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Cancers 2019, 11(2), 223; https://doi.org/10.3390/cancers11020223

Combination of Baseline LDH, Performance Status and Age as Integrated Algorithm to Identify Solid Tumor Patients with Higher Probability of Response to Anti PD-1 and PD-L1 Monoclonal Antibodies

1
Medical Oncology Unit, Fondazione IRCCS, Istituto Nazionale dei Tumori di Milano, Via Giacomo Venezian 1, 20133 Milan, Italy
2
Bioinformatics and Biostatistics Unit, Fondazione IRCCS, Istituto Nazionale dei Tumori di Milano, Via Giacomo Venezian 1, 20133 Milan, Italy
3
IFOM (Fondazione Istituto FIRC di Oncologia Molecolare), via Adamello 16, 20139 Milan, Italy
4
Department of Oncology and Hemato-Oncology, Universita’ degli Studi di Milano, 20122 Milan, Italy
*
Author to whom correspondence should be addressed.
Received: 12 December 2018 / Revised: 19 January 2019 / Accepted: 12 February 2019 / Published: 14 February 2019
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Abstract

Predictive biomarkers of response to immune-checkpoint inhibitors (ICIs) are an urgent clinical need. The aim of this study is to identify manageable parameters to use in clinical practice to select patients with higher probability of response to ICIs. Two-hundred-and-seventy-one consecutive metastatic solid tumor patients, treated from 2013 until 2017 with anti- Programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) ICIs, were evaluated for baseline lactate dehydrogenase (LDH) serum level, performance status (PS), age, neutrophil-lymphocyte ratio, type of immunotherapy, number of metastatic sites, histology, and sex. A training and validation set were used to build and test models, respectively. The variables’ effects were assessed through odds ratio estimates (OR) and area under the receive operating characteristic curves (AUC), from univariate and multivariate logistic regression models. A final multivariate model with LDH, age and PS showed significant ORs and an AUC of 0.771. Results were statistically validated and used to devise an Excel algorithm to calculate the patient’s response probabilities. We implemented an interactive Excel algorithm based on three variables (baseline LDH serum level, age and PS) which is able to provide a higher performance in response prediction to ICIs compared with LDH alone. This tool could be used in a real-life setting to identify ICIs in responding patients. View Full-Text
Keywords: immune-checkpoint inhibitors; LDH; biomarkers immune-checkpoint inhibitors; LDH; biomarkers
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Cona, M.S.; Lecchi, M.; Cresta, S.; Damian, S.; Del Vecchio, M.; Necchi, A.; Poggi, M.M.; Raggi, D.; Randon, G.; Ratta, R.; Signorelli, D.; Vernieri, C.; de Braud, F.; Verderio, P.; Di Nicola, M. Combination of Baseline LDH, Performance Status and Age as Integrated Algorithm to Identify Solid Tumor Patients with Higher Probability of Response to Anti PD-1 and PD-L1 Monoclonal Antibodies. Cancers 2019, 11, 223.

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