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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Positive results from recent clinical trials led to the approval of immunotherapy based on checkpoint inhibitors &#40;ICI&#41; for a variety of cancers&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">1</span></a> The ICI-class drugs include anti-PD-1 &#40;nivolumab&#44; pembrolizumab&#41;&#44; anti-PD-L1 &#40;atezolizumab&#44; durvalumab&#44; avelumab&#41;&#44; and anti-cytotoxic T lymphocyte-associated antigen &#40;CTLA-4&#41; agents &#40;ipilimumab&#44; tremelimumab&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">2</span></a> It is important to mention that all trials leading to the approval of CTLA-4 or PD-1&#47;PD-L1 blocking agents excluded patients with pre-existing active autoimmune disorders &#40;AD&#41; from enrolment&#44;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">1</span></a> because of the potential for increased severe toxicity&#44; such as fulminant myocarditis&#46; Having an overactive immune system is the main reason why many patients with cancer and AD have not been included in hundreds of clinical trials of immunotherapy drugs&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Up to 80&#37; of patients under ICI experience inflammatory and immunorelated adverse events &#40;irAEs&#41; in various organs that can be detrimental to patient outcomes&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">3</span></a> The actual mechanism of ICI-induced toxicities remains poorly defined&#44; as does the exact mechanism of several AD&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">AD represent a spectrum of conditions with a common denominator&#58; the &#40;auto&#41; immune attack and damage of normal tissues&#44; either localized in individual organs&#44; systems&#44; or widespread &#40;systemic&#41;&#46; More than 80 distinct AD have been identified&#44; including some diseases with moderately high prevalence such as rheumatoid arthritis&#44; and inflammatory bowel disease&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">1</span></a> As the use of ICI expands to more types of cancer&#44; the need to determine the risk-benefit ratio in patients with cancer and pre-existing AD is increasing&#46; The number of studies and clinical cases reported is growing&#46; Khan et al&#46; conducted a study in the University of Texas in order to calculate the incidence of AD in the population of lung cancer patients older than 65&#46; Approximately 14&#37; to 25&#37; of the enrolled patients had an AD&#46; The most common AD diseases in the patients studied were rheumatoid arthritis &#40;5&#46;9&#37;&#41;&#44; psoriasis &#40;2&#46;8&#37;&#41;&#44; and polymyalgia rheumatic &#40;1&#46;8&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">4</span></a> A more recent paper by Khozin et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">5</span></a> also presents a high value of prevalence of AD in lung cancer patients &#40;22&#37;&#41;&#46; Potential explanations included in these articles&#44; for the relatively high rate of AD among patients with lung cancer include advanced age at diagnosis and smoking history&#44; which has been linked to higher risk of certain AD&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In this context&#44; the authors describe two clinical cases of patients with AD&#44; who were treated with immunotherapy&#44; without adverse effects&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Case 1</span><p id="par0025" class="elsevierStylePara elsevierViewall">The authors present the case of a 68-year-old male with a diagnosis of squamous cell carcinoma&#44; initially in stage IIIC &#40;T4N3M0&#41;&#46; He had a history of asymptomatic systemic lupus erythematosus&#44; diagnosed at the age of 48&#46; At the time of the lung cancer diagnosis&#44; he was being treated with hydroxychloroquine and corticosteroids for dyslipidaemia&#44; COPD and high blood pressure&#46; The patient was treated with first-line platinum and gemcitabine doublet&#44; after decision in a multidisciplinary meeting&#44; because of the large size of the tumour&#46; Docetaxel was used as second line therapy&#44; after evidence of imagiological progression&#44; and because of the PD-L1 negative expression on tumour cells&#44; Nivolumab was started after disease progression&#46; After four months of immunotherapy&#44; without adverse effects or flare of lupus&#44; imagological confirmation of the progression led to the suspension of therapy&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Case 2</span><p id="par0030" class="elsevierStylePara elsevierViewall">A 63-year-old male with a diagnosis of squamous cell carcinoma&#44; initially tumour stage IVA &#40;T2bN3M1a&#41;&#44; due to pleural&#44; pulmonary and ganglionic contralateral mediastinal metastasis is described&#46; The patient had history of psoriasis since he was 50 years old&#44; and smoking habits&#46; At the time of the lung cancer diagnosis&#44; his AD was stable only on topical corticotherapy&#46; The patient was treated with first-line platinum and gemcitabine doublet and&#44; after disease progression&#44; because of the PD-L1 negative expression on tumour cells&#44; Nivolumab was started as second line therapy&#46; The patient is currently in the 6th month of immunotherapy&#44; with stability of the imagological findings&#46; During the entire course of treatment with nivolumab&#44; his psoriasis remained stable without the need for systemic immunosuppression&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Several published articles have described the use of ICI in patients with AD&#44; similar