Abstract 1909P
Background
The translational study NIVOREN GETUG-AFU 26 explored baseline cytokine correlation with outcomes under nivolumab in patients with metastatic renal cell carcinoma. We previously identified five cytokines (IL-6/IL-8/IL-7/VEGF/4-1BB) as potential serum-derived biomarkers of immune checkpoint inhibitors outcomes (N=80), subsequently validated (N=233), we confirmed a significant negative association between IL-6/IL-8/VEGF/BAFF/CXCL13 and worse OS (Carril-Ajuria et al. 2022). In this report, we present the baseline cytokine concentrations according to the line of treatment and investigate their additional prognostic value.
Methods
During the trial, blood samples were collected prospectively. Using the MSD-assay, we measured a panel of eight cytokines (VEGF, VCAM-1, IL-6, IL-7, IL-8, BAFF, 4-1BB, and CXCL13) at baseline. We evaluated the median cytokine levels using the Kruskal-Wallis test. The patients were categorized based on whether they underwent a single line of treatment or multiple lines of treatment.
Results
Overall, 353 patients were included in our analysis among 720 patients treated with nivolumab in the trial. Of these patients, 205 had received only one line of prior treatment, while 148 had received two or more lines of prior treatment. We found that patients who had undergone multiple lines of treatment had significantly higher levels of two cytokines, IL-6 and BAFF. IL-6 is known to be associated with protumoral inflammation and neutrophil activation, while BAFF regulates the trafficking and maturation of B cells.
Table: 1909P
| Cytokines Median (pg/ml) | 1 line of prior systemic therapy N=205 | ≥ 2 lines of prior systemic therapy N=148 | Kruskal-Wallis test |
| IL-6 | 2.8 (0,4 - 276,1) | 3,9 (0,5 - 802,7) | P=0.014 |
| IL-7 | 6,8 (1,4- 29,3) | 6.7 (1,9 – 29,7) | P=0.372 |
| IL-8 | 13,5 (4,3 - 2599,9) | 16 (4,3 – 2793,3) | P=0.177 |
| VEGF | 46,3 (2,6 - 681,6) | 57,7 (7,9 – 798,4) | P=0.262 |
| 4-1BB | 48,1 (0,1 - 344,2) | 46,7 (0,3 – 59,5) | P=0.455 |
| CXCL13 | 72,7 (20,2 - 705,7) | 74,9 (16,6 – 800,4) | P=0.803 |
| BAFF | 1159,2 (346,7 - 9788,4) | 1356,6 (342,5 – 10555,7) | P=0.004 |
Conclusions
Patients demonstrated a gradual enrichment of IL-6 and BAFF the number of prior lines of systemic therapy: patients more heavily pretreated presented higher baseline levels of those two cytokines. Our findings highlight the potential of baseline cytokine levels as a prognostic tool for metastatic clear cell renal cell carcinoma.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
BMS.
Disclosure
All authors have declared no conflicts of interest.
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