TY - JOUR
T1 - The systemic inflammatory response identifies patients with adverse clinical outcome from immunotherapy in hepatocellular carcinoma
AU - Muhammed, Ambreen
AU - Fulgenzi, Claudia Angela Maria
AU - Dharmapuri, Sirish
AU - Pinter, Matthias
AU - Balcar, Lorenz
AU - Scheiner, Bernhard
AU - Marron, Thomas U.
AU - Jun, Tomi
AU - Saeed, Anwaar
AU - Hildebrand, Hannah
AU - Muzaffar, Mahvish
AU - Navaid, Musharraf
AU - Naqash, Abdul Rafeh
AU - Gampa, Anuhya
AU - Ozbek, Umut
AU - Lin, Junk Yi
AU - Perone, Ylenia
AU - Vincenzi, Bruno
AU - Silletta, Marianna
AU - Pillai, Anjana
AU - Wang, Yinghong
AU - Khan, Uqba
AU - Huang, Yi Hsiang
AU - Bettinger, Dominik
AU - Abugabal, Yehia I.
AU - Kaseb, Ahmed
AU - Pressiani, Tiziana
AU - Personeni, Nicola
AU - Rimassa, Lorenza
AU - Nishida, Naoshi
AU - Tommaso, Luca Di
AU - Kudo, Masatoshi
AU - Vogel, Arndt
AU - Mauri, Francesco A.
AU - Cortellini, Alessio
AU - Sharma, Rohini
AU - D’alessio, Antonio
AU - Ang, Celina
AU - Pinato, David J.
N1 - Funding Information:
Conflicts of Interest: L.R. received consulting fees from Amgen, ArQule, AstraZeneca, Basilea, Bayer, BMS, Celgene, Eisai, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Lilly, MSD, Nerviano Medical Sciences, Roche, Sanofi, and Servier, Zymeworks; lecture fees from AbbVie, Amgen, Bayer, Eisai, Gilead, Incyte, Ipsen, Lilly, Merck Serono, Roche, and Sanofi; travel expenses from Ipsen; and institutional research funding from Agios, ARMO BioSciences, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche and, Zymeworks. N.P. reports receiving consulting fees from Amgen, Merck Serono, and Servier; lectures fees from AbbVie, Gilead, Lilly, and Sanofi; travel expenses from Amgen and ArQule; and institutional research funding from Basilea, Merck Serono, and Servier. M.P. is an investigator for Bayer, BMS, Lilly, and Roche, he received speaker honoraria from Bayer, BMS, Eisai, and MSD, he is a consultant for Bayer, BMS, Ipsen, Eisai, Lilly, Roche, and MSD, and he received travel support from Bayer, BMS, and Roche. B.S. received travel support from AbbVie, Ipsen and Gilead. D.B. received consulting fees from Bayer Healthcare, Boston Scientific, and Shionogi. Lectures: Falk Foundation. A.C. received consulting fees from MSD, BMS, AstraZeneca, and Roche; speakers’ fee from AstraZeneca, MSD, Novartis, and Astellas. D.J.P. received lecture fees from ViiV Healthcare and Bayer Healthcare, and travel expenses from BMS and Bayer Healthcare; consulting fees for Mina Therapeutics, EISAI, Roche, and Astra Zeneca; and received research funding (to institution) from MSD and BMS. All remaining authors have declared no conflict of interest.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/1/1
Y1 - 2022/1/1
N2 - Systemic inflammation is a hallmark of cancer, and it has a pivotal role in hepatocellular carcinoma (HCC) development and progression. We conducted a retrospective study including 362 patients receiving immune check-point inhibitors (ICIs) across three continents, evaluating the influence of neutrophiles to lymphocytes ratio (NLR), platelets to lymphocytes ratio (PLR), and prognostic nutritional index (PNI) on overall (OS), progression free survival (PFS), and radiologic re-sponses. In our 362 patients treated with immunotherapy, median OS and PFS were 9 and 3.5 months, respectively. Amongst tested inflammatory biomarkers, patients with NLR ≥ 5 had shorter OS (7.7 vs. 17.6 months, p < 0.0001), PFS (2.1 vs. 3.8 months, p = 0.025), and lower objective response rate (ORR) (12% vs. 22%, p = 0.034); similarly, patients with PLR ≥ 300 reported shorter OS (6.4 vs. 16.5 months, p < 0.0001) and PFS (1.8 vs. 3.7 months, p = 0.0006). NLR emerged as independent prognostic factors for OS in univariate and multivariate analysis (HR 1.95, 95%CI 1.45–2.64, p < 0.001; HR 1.73, 95%CI 1.23–2.42, p = 0.002) and PLR remained an independent prognostic factor for both OS and PFS in multivariate analysis (HR 1.60, 95%CI 1.6–2.40, p = 0.020; HR 1.99, 95%CI 1.11–3.49, p = 0.021). Systemic inflammation measured by NLR and PLR is an independent negative prognostic factor in HCC patients undergoing ICI therapy. Further studies are required to understand the biological mechanisms underlying this association and to investigate the predictive significance of circulating inflammatory biomarkers in HCC patients treated with ICIs.
AB - Systemic inflammation is a hallmark of cancer, and it has a pivotal role in hepatocellular carcinoma (HCC) development and progression. We conducted a retrospective study including 362 patients receiving immune check-point inhibitors (ICIs) across three continents, evaluating the influence of neutrophiles to lymphocytes ratio (NLR), platelets to lymphocytes ratio (PLR), and prognostic nutritional index (PNI) on overall (OS), progression free survival (PFS), and radiologic re-sponses. In our 362 patients treated with immunotherapy, median OS and PFS were 9 and 3.5 months, respectively. Amongst tested inflammatory biomarkers, patients with NLR ≥ 5 had shorter OS (7.7 vs. 17.6 months, p < 0.0001), PFS (2.1 vs. 3.8 months, p = 0.025), and lower objective response rate (ORR) (12% vs. 22%, p = 0.034); similarly, patients with PLR ≥ 300 reported shorter OS (6.4 vs. 16.5 months, p < 0.0001) and PFS (1.8 vs. 3.7 months, p = 0.0006). NLR emerged as independent prognostic factors for OS in univariate and multivariate analysis (HR 1.95, 95%CI 1.45–2.64, p < 0.001; HR 1.73, 95%CI 1.23–2.42, p = 0.002) and PLR remained an independent prognostic factor for both OS and PFS in multivariate analysis (HR 1.60, 95%CI 1.6–2.40, p = 0.020; HR 1.99, 95%CI 1.11–3.49, p = 0.021). Systemic inflammation measured by NLR and PLR is an independent negative prognostic factor in HCC patients undergoing ICI therapy. Further studies are required to understand the biological mechanisms underlying this association and to investigate the predictive significance of circulating inflammatory biomarkers in HCC patients treated with ICIs.
KW - Hepatocellular carcinoma
KW - Inflammatory biomarkers
KW - Neutrophil-lymphocyte ratio
KW - Platelet-lymphocyte ratio
KW - Prognostic nutritional index
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U2 - 10.3390/cancers14010186
DO - 10.3390/cancers14010186
M3 - Article
C2 - 35008350
AN - SCOPUS:85122032421
SN - 2072-6694
VL - 14
JO - Cancers
JF - Cancers
IS - 1
M1 - 186
ER -