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)

Sara Elena Rebuzzi; Alessio Signori; Giuseppe Luigi Banna; Marco Maruzzo; Ugo De Giorgi; Paolo Pedrazzoli; Andrea Sbrana; Paolo Andrea Zucali; Cristina Masini; Emanuele Naglieri; Giuseppe Procopio; Sara Merler; Laura Tomasello; Lucia Fratino; Cinzia Baldessari; Riccardo Ricotta; Stefano Panni; Veronica Mollica; Maria Sorarù; Matteo Santoni; Alessio Cortellini; Veronica Prati; Hector Josè Soto Parra; Marco Stellato; Francesco Atzori; Sandro Pignata; Carlo Messina; Marco Messina; Franco Morelli; Giuseppe Prati; Franco Nolè; Francesca Vignani; Alessia Cavo; Giandomenico Roviello; Francesco Pierantoni; Chiara Casadei; Melissa Bersanelli; Silvia Chiellino; Federico Paolieri; Matteo Perrino; Matteo Brunelli; Roberto Iacovelli; Camillo Porta; Sebastiano Buti; Giuseppe Fornarini

doi:10.1177/17588359211019642

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)

Sara Elena Rebuzzi, Alessio Signori, Giuseppe Luigi Banna, Marco Maruzzo, Ugo De Giorgi, Paolo Pedrazzoli, Andrea Sbrana, Paolo Andrea Zucali, Cristina Masini, Emanuele Naglieri, Giuseppe Procopio, Sara Merler, Laura Tomasello, Lucia Fratino, Cinzia Baldessari, Riccardo Ricotta, Stefano Panni, Veronica Mollica, Maria Sorarù, Matteo SantoniAlessio Cortellini, Veronica Prati, Hector Josè Soto Parra, Marco Stellato, Francesco Atzori, Sandro Pignata, Carlo Messina, Marco Messina, Franco Morelli, Giuseppe Prati, Franco Nolè, Francesca Vignani, Alessia Cavo, Giandomenico Roviello, Francesco Pierantoni, Chiara Casadei, Melissa Bersanelli, Silvia Chiellino, Federico Paolieri, Matteo Perrino, Matteo Brunelli, Roberto Iacovelli, Camillo Porta, Sebastiano Buti, Giuseppe Fornarini

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Journal	Therapeutic Advances in Medical Oncology
Volume	13
DOIs	https://doi.org/10.1177/17588359211019642
Publication status	Published - 2021

Keywords

biomarkers
clinical factors
immune checkpoint inhibitor
immunotherapy
prognostic score
renal cell carcinoma

ASJC Scopus subject areas

Oncology

Access to Document

10.1177/17588359211019642

Cite this

Rebuzzi, S. E., Signori, A., Banna, G. L., Maruzzo, M., De Giorgi, U., Pedrazzoli, P., Sbrana, A., Zucali, P. A., Masini, C., Naglieri, E., Procopio, G., Merler, S., Tomasello, L., Fratino, L., Baldessari, C., Ricotta, R., Panni, S., Mollica, V., Sorarù, M., ... Fornarini, G. (2021). 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). Therapeutic Advances in Medical Oncology, 13. https://doi.org/10.1177/17588359211019642

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). / Rebuzzi, Sara Elena; Signori, Alessio; Banna, Giuseppe Luigi et al.

In: Therapeutic Advances in Medical Oncology, Vol. 13, 2021.

Research output: Contribution to journal › Article › peer-review

Rebuzzi, SE, Signori, A, Banna, GL, Maruzzo, M , De Giorgi, U , Pedrazzoli, P, Sbrana, A, Zucali, PA , Masini, C , Naglieri, E , Procopio, G, Merler, S, Tomasello, L, Fratino, L, Baldessari, C, Ricotta, R, Panni, S, Mollica, V, Sorarù, M, Santoni, M, Cortellini, A, Prati, V, Soto Parra, HJ, Stellato, M, Atzori, F, Pignata, S, Messina, C, Messina, M, Morelli, F, Prati, G, Nolè, F, Vignani, F, Cavo, A, Roviello, G, Pierantoni, F, Casadei, C, Bersanelli, M, Chiellino, S, Paolieri, F, Perrino, M, Brunelli, M, Iacovelli, R, Porta, C, Buti, S & Fornarini, G 2021, '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)', Therapeutic Advances in Medical Oncology, vol. 13. https://doi.org/10.1177/17588359211019642

