The Pan-Immune-Inflammation Value in Patients with Metastatic Melanoma Receiving First-Line Therapy.
Journal
Targeted oncology
ISSN: 1776-260X
Titre abrégé: Target Oncol
Pays: France
ID NLM: 101270595
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
accepted:
16
05
2021
pubmed:
3
6
2021
medline:
19
1
2022
entrez:
2
6
2021
Statut:
ppublish
Résumé
Since a non-negligible fraction of patients with metastatic melanoma does not experience long-term disease control, even with immunotherapy and targeted therapy, new biomarkers for patient stratification and treatment tailoring are needed in this setting. We investigated the association of a novel immune-inflammatory blood-based biomarker, the Pan-Immune-Inflammation Value (PIV), with clinical outcomes of patients with metastatic melanoma receiving first-line therapy. We retrospectively included patients treated at the Fondazione IRCCS Istituto Nazionale dei Tumori of Milan and having an available baseline complete blood cell count (CBC). PIV was calculated as: [neutrophil count (10 A total of 228 patients were included: 119 (52%) had been treated with immunotherapy and 109 (48%) with targeted therapy. PIV was significantly higher in patients with ECOG PS ≥ 1, high disease burden, synchronous metastases, and elevated baseline LDH level. High baseline PIV was independently associated with poor overall survival (adjusted hazard ratio [HR]: 2.06; 95% confidence interval [CI]: 1.30-3.29; adjusted P = 0.002) and progression-free survival (adjusted HR 1.56; 95% CI 1.01-2.41; adjusted P = 0.044). High PIV was also associated with primary resistance to both immunotherapy (odds ratio [OR]: 3.98; 95% CI 1.45-12.32; P = 0.005) and targeted therapy (OR: 8.42; 95% CI 2.50-34.5; P < 0.001). PIV showed a promising discrimination ability in terms of AIC and c-index when compared with other CBC-based biomarkers. PIV may guide the treatment decision process and the development of novel first-line treatment strategies in melanoma, but warrants further study and validation.
Sections du résumé
BACKGROUND
Since a non-negligible fraction of patients with metastatic melanoma does not experience long-term disease control, even with immunotherapy and targeted therapy, new biomarkers for patient stratification and treatment tailoring are needed in this setting.
OBJECTIVE
We investigated the association of a novel immune-inflammatory blood-based biomarker, the Pan-Immune-Inflammation Value (PIV), with clinical outcomes of patients with metastatic melanoma receiving first-line therapy.
PATIENTS AND METHODS
We retrospectively included patients treated at the Fondazione IRCCS Istituto Nazionale dei Tumori of Milan and having an available baseline complete blood cell count (CBC). PIV was calculated as: [neutrophil count (10
RESULTS
A total of 228 patients were included: 119 (52%) had been treated with immunotherapy and 109 (48%) with targeted therapy. PIV was significantly higher in patients with ECOG PS ≥ 1, high disease burden, synchronous metastases, and elevated baseline LDH level. High baseline PIV was independently associated with poor overall survival (adjusted hazard ratio [HR]: 2.06; 95% confidence interval [CI]: 1.30-3.29; adjusted P = 0.002) and progression-free survival (adjusted HR 1.56; 95% CI 1.01-2.41; adjusted P = 0.044). High PIV was also associated with primary resistance to both immunotherapy (odds ratio [OR]: 3.98; 95% CI 1.45-12.32; P = 0.005) and targeted therapy (OR: 8.42; 95% CI 2.50-34.5; P < 0.001). PIV showed a promising discrimination ability in terms of AIC and c-index when compared with other CBC-based biomarkers.
CONCLUSIONS
PIV may guide the treatment decision process and the development of novel first-line treatment strategies in melanoma, but warrants further study and validation.