to the cases reported in this article&#46; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41; In a group of 52 patients with pre-existing AD and advanced melanoma&#44; treated with PD-1 antibodies &#40;either pembrolizumab or nivolumab&#41;&#44; twenty &#40;38&#37;&#41; patients flared after a median of 1&#46;3 months after the initiation of PD-1 antibody treatment&#44; including 7&#47;13 with rheumatoid arthritis&#44; 3&#47;3 with polymyalgia rheumatica&#44; 2&#47;2 with Sjogren&#39;s syndrome&#44; 1&#47;2 with scleroderma&#44; 2&#47;2 with immune thrombocytopenic purpura&#44; 3&#47;8 with psoriasis&#44; and 1&#47;4 with Graves&#8217; disease&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">1</span></a> Khunger et al&#46;&#44; reported two cases of patients with Psoriasis&#44; who were treated with Nivolumab for up to 6 months&#44; without worsening of the underlying condition&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Leonardi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">6</span></a> also conducted a study in 56 patients with NSCLC and AD who received a PD-L1 inhibitor&#46; A total of 55&#37; of patients developed an AD flare and&#47;or an irAE&#46; Exacerbation of the AD occurred in 13 patients&#46; Immune-related adverse events occurred in 21 patients &#40;38&#37;&#41;&#46; PD-L1 therapy was permanently discontinued in eight patients because of irAEs&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Kennedy et al&#46; summarized the 8 largest retrospective case series that specifically evaluated patients with pre-existing autoimmunity who underwent treatment with ICIs&#46; The patients in these case series had a wide variety of well-controlled AD&#44; making it difficult to draw conclusions about safety regarding a specific disorder&#46; irAEs and autoimmune exacerbations occurred in a minority of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">2</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Based on the limited safety data from the published case series&#44; recommendations regarding which patients may be appropriate for considering ICI therapy in the setting of pre-existing AD were made&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">7</span></a> Patients with neurologic AD&#44; such as myasthenia gravis&#44; or life-threatening AD should not be considered candidates for ICI therapy&#46; Patients receiving high levels of immunosuppression should also be approached with caution&#46; Patients with pre-existing AD who could be considered for ICI treatment include those with a non-life-threatening AD&#44; who have good control on either no immunosuppression or relatively low levels of immunosuppressive therapy&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">It is recommended that a multidisciplinary team should be involved in the decision to initiate ICI therapy&#44; with close monitoring and clear consideration of the severity of the underlying autoimmunity&#44; prognosis of cancer&#44; alternative therapeutic options&#44; and a clear understanding of patients&#8217; preferences with respect to the risks and benefits of the various options&#46; Finally&#44; it is important to continue to expand understanding of the pathogenesis of irAEs and improve the ability to predict and manage irAEs&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not stated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leonardi et al<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NSCLC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PD-1&#47;PD-L1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38&#37;Gr 3&#47;4 10&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Menzies et al<span class="elsevierStyleSup">3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melanoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PD-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&#37;Gr 3&#47;4 10&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Danlos et al<span class="elsevierStyleSup">4</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melanoma &#40;80&#37;&#41;NSCLC &#40;13&#37;&#41;Other 7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PD-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Johnson et al<span class="elsevierStyleSup">5</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melanoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PD-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#37;Gr 3&#8211;5 31&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not stated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gutzmer et al<span class="elsevierStyleSup">6</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melanoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PD-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">42&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Richter et al<span class="elsevierStyleSup">7</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MelanomaNSCLCNHL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PD-1 &#40;69&#37;&#41;Ipilimumab 31&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38&#37;Gr 3&#47;4 25&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lee et al<span class="elsevierStyleSup">8</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melanoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ipilimumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&#37;Gr 3&#47;4 50&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Includes patients study with preexisting autoimmune disease&#46;</p>"
