using random-effects model were done in R Software. Heterogeneity was assessed using I2. Results: Eight studies with 202 patients were included: 1 clinical trial, 3 multicenter, and 4 single-center observational studies. The median age was 63 years (30-81), and 59% were male. Melanoma was the predominant tumor type (n = 78, 38.6%), followed by lung (n = 67, 33%), renal cell carcinoma (n = 21, 10%), bladder cancer (n = 12, 6%), and others. Monotherapy with ICI, targeting PD-1, PD-L1, or CTLA-4, was given to 77% of patients, while 23% had combination ICI therapy. Follow-up ranged from 6 to 23 months. Most patients received prior steroids (85%) or steroid-sparing immunosuppression (24%). Pooled analysis of all patients showed an overall clinical improvement rate of 87.9% (95%CI 78.7 to 95.1, I2= 44%). Clinical improvement with IL-6 blockade was significantly higher in patients with cytokine release syndrome (CRS, 100%) and rheumatic irAEs (88%) compared to other irAEs (p < 0.01, Table 1). At the time of irAEs, the median CRP level was 109.3 (11.5 to 233), which decreased to 17 (1 to 60) after IL-6 blockade. The frequency of baseline elevated IL-6 level was 90.6% (95%CI 68 to 100, I2= 80%). Grade 3 or 4 IL-6-related adverse events were reported in 11% (17/151) of patients and included neutropenia (n = 6), increased liver transaminase levels (n = 4), and gastrointestinal perforation (n = 2). Conclusions: This systematic review and meta-analysis provides evidence for the use of IL-6 blockade for steroid-treating refractory irAEs associated with ICI. The vast majority of patients with steroid-refractory CRS and rheumatic irAEs were successfully treated with anti-IL6 therapy.[Table: see text]
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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 | 0.013 | 0.025 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.018 | 0.037 |
| Bibliometrics | 0.007 | 0.008 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".