Identifiants
pubmed: 34076798
doi: 10.1007/s11523-021-00819-0
pii: 10.1007/s11523-021-00819-0
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
529-536Références
Michielin O, van Akkooi ACJ, Ascierto PA, Dummer R, Keilholz U, clinicalguidelines@esmo.org EGCEa. Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019;30(12):1884-901.
Robert C, Long GV, Brady B, Dutriaux C, Di Giacomo AM, Mortier L, et al. Five-year outcomes with nivolumab in patients with wild-type BRAF advanced melanoma. J Clin Oncol. 2020;38(33):3937–46.
doi: 10.1200/JCO.20.00995
Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Lao CD, et al. Five-year survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2019;381(16):1535–46.
doi: 10.1056/NEJMoa1910836
Long GV, Flaherty KT, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, et al. Dabrafenib plus trametinib versus dabrafenib monotherapy in patients with metastatic BRAF V600E/K-mutant melanoma: long-term survival and safety analysis of a phase 3 study. Ann Oncol. 2019;30(11):1848.
doi: 10.1093/annonc/mdz221
Ascierto PA, McArthur GA, Dréno B, Atkinson V, Liszkay G, Di Giacomo AM, et al. Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial. Lancet Oncol. 2016;17(9):1248–60.
doi: 10.1016/S1470-2045(16)30122-X
Bartlett EK, Karakousis GC. Current staging and prognostic factors in melanoma. Surg Oncol Clin N Am. 2015;24(2):215–27.
doi: 10.1016/j.soc.2014.12.001
Ilieva KM, Correa I, Josephs DH, Karagiannis P, Egbuniwe IU, Cafferkey MJ, et al. Effects of BRAF mutations and BRAF inhibition on immune responses to melanoma. Mol Cancer Ther. 2014;13(12):2769–83.
doi: 10.1158/1535-7163.MCT-14-0290
Soudja SM, Wehbe M, Mas A, Chasson L, de Tenbossche CP, Huijbers I, et al. Tumor-initiated inflammation overrides protective adaptive immunity in an induced melanoma model in mice. Cancer Res. 2010;70(9):3515–25.
doi: 10.1158/0008-5472.CAN-09-4354
Weide B, Martens A, Hassel JC, Berking C, Postow MA, Bisschop K, et al. Baseline biomarkers for outcome of melanoma patients treated with pembrolizumab. Clin Cancer Res. 2016;22(22):5487–96.
doi: 10.1158/1078-0432.CCR-16-0127
Gebhardt C, Sevko A, Jiang H, Lichtenberger R, Reith M, Tarnanidis K, et al. Myeloid cells and related chronic inflammatory factors as novel predictive markers in melanoma treatment with ipilimumab. Clin Cancer Res. 2015;21(24):5453–9.
doi: 10.1158/1078-0432.CCR-15-0676
Fucà G, Guarini V, Antoniotti C, Morano F, Moretto R, Corallo S, et al. The Pan-Immune-Inflammation Value is a new prognostic biomarker in metastatic colorectal cancer: results from a pooled-analysis of the Valentino and TRIBE first-line trials. Br J Cancer. 2020;123(3):403–9.
doi: 10.1038/s41416-020-0894-7
Corti F, Lonardi S, Intini R, Salati M, Fenocchio E, Belli C, et al. The Pan-Immune-Inflammation Value in microsatellite instability-high metastatic colorectal cancer patients treated with immune checkpoint inhibitors. Eur J Cancer. 2021;150:155–67.
doi: 10.1016/j.ejca.2021.03.043
Ligorio F, Fucà G, Zattarin E, Lobefaro R, Zambelli L, Leporati R, et al. The Pan-Immune-Inflammation-Value Predicts the Survival of Patients with Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Breast Cancer Treated with First-Line Taxane-Trastuzumab-Pertuzumab. Cancers. 2021;13(8).