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            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Excludes immunotherapy-related events that were felt to be an exacerbation of the patient&#39;s underlying autoimmune disorder&#46;</p> <p class="elsevierStyleNotepara" id="npar0015">1 &#8211; Tison A&#44; Quere G&#44; Misery L&#44; et al&#46; OP0196 safety and efficacy of imune checkpoint inhibitors in patients with cancer and preexisting autoimmune diseases&#58; a nationwide multicenter retrospective study &#91;abstract&#93;&#46; Ann Rheum Dis 2018&#59;77&#58;Abstract 147&#46;</p> <p class="elsevierStyleNotepara" id="npar0020">2 &#8211; Leonardi GC&#44; Gainor JF&#44; Altan M&#44; et al&#46; Safety of programmed death-1 pathway inhibitors among patients with non-small-cell lung cancer and preexisting autoimmune disorders&#46; J Clin Oncol 2018&#59;36&#58;1905&#8211;1912&#46;</p> <p class="elsevierStyleNotepara" id="npar0025">3 &#8211; Menzies AM&#44; Johnson DB&#44; Ramanujam S&#44; et al&#46; Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab&#46; Ann Oncol 2017&#59;28&#58;368&#8211;376&#46;</p> <p class="elsevierStyleNotepara" id="npar0030">4 &#8211; Danlos FX&#44; Voisin AL&#44; Dyevre V&#44; et al&#46; Safety and efficacy of antiprogrammed death 1 antibodies in patients with cancer and pre-existing autoimmune or inflammatory disease&#46; Eur J Cancer 2018&#59;91&#58;21&#8211;29&#46;</p> <p class="elsevierStyleNotepara" id="npar0035">5 &#8211; Johnson DB&#44; Sullivan RJ&#44; Ott PA&#44; et al&#46; Ipilimumab therapy in patients with advanced melanoma and preexisting autoimmune disorders&#46; JAMA Oncol 2016&#59;2&#58;234&#8211;240&#46;</p> <p class="elsevierStyleNotepara" id="npar0040">6 &#8211; Gutzmer R&#44; Koop A&#44; Meier F&#44; et al&#46; Programmed cell death protein-1 &#40;PD-1&#41; inhibitor therapy in patients with advanced melanoma and preexisting autoimmunity or ipilimumab-triggered autoimmunity&#46; Eur J Cancer 2017&#59;75&#58;24&#8211;32&#46;</p> <p class="elsevierStyleNotepara" id="npar0045">7 &#8211; Richter MD&#44; Pinkston O&#44; Kottschade LA&#44; et al&#46; Brief report&#58; cancer immunotherapy in patients with preexisting rheumatic disease&#58; the Mayo Clinic experience&#46; Arthritis Rheumatol 2018&#59;70&#58;356&#8211;360&#46;</p> <p class="elsevierStyleNotepara" id="npar0050">8 &#8211; Lee B&#44; Wong A&#44; Kee D&#44; et al&#46; The use of ipilimumab in patients with rheumatoid arthritis and metastatic melanoma&#46; Ann Oncol 2016&#59;27&#58; 1174&#8211;1177&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Some retrospective case series evaluating patients with AD and ICI use&#46; Adapted from Laura et al&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:7 [
            0 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cancer immunotherapy in patients with preexisting autoimmune disorders"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "M&#46; Donia"
                            1 => "M&#46; Pedersen"
                            2 => "M&#46;I&#46; Svane"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00281-016-0595-8"
                      "Revista" => array:5 [
                        "tituloSerie" => "Semin Immunopathol"
                        "fecha" => "2017"
                        "volumen" => "39"
                        "paginaInicial" => "333"
                        "paginaFinal" => "337"
                      ]
                    ]
                  ]
                ]
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            1 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Preexisting autoimmune disease&#58; implications for immune checkpoint inhibitor therapy in solid tumors"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "L&#46;C&#46; Kennedy"
                            1 => "S&#46; Bhatia"
                            2 => "J&#46;A&#46; Thompson"
                            3 => "P&#46; Grivas"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "JNCCN"
                        "fecha" => "2019"
                        "volumen" => "17"
                      ]
                    ]
                  ]
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              ]
            ]
            2 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Use of immune checkpoint inhibitors in the treatment of patients with cancer and preexisting autoimmune disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "N&#46; Abdel-Wahab"
                            1 => "M&#46; Shah"
                            2 => "M&#46;A&#46; Lopez-Olivo"
                            3 => "M&#46;E&#46; Suarez-Almazor"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.7326/M17-2073"
                      "Revista" => array:2 [
                        "tituloSerie" => "Ann Int Med"
                        "fecha" => "2018"
                      ]
                    ]
                  ]
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              ]
            ]
            3 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prevalence of autoimmune disease among patients with lung cancer&#58; implications for immunotherapy treatment options"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "S&#46;A&#46; Khan"
                            1 => "S&#46;L&#46; Pruitt"
                            2 => "L&#46; Xuan"
                            3 => "D&#46;E&#46; Gerber"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jamaoncol.2015.5778"
                      "Revista" => array:4 [
                        "tituloSerie" => "JAMA Oncol"
                        "fecha" => "2016"
                        "volumen" => "2"
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Letter to the Editor
Are patients with autoimmune disorders eligible for immunotherapy?
