Inflammatory indices and clinical factors in metastatic renal cell carcinoma patients treated with nivolumab: the development of a novel prognostic score (Meet-URO 15 study)

Abstract

Background: Despite the survival advantage, not all metastatic renal cell carcinoma (mRCC) patients achieve a long-term benefit from immunotherapy. Moreover, the identification of prognostic biomarkers is still an unmet clinical need. Methods: This multicenter retrospective study investigated the prognostic role of peripheral-blood inflammatory indices and clinical factors to develop a novel prognostic score in mRCC patients receiving at least second-line nivolumab. The complete blood count before the first cycle of therapy was assessed by calculating neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), and systemic inflammation response index (SIRI). Clinical factors included pre-treatment International Metastatic RCC Database Consortium (IMDC) score, line of therapy, and metastatic sites. Results: From October 2015 to November 2019, 571 mRCC patients received nivolumab as second- and further-line treatment in 69% and 31% of cases. In univariable and multivariable analyses all inflammatory indices, IMDC score, and bone metastases significantly correlated with overall survival (OS). The multivariable model with NLR, IMDC score, and bone metastases had the highest c-index (0.697) and was chosen for the developing of the score (Schneeweiss scoring system). After internal validation (bootstrap re-sampling), the final index (Meet-URO score) composed by NLR, IMDC score, and bone metastases had a c-index of 0.691. It identified five categories with distinctive OSs: group 1 (median OS – mOS = not reached), group 2 (mOS = 43.9 months), group 3 (mOS = 22.4 months), group 4 (mOS = 10.3 months), and group 5 (mOS = 3.2 months). Moreover, the Meet-URO score allowed for a fine risk-stratification across all three IMDC groups. Conclusion: The Meet-URO score allowed for the accurate stratification of pretreated mRCC patients receiving nivolumab and is easily applicable for clinical practice at no additional cost. Future steps include its external validation, the assessment of its predictivity, and its application to first-line combinations.

Prognostic Value of Baseline Medications Plus Neutrophil-to-Lymphocyte Ratio in the Effectiveness of Nivolumab and Pembrolizumab in Patients With Advanced Non-Small-Cell Lung Cancer: A Retrospective Study

“…Interestingly, despite the difference in the treatment lines between the later-line and first-line treatments and the patients' ethnicity among Japanese and Western populations, the prognostic utility of baseline NLR has been reported to be consistent (20)(21)(22). The present study combined baseline medications with the routinely available NLR at baseline as a novel prognostic score, and an NLR ≥ 3 was assigned 2 points as in previous studies (20)(21)(22). Rebuzzi et al (20) reported that in patients with metastatic renal cell carcinoma who received nivolumab (n = 571) as a second-and further-line setting, the Meet-URO prognostic score of baseline NLR and clinical factors showed a predictive ability for survival outcome.…”

“…Once validated, these parameters could be used in the clinical setting, as they are easily available and do not require additional costs or setup. Hence, NLR was selected for the development of the prognostic score, based on Rebuzzi et al (20).…”

“…Several studies have evaluated the association between baseline medications and the clinical outcomes of ICI treatment (16)(17)(18)(19). Additionally, several studies have reported the prognostic utility of baseline peripheral blood counts, such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-tolymphocyte ratio (20)(21)(22). Importantly, the impact of baseline medications and that of routinely available blood cell counts at baseline were evaluated separately in these studies.…”

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“…In the present study, Harrell's concordance statistic was similar to that reported by Buti et al (16). Interestingly, despite the difference in the treatment lines between the later-line and first-line treatments and the patients' ethnicity among Japanese and Western populations, the prognostic utility of baseline NLR has been reported to be consistent (20)(21)(22). The present study combined baseline medications with the routinely available NLR at baseline as a novel prognostic score, and an NLR ≥ 3 was assigned 2 points as in previous studies (20)(21)(22).…”

Prognostic and Predictive Factors in Advanced Urothelial Carcinoma Treated with Immune Checkpoint Inhibitors: A Review of the Current Evidence

“…Inflammatory indices from peripheral blood have been investigated in combination with other clinical prognostic factors within prognostic models for risk-stratification in several cancer types treated with ICIs, especially the NSCLC [ 91 , 98 , 99 , 100 ]. The interest in prognostic models has also recently been increasing for genitourinary tumours, including RCC [ 101 , 102 , 103 ] and UC [ 63 , 65 , 68 , 95 , 96 , 97 , 104 ].…”