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ana-related autoimmune diseases immune-related adverse events month download article/chapter t-cell checkpoint blockade small-cell lung cancer small-cell lung cancer immune-related thyroid dysfunction recurrent squamous-cell carcinoma pd-1/pd-l1 inhibitors pd-1/pd-l1 blockade advanced renal-cell carcinoma immune checkpoint inhibitors immune checkpoint blockade antibody-mediated thyroid dysfunction inflammatory gastrointestinal diseases nivolumab-related myasthenia gravis cancer\immunotherapy access anti-tnf-refractory colitis immune-related toxicities pembrolizumab-induced myasthenia gravis pd-1 blockade antibodies multi-institutional retrospective study preexisting autoimmune disorders pre-existing autoimmune preexisting autoimmune disease preexisting antinuclear antibodies privacy choices/manage cookies related subjects lopez-olivo ma checkpoint inhibitor therapy anti-pd-1 therapy full article pdf profiling preexisting antibodies translational oncology aims cytotoxic t-lymphocyte oncology meets immunology cmv-mediated immunopathogenesis ethics declarations conflict european economic area disease control rate identify predictive factors previously untreated melanoma previous chemotherapy regimens fatal case report gene expression profiling develop destructive thyroiditis individual participants included pd-1 inhibitors advanced malignancies treated important intellectual content

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         headline:Safety and efficacy of PD-1/PD-L1 blockade in patients with preexisting antinuclear antibodies
         description:Immune checkpoint inhibitors (ICIs) show promising clinical activity in advanced cancers. However, the safety and efficacy of PD-1/PD-L1 blockade in patients with preexisting antinuclear antibodies (ANA) are unclear. 191 patients treated with nivolumab, pembrolizumab, atezolizumab, or durvalumab for unresectable advanced cancers between September 2014 and December 2018 were identified retrospectively. Patients were divided into positive (ANA titers ≥ 1:160) and negative ANA groups (ANA titers < 1:160). Development of immune-related adverse events (irAEs), the overall response rate (ORR), and disease control rate (DCR) were monitored. Positive ANA titers were seen in 9 out of 191 patients. Four patients in the positive ANA group and 69 patients in the negative group developed irAEs of any grade without a significant difference between the groups. The development of endocrine, pulmonary, and cutaneous irAEs was not significant, whereas positive ANA was significantly higher in patients who developed colitis (2/9) than in patients who did not (3/182, P = 0.0002). DCR in the positive and negative ANA group was 37.5% and 67.5%, respectively, and was not statistically significant, but had better efficacy in patients without ANA (P = 0.08). ANA-related autoimmune diseases such as SLE, Sjögren's syndrome, MCTD, scleroderma, dermatomyositis, and polymyositis was not induced in either group. However, one patient with preexisting dermatomyositis had a flare up after initiation of atezolizumab. Further studies to identify predictive factors for the development of irAEs are required to provide relevant patient care and maximize the therapeutic benefits of ICIs.
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            Programmed cell death 1 blockade
            Immune checkpoint inhibitors
            Antinuclear antibodies
            Autoimmune diseases
            Oncology
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      headline:Safety and efficacy of PD-1/PD-L1 blockade in patients with preexisting antinuclear antibodies
      description:Immune checkpoint inhibitors (ICIs) show promising clinical activity in advanced cancers. However, the safety and efficacy of PD-1/PD-L1 blockade in patients with preexisting antinuclear antibodies (ANA) are unclear. 191 patients treated with nivolumab, pembrolizumab, atezolizumab, or durvalumab for unresectable advanced cancers between September 2014 and December 2018 were identified retrospectively. Patients were divided into positive (ANA titers ≥ 1:160) and negative ANA groups (ANA titers < 1:160). Development of immune-related adverse events (irAEs), the overall response rate (ORR), and disease control rate (DCR) were monitored. Positive ANA titers were seen in 9 out of 191 patients. Four patients in the positive ANA group and 69 patients in the negative group developed irAEs of any grade without a significant difference between the groups. The development of endocrine, pulmonary, and cutaneous irAEs was not significant, whereas positive ANA was significantly higher in patients who developed colitis (2/9) than in patients who did not (3/182, P = 0.0002). DCR in the positive and negative ANA group was 37.5% and 67.5%, respectively, and was not statistically significant, but had better efficacy in patients without ANA (P = 0.08). ANA-related autoimmune diseases such as SLE, Sjögren's syndrome, MCTD, scleroderma, dermatomyositis, and polymyositis was not induced in either group. However, one patient with preexisting dermatomyositis had a flare up after initiation of atezolizumab. Further studies to identify predictive factors for the development of irAEs are required to provide relevant patient care and maximize the therapeutic benefits of ICIs.
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      keywords:
         Immune-related adverse events
         Programmed cell death 1 blockade
         Immune checkpoint inhibitors
         Antinuclear antibodies
         Autoimmune diseases
         Oncology
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