D. Madama*, A. Pego
Pulmonology Department, University Hospital of Coimbra, Coimbra, Portugal
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Positive results from recent clinical trials led to the approval of immunotherapy based on checkpoint inhibitors &#40;ICI&#41; for a variety of cancers&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">1</span></a> The ICI-class drugs include anti-PD-1 &#40;nivolumab&#44; pembrolizumab&#41;&#44; anti-PD-L1 &#40;atezolizumab&#44; durvalumab&#44; avelumab&#41;&#44; and anti-cytotoxic T lymphocyte-associated antigen &#40;CTLA-4&#41; agents &#40;ipilimumab&#44; tremelimumab&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">2</span></a> It is important to mention that all trials leading to the approval of CTLA-4 or PD-1&#47;PD-L1 blocking agents excluded patients with pre-existing active autoimmune disorders &#40;AD&#41; from enrolment&#44;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">1</span></a> because of the potential for increased severe toxicity&#44; such as fulminant myocarditis&#46; Having an overactive immune system is the main reason why many patients with cancer and AD have not been included in hundreds of clinical trials of immunotherapy drugs&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Up to 80&#37; of patients under ICI experience inflammatory and immunorelated adverse events &#40;irAEs&#41; in various organs that can be detrimental to patient outcomes&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">3</span></a> The actual mechanism of ICI-induced toxicities remains poorly defined&#44; as does the exact mechanism of several AD&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">AD represent a spectrum of conditions with a common denominator&#58; the &#40;auto&#41; immune attack and damage of normal tissues&#44; either localized in individual organs&#44; systems&#44; or widespread &#40;systemic&#41;&#46; More than 80 distinct AD have been identified&#44; including some diseases with moderately high prevalence such as rheumatoid arthritis&#44; and inflammatory bowel disease&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">1</span></a> As the use of ICI expands to more types of cancer&#44; the need to determine the risk-benefit ratio in patients with cancer and pre-existing AD is increasing&#46; The number of studies and clinical cases reported is growing&#46; Khan et al&#46; conducted a study in the University of Texas in order to calculate the incidence of AD in the population of lung cancer patients older than 65&#46; Approximately 14&#37; to 25&#37; of the enrolled patients had an AD&#46; The most common AD diseases in the patients studied were rheumatoid arthritis &#40;5&#46;9&#37;&#41;&#44; psoriasis &#40;2&#46;8&#37;&#41;&#44; and polymyalgia rheumatic &#40;1&#46;8&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">4</span></a> A more recent paper by Khozin et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">5</span></a> also presents a high value of prevalence of AD in lung cancer patients &#40;22&#37;&#41;&#46; Potential explanations included in these articles&#44; for the relatively high rate of AD among patients with lung cancer include advanced age at diagnosis and smoking history&#44; which has been linked to higher risk of certain AD&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In this context&#44; the authors describe two clinical cases of patients with AD&#44; who were treated with immunotherapy&#44; without adverse effects&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Case 1</span><p id="par0025" class="elsevierStylePara elsevierViewall">The authors present the case of a 68-year-old male with a diagnosis of squamous cell carcinoma&#44; initially in stage IIIC &#40;T4N3M0&#41;&#46; He had a history of asymptomatic systemic lupus erythematosus&#44; diagnosed at the age of 48&#46; At the time of the lung cancer diagnosis&#44; he was being treated with hydroxychloroquine and corticosteroids for dyslipidaemia&#44; COPD and high blood pressure&#46; The patient was treated with first-line platinum and gemcitabine doublet&#44; after decision in a multidisciplinary meeting&#44; because of the large size of the tumour&#46; Docetaxel was used as second line therapy&#44; after evidence of imagiological progression&#44; and because of the PD-L1 negative expression on tumour cells&#44; Nivolumab was started after disease progression&#46; After four months of immunotherapy&#44; without adverse effects or flare of lupus&#44; imagological confirmation of the progression led to the suspension of therapy&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Case 2</span><p id="par0030" class="elsevierStylePara elsevierViewall">A 63-year-old male with a diagnosis of squamous cell carcinoma&#44; initially tumour stage IVA &#40;T2bN3M1a&#41;&#44; due to pleural&#44; pulmonary and ganglionic contralateral mediastinal metastasis is described&#46; The patient had history of psoriasis since he was 50 years