Association of an immune gene signature with pathologic response and outcome after neoadjuvant pembrolizumab (pembro), compared to neoadjuvant chemotherapy (NAC), in muscle-invasive bladder cancer (MIBC).
Bibliographic record
Abstract
533 Background: In the PURE01 study (NCT02736266), neoadjuvant pembro resulted in 42% pathologic complete responses (pT0) in patients (pts) with MIBC. In this study, we investigated immune transcriptome signatures and molecular subtyping as potential predictors of pembro efficacy. Methods: Pts enrolled in the PURE01, which is still recruiting pts in its amended design, had predominant urothelial carcinoma histology and stage cT≤4N0 MIBC. Biomarker analyses included transcriptome profiling for 78 pts. A cisplatin-based NAC cohort of 140 cT≤4N0 MIBC pts was used for comparison. The association of Immune190, immune hallmark RNA signatures and molecular subtypes (TCGA, Consensus classifier, Genomic subtyping classifier [GSC]) was evaluated with respect to pT0 and recurrence-free survival (RFS). Multivariable logistic regression analyses (MVA) were used adjusting for the clinical T-stage and gender. Results: The Immune190 signature was significant for pT0 on MVA (OR: 1.54, 95%CI: 1.1-2.3, p=0.02) in the PURE01 cohort, but not in NAC cohort (OR: 0.96, 95%CI: 0.8-1.2, p=0.73). The hallmarks for IFN-γ (OR: 1.10, 95%CI: 1-1.2, p=0.007) and IFN-α response (OR: 1.07, 95%CI: 1-1.1, p=0.009) were also associated with pT0 for PURE01, but not for NAC (IFN-γ: OR: 0.99, 95%CI: 0.9-1.1, p=0.846 and INF-α: OR: 0.99, 95%CI: 0.95-1.04, p=0.806). In PURE-01, patients with Immune190 scores >0.35 had 100% 2-y RFS vs 80% of those with ≤0.35; no difference was observed in NAC pts, as well as for the other hallmarks in both groups. The neuroendocrine (NE)-like subtype had the worst 2-y RFS in all three subtyping models (33%, p<0.01) whereas the GSC Claudin-low subtype had the best outcome with no recurrences within 24 months. The other subtypes had RFS ranging from 75-86% in TCGA, 53-89% in Consensus, and 74-92% in the GSC. Conclusions: We found RNA Immune190 signature was reliably associated with response and outcome after neoadjuvant pembro. Molecular subtyping revealed special subtypes with outlier outcomes. These data suggest RNA profiling may provide a potential tool for personalizing the neoadjuvant therapy approach. Clinical trial information: NCT02736266.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".