Abstract CT021: Tumor-associated immune cell PD-L1 expression and peripheral immune profiling: Analyses from CheckMate 141
Bibliographic record
Abstract
Abstract Introduction: In the phase 3 study CheckMate 141 (NCT02105636), patients with platinum-refractory head and neck squamous cell carcinoma treated with nivolumab (NIVO) had longer median overall survival (OS) (7.5 vs 5.1 months; P=0.01) and a higher objective response rate (all: 13.3 vs 5.8%; tumor PD-L1 ≥1%: 17 vs 1.6%) compared with investigator’s choice (IC) (Ferris et al. NEJM. 2016). This exploratory analysis evaluated the immune profile of patients from CheckMate 141, in context of tumor PD-L1 expression, and assessed the relationship with treatment (txt) outcomes. Methods: PD-L1 expression in tumor and tumor-associated immune cells (TAIC) was analyzed at baseline (n=252) and assessed for association with clinical outcome. Tumor PD-L1 expression was quantitatively assessed using Dako IHC 28-8 pharmDx assay. TAIC PD-L1 abundance (numerous/intermediate, rare) and location (intra/intra-peritumoral, peritumoral) were qualitatively assessed (unvalidated). Peripheral blood (n=36) at baseline and day 43 was assessed for immune cell biomarkers by flow cytometry and analyzed by 2-way ANOVA with Sidak’s multiple comparisons test correction. Results: Abundant PD-L1+ TAICs (numerous/intermediate) were associated with greater median OS with NIVO vs IC in tumors with PD-L1 ≥1% (abundant: 8.7 vs 4.4 months, hazard ratio [HR] and 95% CI 0.44 [0.27, 0.71] and rare: 6.7 vs 4.9 months, HR 0.88 [0.42, 1.86]) and PD-L1 <1% (abundant: 12.7 vs 8.4 months, HR 0.73 [0.38, 1.41] and rare: 3.7 vs 4.6 months, HR 1.02 [0.45, 2.30]). Abundant, but not rare, PD-L1+ TAICs were associated with response to NIVO vs IC in tumors with PD-L1 ≥1% (abundant: 23 vs 0%, odds ratio [OR] and 95% CI 18.98 [1.03, 348.17] and rare: 17 vs 8%, OR 1.73 [0.21, 14.63]) and PD-L1 <1% (abundant: 22 vs 14%, OR 1.61 [0.40, 6.49] and rare: 6 vs 14%, OR 0.39 [0.03, 5.10]). Intra/intra-peritumoral location of PD-L1+ TAICs was associated with greater median OS with NIVO vs IC in tumors with PD-L1 ≥1% (8.2 vs 4.4 months, HR 0.54 [0.33, 0.89]) and PD-L1 <1% (7.1 vs 5.1 months HR 0.63 [0.34, 1.14]). Peritumoral location of PD-L1+ TAICs was associated with greater median OS with NIVO vs IC in tumors with PD-L1 ≥1% (8.7 vs 4.3 months HR 0.55 [0.27, 1.15]) but not PD-L1 <1% (4.3 vs 10.6 months HR 1.72 [0.58, 5.08]). In the circulation, NIVO responders had higher total CD8+ T cells at baseline and on txt (both mean 22.5 vs 12.8%, P=0.04) and lower PD-1+ Tregs at baseline (mean 18.7 vs 33.4%, P<0.01) and on txt (mean 11.7 vs 19.7%, P<0.01) vs non-responders, and lower CTLA-4+ CD8+ T cells on txt vs at baseline (mean 8.2 vs 5.4%, P=0.02). Conclusion: In this exploratory, qualitative immune profile analysis, abundance of PD-L1+ TAICs was associated with higher median OS and greater likelihood of response to NIVO vs IC. Response to NIVO may be associated with higher circulating CD8+ T cells and lower Tregs at baseline, and abundant PD-L1+ TAICs in the tumor microenvironment. Citation Format: Robert L. Ferris, George Blumenschein, Kevin Harrington, Jérôme Fayette, Joël Guigay, A. Dimitrios Colevas, Lisa Licitra, Stefan Kasper, Caroline Even, Francis Worden, Nabil F. Saba, Everett Vokes, Cheryl Ho, Fernando Concha-Benavente, Danielle Greenawalt, Chelsea Jin, Mark Lynch, Makoto Tahara, Robert Haddad, Manish Monga, Henry Kao, Maura Gillison. Tumor-associated immune cell PD-L1 expression and peripheral immune profiling: Analyses from CheckMate 141 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT021. doi:10.1158/1538-7445.AM2017-CT021
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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".