old&#44; and smoking habits&#46; At the time of the lung cancer diagnosis&#44; his AD was stable only on topical corticotherapy&#46; The patient was treated with first-line platinum and gemcitabine doublet and&#44; after disease progression&#44; because of the PD-L1 negative expression on tumour cells&#44; Nivolumab was started as second line therapy&#46; The patient is currently in the 6th month of immunotherapy&#44; with stability of the imagological findings&#46; During the entire course of treatment with nivolumab&#44; his psoriasis remained stable without the need for systemic immunosuppression&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Several published articles have described the use of ICI in patients with AD&#44; similar to the cases reported in this article&#46; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41; In a group of 52 patients with pre-existing AD and advanced melanoma&#44; treated with PD-1 antibodies &#40;either pembrolizumab or nivolumab&#41;&#44; twenty &#40;38&#37;&#41; patients flared after a median of 1&#46;3 months after the initiation of PD-1 antibody treatment&#44; including 7&#47;13 with rheumatoid arthritis&#44; 3&#47;3 with polymyalgia rheumatica&#44; 2&#47;2 with Sjogren&#39;s syndrome&#44; 1&#47;2 with scleroderma&#44; 2&#47;2 with immune thrombocytopenic purpura&#44; 3&#47;8 with psoriasis&#44; and 1&#47;4 with Graves&#8217; disease&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">1</span></a> Khunger et al&#46;&#44; reported two cases of patients with Psoriasis&#44; who were treated with Nivolumab for up to 6 months&#44; without worsening of the underlying condition&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Leonardi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">6</span></a> also conducted a study in 56 patients with NSCLC and AD who received a PD-L1 inhibitor&#46; A total of 55&#37; of patients developed an AD flare and&#47;or an irAE&#46; Exacerbation of the AD occurred in 13 patients&#46; Immune-related adverse events occurred in 21 patients &#40;38&#37;&#41;&#46; PD-L1 therapy was permanently discontinued in eight patients because of irAEs&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Kennedy et al&#46; summarized the 8 largest retrospective case series that specifically evaluated patients with pre-existing autoimmunity who underwent treatment with ICIs&#46; The patients in these case series had a wide variety of well-controlled AD&#44; making it difficult to draw conclusions about safety regarding a specific disorder&#46; irAEs and autoimmune exacerbations occurred in a minority of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">2</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Based on the limited safety data from the published case series&#44; recommendations regarding which patients may be appropriate for considering ICI therapy in the setting of pre-existing AD were made&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">7</span></a> Patients with neurologic AD&#44; such as myasthenia gravis&#44; or life-threatening AD should not be considered candidates for ICI therapy&#46; Patients receiving high levels of immunosuppression should also be approached with caution&#46; Patients with pre-existing AD who could be considered for ICI treatment include those with a non-life-threatening AD&#44; who have good control on either no immunosuppression or relatively low levels of immunosuppressive therapy&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">It is recommended that a multidisciplinary team should be involved in the decision to initiate ICI therapy&#44; with close monitoring and clear consideration of the severity of the underlying autoimmunity&#44; prognosis of cancer&#44; alternative therapeutic options&#44; and a clear understanding of patients&#8217; preferences with respect to the risks and benefits of the various options&#46; Finally&#44; it is important to continue to expand understanding of the pathogenesis of irAEs and improve the ability to predict and manage irAEs&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Number<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tumour&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ICI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AD flare&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">irAE rates<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Discontinuation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tison et al<span class="elsevierStyleSup">1</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">112&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melanoma &#40;59&#37;&#41; NSCLC &#40;35&#37;&#41;Other &#40;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PD-1&#47;PD-L1 85&#37; of patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">42&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38&#37;Gr 3&#8211;5 16&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not