Hölzel M, Tüting T. Inflammation-induced plasticity in melanoma therapy and metastasis. Trends Immunol. 2016;37(6):364–74.
doi: 10.1016/j.it.2016.03.009
Fucà G, Galli G, Poggi M, Lo Russo G, Proto C, Imbimbo M, et al. Modulation of peripheral blood immune cells by early use of steroids and its association with clinical outcomes in patients with metastatic non-small cell lung cancer treated with immune checkpoint inhibitors. ESMO Open. 2019;4(1):e000457.
doi: 10.1136/esmoopen-2018-000457
Schwartz LH, Litière S, de Vries E, Ford R, Gwyther S, Mandrekar S, et al. RECIST 1.1-Update and clarification: from the RECIST committee. Eur J Cancer. 2016;62:132–7.
doi: 10.1016/j.ejca.2016.03.081
Lausen B, Schumacher M. Maximally selected rank statistics. Biometrics. 1992;48(1):73–85.
doi: 10.2307/2532740
Cook NR. Quantifying the added value of new biomarkers: how and how not. Diagn Progn Res. 2018;2:14.
doi: 10.1186/s41512-018-0037-2
Ferrucci PF, Ascierto PA, Pigozzo J, Del Vecchio M, Maio M, Antonini Cappellini GC, et al. Baseline neutrophils and derived neutrophil-to-lymphocyte ratio: prognostic relevance in metastatic melanoma patients receiving ipilimumab. Ann Oncol. 2018;29(2):524.
doi: 10.1093/annonc/mdx059
Rosner S, Kwong E, Shoushtari AN, Friedman CF, Betof AS, Brady MS, et al. Peripheral blood clinical laboratory variables associated with outcomes following combination nivolumab and ipilimumab immunotherapy in melanoma. Cancer Med. 2018;7(3):690–7.
doi: 10.1002/cam4.1356
Teterycz P, Jagodzińska-Mucha P, Cybulska-Stopa B, Mariuk-Jarema A, Kozak K, Koseła-Paterczyk H, et al. High baseline neutrophil-to-lymphocyte ratio predicts worse outcome in patients with metastatic BRAF-positive melanoma treated with BRAF and MEK inhibitors. Melanoma Res. 2018;28(5):435–41.
doi: 10.1097/CMR.0000000000000461
Labelle M, Begum S, Hynes RO. Platelets guide the formation of early metastatic niches. Proc Natl Acad Sci USA. 2014;111(30):E3053–61.
doi: 10.1073/pnas.1411082111
Rachidi S, Kaur M, Lautenschlaeger T, Li Z. Platelet count correlates with stage and predicts survival in melanoma. Platelets. 2019;30(8):1042–6.
doi: 10.1080/09537104.2019.1572879
Zhang F, Gong W. Prognostic value of the platelet-to-lymphocyte ratio in patients with melanoma: a meta-analysis. Front Oncol. 2020;10:1116.
doi: 10.3389/fonc.2020.01116
Iacono D, Basile D, Gerratana L, Vitale MG, Pelizzari G, Cinausero M, et al. Prognostic role of disease extent and lymphocyte-monocyte ratio in advanced melanoma. Melanoma Res. 2019;29(5):510–5.
doi: 10.1097/CMR.0000000000000584
Failing JJ, Yan Y, Porrata LF, Markovic SN. Lymphocyte-to-monocyte ratio is associated with survival in pembrolizumab-treated metastatic melanoma patients. Melanoma Res. 2017;27(6):596–600.
doi: 10.1097/CMR.0000000000000404
Huber V, Vallacchi V, Fleming V, Hu X, Cova A, Dugo M, et al. Tumor-derived microRNAs induce myeloid suppressor cells and predict immunotherapy resistance in melanoma. J Clin Invest. 2018;128(12):5505–16.
doi: 10.1172/JCI98060
Bordon Y. Tumour immunology: Platelets - a new target in cancer immunotherapy? Nat Rev Immunol. 2017;17(6):348.
doi: 10.1038/nri.2017.61