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1.
Medicine (Baltimore) ; 98(41): e17348, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593084

RESUMO

Immune checkpoint inhibitors (ICIs) like cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4) and programmed death cell protein 1 (anti-PD1) have revolutionized cancer treatment. As ICI use becomes widespread, more immune-related adverse events (irAE's) are being reported. Our aim was to investigate the frequency and nature of new irAE's as well as report the frequency of flare-ups of pre-existing autoimmune conditions occurring after ICI therapy.We performed a retrospective chart review of all patients treated for cancer with anti-PD1 or anti-CTLA4 or combination therapy at our tertiary care center from January 2014 to April 2016. Demographic data, cancer type and stage, irAE's (new immune disorders and disease flares of pre-existing autoimmune disorders on ICI therapy), and drug treatment information were extracted.We identified 220 patients treated with ICI therapy during the study period out of which 27% (60/220) developed irAE's. 11% in anti-CTLA4 group and 16% among anti-PD1 treated patients developed irAE's. IrAE's resulted in discontinuation of cancer therapy in 28% of those who developed irAE's. 21.4% had a flare of their autoimmune disease but only 1 required discontinuation of immunotherapy.IrAE's are an important emerging clinical disease entity for specialists to be aware of. Our study shows that ICI's can be safely used in patients with pre-existing autoimmune conditions with close monitoring. However, there is still a large unmet need to have a better understanding of how to systematically evaluate and manage patients with irAE's as well as for identifying the predictors of irAE's.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Doenças do Sistema Imunitário/induzido quimicamente , Imunoterapia/efeitos adversos , Melanoma/tratamento farmacológico , Neoplasias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/imunologia , Antígeno CTLA-4/antagonistas & inibidores , Feminino , Humanos , Doenças do Sistema Imunitário/imunologia , Masculino , Melanoma/imunologia , Pessoa de Meia-Idade , Neoplasias/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Estudos Retrospectivos
2.
Ther Umsch ; 76(4): 195-198, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31498041

RESUMO

Immunotherapy - immune-related adverse events and their management Abstract. Checkpoint-Inhibition has become an important part of modern oncological treatment strategies for many patients with cancer. The development of this new class of anti-cancer drugs has begun for ten years and showed meanwhile a specific new side effect profile. Since the mode of action of checkpoint inhibitors is immune modulation the side effects are particularly different to so far established anti-cancer drugs. Because of the immunological nature of side effects, the spectrum is wide, and the symptoms are amble. Additionally, the side effects can appear at very different time points after the administration of the checkpoint inhibitor. Therefore, the recognition and the management are a new challenge for the care teams. Only if the whole care team is able to understand, diagnose and efficiently manage the side effects the therapeutic potential of this new class of anti-cancer drugs can be made useful for the patients. The article aims to provide information for the care teams to recognize and manage side effects of checkpoint-inhibitors.


Assuntos
Imunoterapia/efeitos adversos , Imunoterapia/métodos , Neoplasias/terapia , Humanos , Fatores Imunológicos , Oncologia , Síndromes Neurotóxicas/etiologia
3.
Eur J Endocrinol ; 181(3): R107-R118, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31311002

RESUMO

In recent years, the development of immunotherapy has constituted a revolution in the therapy for many cancers, with a specific toxicity profile including endocrine immune-related adverse events. Immune check point inhibitors (ICI)-induced hypophysitis is a common endocrine side effect, particularly with CTLA-4 antibodies and combination therapy, with frequent hormonal deficiencies at diagnosis. It can be difficult to evoke such diagnosis as the initial clinical symptoms are not specific (headache, asthenia…); thus, patients receiving such immunomodulatory therapies should be closely monitored by systematic hormone measurements, especially in the first weeks of treatment. Usually, hormonal deficiencies improve, except for corticotroph function. Despite a lack of large prospective studies on ICI-induced hypophysitis, some detailed longitudinal cohort studies have focused on such cases of hypophysitis and allow for optimal monitoring, follow-up and management of patients with this immune-related adverse event. In the case of ICI-induced hypophysitis, patients need long-term multidisciplinary follow-up, with specific education for those patients with corticotropin deficiency to allow them to be autonomous with their treatment. In this review, based on a clinical case, we detail the most relevant and novel aspects related to the incidence, diagnosis, treatment, evolution and management of hypophysitis induced by immunotherapy, with a focus on possible mechanisms and current recommendations and guidelines. Lastly, we emphasize several key points, such as the absence of indication to systematically treat with high-dose glucocorticoid and the pursuit of immunotherapy in such hypophysitis. These points should be kept in mind by oncologists and endocrinologists who treat and monitor patients treated by immunotherapy.