stated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leonardi et al<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NSCLC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PD-1&#47;PD-L1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38&#37;Gr 3&#47;4 10&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Menzies et al<span class="elsevierStyleSup">3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melanoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PD-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&#37;Gr 3&#47;4 10&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Danlos et al<span class="elsevierStyleSup">4</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melanoma &#40;80&#37;&#41;NSCLC &#40;13&#37;&#41;Other 7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PD-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Johnson et al<span class="elsevierStyleSup">5</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melanoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PD-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#37;Gr 3&#8211;5 31&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not stated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gutzmer et al<span class="elsevierStyleSup">6</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melanoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PD-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">42&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Richter et al<span class="elsevierStyleSup">7</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MelanomaNSCLCNHL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PD-1 &#40;69&#37;&#41;Ipilimumab 31&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38&#37;Gr 3&#47;4 25&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lee et al<span class="elsevierStyleSup">8</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melanoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ipilimumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&#37;Gr 3&#47;4 50&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2586804.png"
              ]
            ]
          ]
          "notaPie" => array:2 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Includes patients study with preexisting autoimmune disease&#46;</p>"
            ]
            1 => array:3 [
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Excludes immunotherapy-related events that were felt to be an exacerbation of the patient&#39;s underlying autoimmune disorder&#46;</p> <p class="elsevierStyleNotepara" id="npar0015">1 &#8211; Tison A&#44; Quere G&#44; Misery L&#44; et al&#46; OP0196 safety and efficacy of imune checkpoint inhibitors in patients with cancer and preexisting autoimmune diseases&#58; a nationwide multicenter retrospective study &#91;abstract&#93;&#46; Ann Rheum Dis 2018&#59;77&#58;Abstract 147&#46;</p> <p class="elsevierStyleNotepara" id="npar0020">2 &#8211; Leonardi GC&#44; Gainor JF&#44; Altan M&#44; et al&#46; Safety of programmed death-1 pathway inhibitors among patients with non-small-cell lung cancer and preexisting autoimmune disorders&#46; J Clin Oncol 2018&#59;36&#58;1905&#8211;1912&#46;</p> <p class="elsevierStyleNotepara" id="npar0025">3 &#8211; Menzies AM&#44; Johnson DB&#44; Ramanujam S&#44; et al&#46; Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab&#46; Ann Oncol 2017&#59;28&#58;368&#8211;376&#46;</p> <p class="elsevierStyleNotepara" id="npar0030">4 &#8211; Danlos FX&#44; Voisin AL&#44; Dyevre V&#44; et al&#46; Safety and efficacy of antiprogrammed death 1 antibodies in patients with cancer and pre-existing autoimmune or inflammatory disease&#46; Eur J Cancer 2018&#59;91&#58;21&#8211;29&#46;</p> <p class="elsevierStyleNotepara" id="npar0035">5 &#8211; Johnson DB&#44; Sullivan RJ&#44; Ott PA&#44; et al&#46; Ipilimumab therapy in patients with advanced melanoma and preexisting autoimmune disorders&#46; JAMA Oncol 2016&#59;2&#58;234&#8211;240&#46;</p> <p class="elsevierStyleNotepara" id="npar0040">6 &#8211; Gutzmer R&#44; Koop A&#44; Meier F&#44; et al&#46; Programmed cell death protein-1 &#40;PD-1&#41; inhibitor therapy in patients with advanced melanoma and preexisting autoimmunity or ipilimumab-triggered autoimmunity&#46; Eur J Cancer 2017&#59;75&#58;24&#8211;32&#46;</p> <p class="elsevierStyleNotepara" id="npar0045">7 &#8211; Richter MD&#44; Pinkston O&#44; Kottschade LA&#44; et al&#46; Brief report&#58; cancer immunotherapy in patients with preexisting rheumatic disease&#58; the Mayo Clinic experience&#46; Arthritis Rheumatol 2018&#59;70&#58;356&#8211;360&#46;</p> <p class="elsevierStyleNotepara" id="npar0050">8 &#8211; Lee B&#44; Wong A&#44; Kee D&#44; et al&#46; The use of ipilimumab in patients with rheumatoid arthritis and metastatic melanoma&#46; Ann Oncol 2016&#59;27&#58; 1174&#8211;1177&#46;</p>"
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Article information
ISSN: 25310437
Original language: English
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