@article{e5fa753017384bb9938ea372560c9241,

title = "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.",

keywords = "biomarkers, clinical factors, immune checkpoint inhibitor, immunotherapy, prognostic score, renal cell carcinoma",

author = "Rebuzzi, {Sara Elena} and Alessio Signori and Banna, {Giuseppe Luigi} and Marco Maruzzo and {De Giorgi}, Ugo and Paolo Pedrazzoli and Andrea Sbrana and Zucali, {Paolo Andrea} and Cristina Masini and Emanuele Naglieri and Giuseppe Procopio and Sara Merler and Laura Tomasello and Lucia Fratino and Cinzia Baldessari and Riccardo Ricotta and Stefano Panni and Veronica Mollica and Maria Sorar{\`u} and Matteo Santoni and Alessio Cortellini and Veronica Prati and {Soto Parra}, {Hector Jos{\`e}} and Marco Stellato and Francesco Atzori and Sandro Pignata and Carlo Messina and Marco Messina and Franco Morelli and Giuseppe Prati and Franco Nol{\`e} and Francesca Vignani and Alessia Cavo and Giandomenico Roviello and Francesco Pierantoni and Chiara Casadei and Melissa Bersanelli and Silvia Chiellino and Federico Paolieri and Matteo Perrino and Matteo Brunelli and Roberto Iacovelli and Camillo Porta and Sebastiano Buti and Giuseppe Fornarini",

note = "Funding Information: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was funded by the Italian Ministry of Health (Ricerca Corrente 2018–2021 grants) that financially support their current research focused on the identification of prognostic and predictive markers for patients with genitourinary tumors. Funding Information: The authors wish to really thank Dr. Luca Carmisciano of the Department of Health Sciences (DISSAL), Section of Biostatistics of University of Genoa, for developing the web calculator of the Meet URO score. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was funded by the Italian Ministry of Health (Ricerca Corrente 2018?2021 grants) that financially support their current research focused on the identification of prognostic and predictive markers for patients with genitourinary tumors. Funding Information: Dr Fornarini services advisory boards for Astellas, Janssen, Pfizer, Bayer, MSD, and Merck, and received travel accommodation from Astellas, Janssen, and Bayer. Dr Buti received honoraria as a speaker at scientific events and in an advisory role by BMS, Pfizer; MSD, Ipsen, Roche, Eli Lilly, AstraZeneca, Pierre-Fabre, Novartis. Dr Banna reports personal fees from AstraZeneca, Janssen-Cilag, Boehringer Ingelheim, Roche, and non-financial support from Bristol-Myers Squibb, AstraZeneca, MedImmune, Pierre Fabre, IPSEN, outside the submitted work. Dr De Giorgi services as an advisory/board member of Astellas, Bayer, Bristol-Myers Squibb, IPSEN, Janssen, Merck, Pfizer, and Sanofi, received research grant/funding to the institution from AstraZeneca, Roche, Sanofi, and travel/accommodations/expenses from Bristol-Myers Squibb, IPSEN, Janssen, and Pfizer. Dr Zucali services advisory boards/consulting for Pfizer, Bristol-Myers Squibb, MSD, IPSEN, Novartis, Roche, Amgen, AstraZeneca, Sanofi, Janssen, and Astellas. Dr Masini received personal fees as a speaker from Astellas, as a consultant from IPSEN, MSD, and Janssen, and for travel accommodation from BMS, Pfizer, Astellas, Janssen, and IPSEN. Dr Procopio services advisory boards/consulting for Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Janssen, IPSEN, Merk, MSD, Novartis, and Pfizer. Dr Cortellini receives speaker fees/grant consultancies from Astrazeneca, BMS, MSD, Roche, Novartis, and Astellas. Dr Morelli received grants from MSD and Pfizer. Dr Bersanelli received research funding to the institution from Roche, Pfizer, Seqirus UK, AstraZeneca, Bristol-Myers Squibb, Novartis, and Sanofi, and received personal fees for advisory role, copyright transfer, consultancies, and as speaker at scientific events from Sciclone Pharmaceuticals, Bristol-Myers Squibb, AstraZeneca, Pierre-Fabre, Novartis, and Pfizer. The other authors have no conflicts of interest to disclose. Publisher Copyright: {\textcopyright} The Author(s), 2021.",

year = "2021",

doi = "10.1177/17588359211019642",

language = "English",

volume = "13",

journal = "Therapeutic Advances in Medical Oncology",

issn = "1758-8340",

publisher = "SAGE Publications Inc.",

}

TY - JOUR

T1 - Inflammatory indices and clinical factors in metastatic renal cell carcinoma patients treated with nivolumab

T2 - the development of a novel prognostic score (Meet-URO 15 study)