Assuntos
Antígeno CTLA-4/antagonistas & inibidores , Hipofisite/induzido quimicamente , Hipofisite/diagnóstico por imagem , Imunoterapia/efeitos adversos , Antígeno CTLA-4/sangue , Humanos , Hipofisite/sangue , Masculino , Pessoa de Meia-Idade
4.
Orv Hetil ; 160(23): 887-895, 2019 Jun.
Artigo em Húngaro | MEDLINE | ID: mdl-31155880

RESUMO

Oncotherapy has been revolutionised by the introduction of immune-checkpoint inhibitors including CTLA4, PD1 and PDL1 inhibitors. Patients with malignant diseases may largely benefit from these therapies, which may result in long-term remission even in the most therapy-resistant tumour types. Differences in the mode of action of the various agents may result in varying side-effect profiles. In addition to organ-specific side-effects, overt autoimmune syndromes may also develop. Our current view of oncotherapy has changed as these mostly immune-mediated side-effects highly differ from those observed previously during the administration of traditional anti-tumour compounds. These side-effects should be carefully characterized and differentiated from infections or the progression of the underlying malignancy. Fortunately, several recent recommendations have become available on the management of immune-mediated adverse events due to checkpoint-inhibitor therapy. Orv Hetil. 2019; 160(23): 887-895.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Fatores Imunológicos , Imunoterapia/efeitos adversos , Neoplasias/imunologia , Neoplasias/terapia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Imunoterapia/métodos , Oncologia , Neoplasias/patologia
5.
Expert Opin Ther Pat ; 29(7): 481-485, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31216214

RESUMO

Introduction: OX40 is checkpoint inhibitor in cancer that coordinates the downregulation of the proliferation of antigen-specific lymphocytes. There is a great need to discover and develop new therapies focused on inhibiting the action of OX40 and consequently improving the immune response in the various types of cancer. Authors of patent US2018256711A1 propose a method to eradicate cancer that utilizes anti-OX40 agonist antibody in combination with anti-PD-L1 antagonist antibody. Areas covered: Patent US2018256711A1 describes a method of cancer combinatorial treatment consisting of the utilization of a pharmaceutical cocktail containing anti-OX40 and an anti-PD-L1 antibody. Expert opinion: The results of the clinical trials only support trials regarding the tolerability of combinatorial therapy, even when the objectives of determining the safety and pharmacokinetics of the treatment are proposed.


Assuntos
Antígeno B7-H1/antagonistas & inibidores , Neoplasias/terapia , Receptores OX40/agonistas , Animais , Anticorpos/administração & dosagem , Anticorpos/imunologia , Humanos , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Neoplasias/imunologia , Neoplasias/patologia , Patentes como Assunto , Resultado do Tratamento
6.
Zhonghua Zhong Liu Za Zhi ; 41(6): 466-470, 2019 Jun 23.
Artigo em Chinês | MEDLINE | ID: mdl-31216835

RESUMO

Objective: To investigate the adrenocortical function changes of patients with advanced solid tumors who received the anti- programmed cell death protein-1 (PD-1) antibody, SHR-1210 therapy. Methods: The clinical data of 98 patients with advanced solid tumors who were enrolled in a prospective phase I trial of SHR-1210 therapy at our institution between April 27, 2016 and June 8, 2017 were collected. The levels of plasma adrenocorticotropic hormone (ACTH) and cortisol were evaluated in 96 patients. The clinical manifestations, laboratory tests and radiologic data were collected to define the immune-related adrenal insufficiency. Results: Until December 14th, 2018, no SHR-1210 related primary adrenal insufficiency occurred, and the incidence of immune-related secondary adrenal insufficiency was 1.0% among the 96 patients, which was identified as grade 2. No patient developed grade 3-4 adrenal insufficiency. The main clinical manifestations of the patient who was diagnosed as secondary adrenal insufficiency were grade 2 fatigue, anorexia and headache.The patient developed fatigue and anorexia at the 267th day after receiving the first dose of SHR-1210, the hypocortisolism occurred on the 279th day, and the headache emerged on the 291th day. The anorexia of patient who treated by physiological replacement doses of glucocorticoid since the 457th day was attenuated.The patient whose cortisol level was still below the normal limit continued to accept the hormone replacement therapy up to 776 days after the initial administration of SHR-1210. Conclusions: The incidence of SHR-1210 related adrenal insufficiency of patients with advanced solid tumors is low, and the symptoms can be effectively ameliorated by hormone replacement therapy. The potential adverse outcome of adrenal insufficiency following immunotherapy should be noticed by clinicians to avoid the occurrence of adrenal crisis.


