EARLY inflammatory metabolic trajectories derived from routine blood markers predicted overall survival, progression free survival, and durable benefit in patients with metastatic renal cell carcinoma receiving nivolumab, according to findings from a multicentre real world cohort study.
The results suggest that combining commonly available laboratory markers into inflammatory metabolic trajectory phenotypes may improve early prognostic assessment during treatment.
Researchers evaluated 498 previously treated patients with metastatic renal cell carcinoma who received nivolumab monotherapy. A prespecified 28 day landmark framework was used to examine baseline and 1 month measurements of lactate dehydrogenase and complete blood count derived inflammatory indices. These included neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, and systemic immune inflammation index. Baseline values, 1 month values, and relative changes between the two time points were standardised before unsupervised clustering identified three inflammatory metabolic trajectory phenotypes among 329 eligible patients.
Inflammatory Metabolic Trajectories Differentiate Survival
The three phenotypes were classified as inflammatory metabolic quiescent, inflammatory metabolic quiescent to inflamed, and inflammatory metabolic inflamed persistent. Of the 329 phenotype eligible patients, 142 were assigned to the quiescent group, 69 to the quiescent to inflamed group, and 118 to the inflamed persistent group.
Survival outcomes differed significantly across the three inflammatory metabolic trajectory phenotypes for both overall survival and progression free survival. Compared with the inflammatory metabolic quiescent phenotype, the inflammatory metabolic inflamed persistent phenotype was associated with significantly poorer overall survival: (hazard ratio:1.63; 95% CI:1.09–2.45; p=0.019). It was also associated with worse progression free survival: (hazard ratio:1.92; 95% CI:1.36–2.73; p<0.001).
The inflammatory metabolic quiescent to inflamed phenotype did not demonstrate statistically significant differences in either overall survival: (hazard ratio:1.30; 95% CI:0.82–2.07; p=0.262) or progression free survival: (hazard ratio:1.21; 95% CI:0.82–1.79; p=0.336) compared with the quiescent phenotype.
Potential Role in Early Prognostic Assessment
Rates of 24 month overall survival also differed across the inflammatory metabolic trajectory phenotypes. After adjustment for relevant clinical variables, phenotype remained associated with the likelihood of surviving for at least 24 months, indicating that these early inflammatory metabolic patterns may provide additional prognostic information beyond established clinical characteristics.
The investigators concluded that inflammatory metabolic trajectory phenotypes generated from routinely available laboratory markers within the first month of treatment were clinically interpretable and associated with overall survival, progression free survival, and durable benefit in patients with metastatic renal cell carcinoma treated with nivolumab. They noted that external validation and prospective evaluation in contemporary immune checkpoint inhibitor based treatment regimens are needed before these findings can be applied more broadly in clinical practice.
Reference
Fiala O et al. Early systemic inflammatory–metabolic trajectory phenotypes are associated with survival outcomes in metastatic renal cell carcinoma treated with nivolumab. Sci Rep. 2026; https://doi.org/10.1038/s41598-026-60731-3.
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