AU - Rebuzzi, Sara Elena

AU - Signori, Alessio

AU - Banna, Giuseppe Luigi

AU - Maruzzo, Marco

AU - De Giorgi, Ugo

AU - Pedrazzoli, Paolo

AU - Sbrana, Andrea

AU - Zucali, Paolo Andrea

AU - Masini, Cristina

AU - Naglieri, Emanuele

AU - Procopio, Giuseppe

AU - Merler, Sara

AU - Tomasello, Laura

AU - Fratino, Lucia

AU - Baldessari, Cinzia

AU - Ricotta, Riccardo

AU - Panni, Stefano

AU - Mollica, Veronica

AU - Sorarù, Maria

AU - Santoni, Matteo

AU - Cortellini, Alessio

AU - Prati, Veronica

AU - Soto Parra, Hector Josè

AU - Stellato, Marco

AU - Atzori, Francesco

AU - Pignata, Sandro

AU - Messina, Carlo

AU - Messina, Marco

AU - Morelli, Franco

AU - Prati, Giuseppe

AU - Nolè, Franco

AU - Vignani, Francesca

AU - Cavo, Alessia

AU - Roviello, Giandomenico

AU - Pierantoni, Francesco

AU - Casadei, Chiara

AU - Bersanelli, Melissa

AU - Chiellino, Silvia

AU - Paolieri, Federico

AU - Perrino, Matteo

AU - Brunelli, Matteo

AU - Iacovelli, Roberto

AU - Porta, Camillo

AU - Buti, Sebastiano

AU - Fornarini, Giuseppe

N1 - Funding Information: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was funded by the Italian Ministry of Health (Ricerca Corrente 2018–2021 grants) that financially support their current research focused on the identification of prognostic and predictive markers for patients with genitourinary tumors. Funding Information: The authors wish to really thank Dr. Luca Carmisciano of the Department of Health Sciences (DISSAL), Section of Biostatistics of University of Genoa, for developing the web calculator of the Meet URO score. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was funded by the Italian Ministry of Health (Ricerca Corrente 2018?2021 grants) that financially support their current research focused on the identification of prognostic and predictive markers for patients with genitourinary tumors. Funding Information: Dr Fornarini services advisory boards for Astellas, Janssen, Pfizer, Bayer, MSD, and Merck, and received travel accommodation from Astellas, Janssen, and Bayer. Dr Buti received honoraria as a speaker at scientific events and in an advisory role by BMS, Pfizer; MSD, Ipsen, Roche, Eli Lilly, AstraZeneca, Pierre-Fabre, Novartis. Dr Banna reports personal fees from AstraZeneca, Janssen-Cilag, Boehringer Ingelheim, Roche, and non-financial support from Bristol-Myers Squibb, AstraZeneca, MedImmune, Pierre Fabre, IPSEN, outside the submitted work. Dr De Giorgi services as an advisory/board member of Astellas, Bayer, Bristol-Myers Squibb, IPSEN, Janssen, Merck, Pfizer, and Sanofi, received research grant/funding to the institution from AstraZeneca, Roche, Sanofi, and travel/accommodations/expenses from Bristol-Myers Squibb, IPSEN, Janssen, and Pfizer. Dr Zucali services advisory boards/consulting for Pfizer, Bristol-Myers Squibb, MSD, IPSEN, Novartis, Roche, Amgen, AstraZeneca, Sanofi, Janssen, and Astellas. Dr Masini received personal fees as a speaker from Astellas, as a consultant from IPSEN, MSD, and Janssen, and for travel accommodation from BMS, Pfizer, Astellas, Janssen, and IPSEN. Dr Procopio services advisory boards/consulting for Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Janssen, IPSEN, Merk, MSD, Novartis, and Pfizer. Dr Cortellini receives speaker fees/grant consultancies from Astrazeneca, BMS, MSD, Roche, Novartis, and Astellas. Dr Morelli received grants from MSD and Pfizer. Dr Bersanelli received research funding to the institution from Roche, Pfizer, Seqirus UK, AstraZeneca, Bristol-Myers Squibb, Novartis, and Sanofi, and received personal fees for advisory role, copyright transfer, consultancies, and as speaker at scientific events from Sciclone Pharmaceuticals, Bristol-Myers Squibb, AstraZeneca, Pierre-Fabre, Novartis, and Pfizer. The other authors have no conflicts of interest to disclose. Publisher Copyright: © The Author(s), 2021.

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - biomarkers

KW - clinical factors

KW - immune checkpoint inhibitor

KW - immunotherapy

KW - prognostic score

KW - renal cell carcinoma

UR - http://www.scopus.com/inward/record.url?scp=85107317392&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85107317392&partnerID=8YFLogxK

U2 - 10.1177/17588359211019642

DO - 10.1177/17588359211019642

M3 - Article

AN - SCOPUS:85107317392

SN - 1758-8340

VL - 13

JO - Therapeutic Advances in Medical Oncology

JF - Therapeutic Advances in Medical Oncology

ER -

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

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this