Assuntos
Insuficiência Adrenal/epidemiologia , Anticorpos Monoclonais/efeitos adversos , Imunoterapia/efeitos adversos , Neoplasias/terapia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Humanos , Estudos Prospectivos
7.
Autoimmun Rev ; 18(8): 805-813, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31176871

RESUMO

Immune checkpoints are small molecules expressed by immune cells that play critical roles in maintaining immune homeostasis. Immune checkpoint inhibitors (ICPIs) are new cancer drugs that target self-tolerance pathways exploited by tumors to escape immune destruction, such as cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) or its ligand (PD-L1). Several ICPIs have been approved by Food and Drug Administration, increasing overall survival with different cancers. However, their use can determine development of many different inflammatory side effects, that are defined immune-related adverse effects (irAEs); among others, rheumatological irAEs can develop in these patients. Currently, we have limited data about these adverse effects; particularly, few evidence come from clinical trials about patients with pre-existing autoimmune diseases because they were excluded from them. Therefore we analysed the existing scientific literature dealing with this issue, in order to answer to different clinical questions. According to all reviewed data, rheumatological irAEs are not infrequent, in both previously diseased and undiseased patients, but they are often mild and reversible. Close monitoring and interdisciplinary management and monitoring is necessary in order to ensure best care. Many questions remain unanswered or not completely answered; further data are necessary to implement our knowledge in this field and to standardize and optimize clinical practice.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Imunoterapia/efeitos adversos , Neoplasias/tratamento farmacológico , Doenças Reumáticas/induzido quimicamente , Humanos , Neoplasias/imunologia
8.
Expert Rev Clin Pharmacol ; 12(6): 513-521, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31035801

RESUMO

Introduction: Advanced cancers that did not respond to chemotherapy were once a death sentence, but now there are newer therapies utilizing the patient's own immune system to fight cancer that are proving effective in chemotherapy-refractory malignancies. However, this success against cancer cells may be accompanied by immune-related adverse events that can affect the kidneys. Areas covered: Using Medline and Scopus, we compiled all publications through February 2019 that pertained to immune checkpoint inhibitors (ICPIs) and chimeric antigen receptor T-cells (CAR T-cells).  The focus of this review is the discussion of these new cancer therapies, with attention to the reported kidney-related adverse effects.. Expert opinion: Autoimmunity is repressed by molecular pathways that inhibit T-cell activation against selected antigens. These self-protective mechanisms have been appropriated by tumor cells as a means of evading immune detection and destruction. New immunotherapies such as immune checkpoint inhibitors and chimeric antigen receptor T-cell therapy incite an aggressive immune response directed against tumor cells. This unrestrained activation of the immune system may result in kidney injury via multiple mechanisms.


Assuntos
Imunoterapia/efeitos adversos , Nefropatias/etiologia , Neoplasias/terapia , Autoimunidade/imunologia , Humanos , Imunoterapia/métodos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Nefropatias/imunologia , Neoplasias/imunologia
9.
Int J Mol Sci ; 20(9)2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31067796

