PMID- 31289683 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 2049-9450 (Print) IS - 2049-9469 (Electronic) IS - 2049-9450 (Linking) VI - 11 IP - 1 DP - 2019 Jul TI - Early blood rise in auto-antibodies to nuclear and smooth muscle antigens is predictive of prolonged survival and autoimmunity in metastatic-non-small cell lung cancer patients treated with PD-1 immune-check point blockade by nivolumab. PG - 81-90 LID - 10.3892/mco.2019.1859 [doi] AB - Immune-checkpoint blockade by Nivolumab, a human monoclonal antibody to programmed cell death receptor-1, is an emerging treatment for metastatic non-small cell lung cancer (mNSCLC). In order to prolong patient survival, this treatment requires a continuous cross-priming of tumor derived-antigens to supply fresh tumor-specific immune-effectors; a phenomenon that may also trigger auto-immune-related adverse events (irAEs). The present study therefore investigated the prognostic value of multiple autoimmunity-associated parameters in patients with mNSCLC who were undergoing Nivolumab treatment. This retrospective study included 92 mNSCLC patients who received salvage therapy with Nivolumab (3 mg/kg, biweekly) between September 2015 and June 2018. Log-rank test, Mantel-Cox and McPherson analyses were conducted to correlate patient progression-free survival (PFS) and overall survival (OS) with different parameters including blood cell counts, serum inflammatory markers and auto-antibodies (AAbs). A median PFS and OS of 10 [inter-quartile range (IQR): 5.8-14.2] and 16 [IQR: 6.2-25.8] months, respectively, were recorded, which did not correlated with age, histology or the number of previous chemotherapy lines. Male gender, the type of therapeutic regimens received prior to Nivolumab, and the occurrence of irAEs were revealed to be positive predictors of prolonged survival (P<0.05). Early detection (within 30 days) of >1AAbs among anti-nuclear antigens (ANAs), extractable nuclear antigens (ENAs) and anti-smooth cell antigens (ASMAs) correlated with prolonged PFS [hazard ratio (HR)=0.23; 95% confidence interval (CI): 0.08-0.62; P=0.004] and OS [HR=0.28 (95% CI: 0.09-0.88), P=0.03], with the type of treatment received prior to nivolumab (P=0.007) and with the risk of irAEs (P=0.002). In conclusion, increased serum levels of ANA, ENA and/or ASMA are consequential to Nivolumab administration and are predictive of a positive outcome in mNSCLC patients. FAU - Giannicola, Rocco AU - Giannicola R AD - Medical Oncology Unit, 'Bianchi-Melacrino-Morelli' Grand Metropolitan Hospital, I-89124 Reggio di Calabria, Italy. FAU - D'Arrigo, Graziella AU - D'Arrigo G AD - Statistical Unit, National Council of Research (CNR), Grand Metropolitan Hospital-IFC, I-89124 Reggio di Calabria, Italy. FAU - Botta, Cirino AU - Botta C AD - Medical Oncology Unit, Department of Experimental and Clinical Medicine, Magna Graecia University, I-88100 Catanzaro, Italy. FAU - Agostino, Rita AU - Agostino R AD - Medical Oncology Unit, 'Bianchi-Melacrino-Morelli' Grand Metropolitan Hospital, I-89124 Reggio di Calabria, Italy. FAU - Del Medico, Pietro AU - Del Medico P AD - Medical Oncology Unit, 'Bianchi-Melacrino-Morelli' Grand Metropolitan Hospital, I-89124 Reggio di Calabria, Italy. FAU - Falzea, Antonia Consuelo AU - Falzea AC AD - Medical Oncology Unit, 'Bianchi-Melacrino-Morelli' Grand Metropolitan Hospital, I-89124 Reggio di Calabria, Italy. FAU - Barbieri, Vito AU - Barbieri V AD - Medical Oncology Unit, Department of Experimental and Clinical Medicine, Magna Graecia University, I-88100 Catanzaro, Italy. FAU - Staropoli, Nicoletta AU - Staropoli N AD - Medical Oncology Unit, Department of Experimental and Clinical Medicine, Magna Graecia University, I-88100 Catanzaro, Italy. FAU - Del Giudice, Teresa AU - Del Giudice T AD - Medical Oncology Unit, Department of Experimental and Clinical Medicine, Magna Graecia University, I-88100 Catanzaro, Italy. FAU - Pastina, Pierpaolo AU - Pastina P AD - Radiation Oncology Unit, Siena University Hospital, I-53100 Siena, Italy. FAU - Nardone, Valerio AU - Nardone V AD - Radiation Oncology Unit, Siena University Hospital, I-53100 Siena, Italy. FAU - Monoriti, Marika AU - Monoriti M AD - Autoimmunity Laboratory, 'Bianchi-Melacrino-Morelli' Grand Metropolitan Hospital, I-89124 Reggio di Calabria, Italy. FAU - Calabrese, Graziella AU - Calabrese G AD - Radiology Unit, 'Bianchi-Melacrino-Morelli' Grand Metropolitan Hospital, I-89124 Reggio di Calabria, Italy. FAU - Tripepi, Giovanni AU - Tripepi G AD - Statistical Unit, National Council of Research (CNR), Grand Metropolitan Hospital-IFC, I-89124 Reggio di Calabria, Italy. FAU - Pirtoli, Luigi AU - Pirtoli L AD - Radiation Oncology Unit, Siena University Hospital, I-53100 Siena, Italy. AD - Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA. FAU - Tassone, Pierfrancesco AU - Tassone P AD - Medical Oncology Unit, Department of Experimental and Clinical Medicine, Magna Graecia University, I-88100 Catanzaro, Italy. AD - Translational Oncology Unit, Department of Experimental and Clinical Medicine, Magna Graecia University, I-88100 Catanzaro, Italy. FAU - Tagliaferri, Pierosandro AU - Tagliaferri P AD - Medical Oncology Unit, Department of Experimental and Clinical Medicine, Magna Graecia University, I-88100 Catanzaro, Italy. AD - Translational Oncology Unit, Department of Experimental and Clinical Medicine, Magna Graecia University, I-88100 Catanzaro, Italy. FAU - Correale, Pierpaolo AU - Correale P AD - Medical Oncology Unit, 'Bianchi-Melacrino-Morelli' Grand Metropolitan Hospital, I-89124 Reggio di Calabria, Italy. LA - eng PT - Journal Article DEP - 20190516 PL - England TA - Mol Clin Oncol JT - Molecular and clinical oncology JID - 101613422 PMC - PMC6547881 OTO - NOTNLM OT - PD-1/PDL-1-blockade OT - auto-antibodies OT - irAEs OT - mNSCLC EDAT- 2019/07/11 06:00 MHDA- 2019/07/11 06:01 PMCR- 2019/05/16 CRDT- 2019/07/11 06:00 PHST- 2018/11/02 00:00 [received] PHST- 2019/04/10 00:00 [accepted] PHST- 2019/07/11 06:00 [entrez] PHST- 2019/07/11 06:00 [pubmed] PHST- 2019/07/11 06:01 [medline] PHST- 2019/05/16 00:00 [pmc-release] AID - MCO-0-0-1859 [pii] AID - 10.3892/mco.2019.1859 [doi] PST - ppublish SO - Mol Clin Oncol. 2019 Jul;11(1):81-90. doi: 10.3892/mco.2019.1859. Epub 2019 May 16.