RESUMO

The therapeutic scenario for elderly patients with advanced NSCLC has been limited to radiotherapy and chemotherapy. Recently, a novel therapeutic approach based on targeting the immune-checkpoints has showed noteworthy results in advanced NSCLC. PD1/PD-L1 pathway is co-opted by tumor cells through the expression of PD-L1 on the tumor cell surface and on cells within the microenvironment, leading to suppression of anti-tumor cytolytic T-cell activity by the tumor. The success of immune-checkpoints inhibitors in clinical trials led to rapid approval by the FDA and EMA. Currently, data regarding efficacy and safety of ICIs in older subjects is limited by the poor number of elderly recruited in clinical trials. Careful assessment and management of comorbidities is essential to achieve better outcomes and limit the immune related adverse events in elderly NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Imunoterapia/métodos , Neoplasias Pulmonares/terapia , Receptor de Morte Celular Programada 1/imunologia , Fatores Etários , Idoso , Anticorpos Monoclonais/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Ensaios Clínicos como Assunto , Humanos , Imunoterapia/efeitos adversos , Neoplasias Pulmonares/epidemiologia
11.
Anticancer Res ; 39(4): 1699-1703, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30952708

RESUMO

BACKGROUND/AIM: Previous work in rodent models showed that an autologous tissue vaccine is both a safe and effective approach for treating cancer; however, as a translational step, safety must first be evaluated in a more clinically-relevant model. MATERIALS AND METHODS: An autologous immunotherapy produced from resected tumors, was evaluated in a clinically-relevant canine model to assess safety. Ninety-three dogs with spontaneously occurring tumors received vaccination with inactivated autologous tumor tissue combined with an adjuvant of particulate porcine small intestinal submucosa extracellular matrix (SIS-ECM). Patients were followed to assess the occurrence of adverse events, overall survival, and tumor recurrence and/or metastasis. RESULTS: A small number (12%) of patients experienced limited, mild pyrexia, injection site swelling, or lethargy, all resolving without clinical intervention. CONCLUSION: Autologous whole cell cancer immunotherapy can be used safely in the canine model of cancer and represents a safe approach for the treatment for cancer.


Assuntos
Antígenos de Neoplasias/administração & dosagem , Vacinas Anticâncer/administração & dosagem , Doenças do Cão/terapia , Imunoterapia/veterinária , Neoplasias/veterinária , Adjuvantes Imunológicos , Animais , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/toxicidade , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/toxicidade , Doenças do Cão/diagnóstico , Doenças do Cão/imunologia , Doenças do Cão/cirurgia , Cães , Feminino , Imunoterapia/efeitos adversos , Mucosa Intestinal/imunologia , Intestino Delgado/imunologia , Masculino , Margens de Excisão , Neoplasia Residual , Neoplasias/diagnóstico , Neoplasias/imunologia , Neoplasias/terapia , Sus scrofa
12.
Bull Cancer ; 106(5): 492-496, 2019 May.
Artigo em Francês | MEDLINE | ID: mdl-30981462

RESUMO

The management of cancer patients has changed due to the considerably more frequent use of immune checkpoint inhibitors (ICPI). However, the use of ICPI has a risk of side-effects, particularly endocrine toxicity. Since the indications for ICPI are constantly expanding due to their efficacy, it is important that endocrinologists and oncologists know how to look for this type of toxicity and how to treat it when it arises. In view of this, the French Endocrine Society initiated the formulation of a guidance document on ICPI-related endocrine toxicity. In this paper, we summarize the main insights of experts' opinions, from an oncologist viewpoint: initial screening, monitoring, emergency situations for which immediate management by the oncologist is crucial, as well as the roles of the interactions between oncologists and endocrinologists. These points will be detailed for each endocrinopathy, i.e., dysthyroidism, hypophysitis, fulminant diabetes and primary adrenal insufficiency. In each chapter, expert opinion will be given on the diagnosis, management and monitoring for each complication. Finally, the CTCAE (Common terminology criteria for adverse events) recommendations will be discussed in view of the relatively easy management of such endocrine side-effects.


Assuntos
Doenças do Sistema Endócrino/etiologia , Imunoterapia/efeitos adversos , Humanos
13.
J Cancer Res Clin Oncol ; 145(6): 1527-1557, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31028541

RESUMO

INTRODUCTION: The advent of immune checkpoint inhibitors in the treatment of certain types of cancers has revolutionized cancer therapy. In general, these novel agents are more tolerable and have better safety profiles than conventional chemotherapy agents. Although a low incidence of myocarditis was noted as a side effect of immune checkpoint inhibitors in clinical trials, it is being increasingly cited in the literature as their use also increases. METHODS: Using a combination of search terms in the PubMed/Medline database and manual searches on Google Scholar and the bibliographies of articles identified, we reviewed all cases reported in the English language citing myocarditis associated with either pembrolizumab, nivolumab, ipilimumab, or any combination of these agents. RESULTS: A total of 42 cases were included in the study. Mean age was 65.5 years; 64% were male, 36% were female. One or two doses preceded the onset of myocarditis in 33% and 29% of cases, respectively. Steroids were used as the first-line therapy in 90% of cases. Complete heart block occurred in 36% of cases. Fourteen (33%) deaths were reported, with 64% and 29% of deaths occurring after one or two doses, respectively. CONCLUSION: Most cases and fatalities of myocarditis occurred shortly after initiation of immune checkpoint inhibitor therapy. Arrhythmias, particularly complete heart block, appear to be related to the occurrence of more severe and fatal cases. The use of serial electrocardiograms or biomarkers of myocardial injury may be crucial in detecting early stages of the disease process. Further research establishing more specific guidelines is necessary in dealing with this potentially fatal side effect.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Miocardite/epidemiologia , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Feminino , Humanos , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Imunoterapia/estatística & dados numéricos , Ipilimumab/administração & dosagem , Ipilimumab/efeitos adversos , Masculino , Pessoa de Meia-Idade , Miocardite/induzido quimicamente , Miocardite/imunologia , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos
14.
Actas dermo-sifiliogr. (Ed. impr.) ; 110(3): 182-192, abr. 2019. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-181707

RESUMO

Las nuevas terapias inmunológicas dirigidas contra el cáncer han supuesto un cambio radical en el tratamiento y el pronóstico de muchas neoplasias. Estos medicamentos se dirigen de manera mucho más específica contra los mecanismos fisiopatogénicos del cáncer, por lo que adquieren el sobrenombre de "terapias diana". Este cambio de paradigma ha supuesto la aparición de nuevos efectos adversos dermatológicos, que afectan tanto la piel como sus anejos. Los efectos adversos en el pelo pueden manifestarse en alteraciones de su ciclo, forma, color o inmunología. Debido a que son tratamientos nuevos en su mayoría y no existe un documento que englobe todos estos efectos adversos, hemos realizado una exhaustiva revisión bibliográfica para caracterizar de manera concreta cuáles son los efectos adversos tricológicos que pueden inducir cada uno de estos fármacos


The advent of immune targeted therapies for cancer has radically changed the treatment and prognosis of many cancers. These drugs are called targeted therapies because they target specific pathophysiological mechanisms of cancer. This paradigm shift in cancer treatment, however, has resulted in new adverse dermatologic effects involving both the skin and its appendages. In the case of hair, targeted drugs can cause immune alterations and changes in hair growth, color, and shape. Because most targeted therapies are new, there is no single document describing all these adverse effects. We performed an exhaustive review of the literature to characterize adverse hair effects associated with the use of targeted therapies


Assuntos
Humanos , Antineoplásicos/efeitos adversos , Erupção por Droga/etiologia , Terapia de Alvo Molecular/efeitos adversos , Cor de Cabelo/efeitos dos fármacos , Imunoterapia/efeitos adversos , Doenças do Cabelo/induzido quimicamente , Alopecia/induzido quimicamente , Fatores Imunológicos/efeitos adversos
15.
Clin Nucl Med ; 44(6): e392-e393, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30932979

RESUMO

Several regimens of immunotherapy have recently proven successful for multiple cancers, due to increased survival and quality of life. Rarely, immunotherapy with anti-programmed cell death protein 1 and programmed death-ligand 1 antibodies across cancer may cause immune-related pulmonary toxicity, with a low overall incidence, being particularly low among patients with melanoma and highest among individuals with lung cancer. In this vein, pulmonary toxicity is staged at 4 degrees according to the severity of the clinic and radiological findings, and its management is based on suppression of immunotherapy and administration of glucocorticoids. We report a case of pulmonary toxicity related to melanoma immunotherapy observed by F-FDG PET/CT.


Assuntos
Imunoterapia/efeitos adversos , Melanoma/terapia , Pneumonia/etiologia , Adulto , Fluordesoxiglucose F18 , Humanos , Masculino , Melanoma/imunologia , Pneumonia/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Qualidade de Vida
16.
Cancer Immunol Immunother ; 68(6): 917-926, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30877325

RESUMO

INTRODUCTION: Patients with pre-existing autoimmune diseases have been excluded from clinical trials of immune checkpoint inhibitors (ICIs) for cancer. Real-world evidence is necessary to understand ICI safety in this population. METHODS: Patients treated with ICIs from 2011 to 2017 were identified using data from a large health insurer. Outcomes included time to (1) any hospitalization; (2) any hospitalization with an irAE diagnosis; and (3) outpatient corticosteroid treatment. The key exposure was pre-existing autoimmune disease, ascertained within 12 months before starting ICI treatment, and defined either by strict criteria (one inpatient or two outpatient claims at least 30 days apart) or relaxed criteria only (any claim, without meeting strict criteria). RESULTS: Of 4438 ICI-treated patients, pre-existing autoimmune disease was present among 179 (4%) by strict criteria, and another 283 (6%) by relaxed criteria only. In multivariable models, pre-existing autoimmune disease by strict criteria was not associated with all-cause hospitalization (HR 1.27, 95% CI 0.998-1.62), but it was associated with hospitalization with an irAE diagnosis (HR 1.81, 95% CI 1.21-2.71) and with corticosteroid treatment (HR 1.93, 95% CI 1.35-2.76). Similarly, pre-existing autoimmune disease by relaxed criteria only was not associated with all-cause hospitalization (HR 1.11, 95% CI 0.91-1.34), but was associated with hospitalization with an irAE diagnosis (HR 1.46, 95% CI 1.06-2.01) and corticosteroid treatment (HR 1.46, 95% CI 1.13-1.88). CONCLUSION: Pre-existing autoimmune disease was not associated with time to any hospitalization after initiating ICI therapy, but it was associated with a modest increase in hospitalizations with irAE diagnoses and with corticosteroid treatment.


Assuntos
Anticorpos Monoclonais/imunologia , Doenças Autoimunes/imunologia , Antígeno B7-H1/imunologia , Antígeno CTLA-4/imunologia , Neoplasias/imunologia , Receptor de Morte Celular Programada 1/imunologia , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Doenças Autoimunes/complicações , Doenças Autoimunes/tratamento farmacológico , Antígeno B7-H1/antagonistas & inibidores , Antígeno CTLA-4/antagonistas & inibidores , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Seguro Saúde/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias/complicações , Neoplasias/terapia , Receptor de Morte Celular Programada 1/antagonistas & inibidores
17.
BMJ Case Rep ; 12(2)2019 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30819683

RESUMO

Nivolumab is an immune checkpoint inhibitor that is used in the treatment of a variety of cancers in the adjuvant or metastatic setting. Adverse effects include non-specific activation of T cells, leading to immune-related adverse events in downstream organs. We present a case of a 36-year-old man with unresectable oropharyngeal squamous cell carcinoma who developed nivolumab-induced rheumatoid arthritis. As immune checkpoint inhibitor use is becoming widespread in the medical oncology domain, the purpose of this case report is to increase awareness of an increasingly common cause of rheumatic disease and to alert clinicians to consider immunotherapy in their differential diagnosis of polyarthritis. This case also highlights the importance of working in an interdisciplinary manner to enhance cancer care for the patient as well as to increase awareness of the potential adverse effects of immunotherapy in patients with cancer.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/diagnóstico por imagem , Imunoterapia/efeitos adversos , Nivolumabe/efeitos adversos , Adulto , Artralgia/etiologia , Diagnóstico Diferencial , Humanos , Imunoterapia/métodos , Articulações/diagnóstico por imagem , Masculino , Radiografia , Ultrassonografia
18.
Trials ; 20(1): 156, 2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30832742

RESUMO

BACKGROUND: Peritonitis is responsible for thousands of deaths annually in Germany alone. Even source control (SC) and antibiotic treatment often fail to prevent severe sepsis or septic shock, and this situation has hardly improved in the past two decades. Most experimental immunomodulatory therapeutics for sepsis have been aimed at blocking or dampening a specific pro-inflammatory immunological mediator. However, the patient collective is large and heterogeneous. There are therefore grounds for investigating the possibility of developing personalized therapies by classifying patients into groups according to biomarkers. This study aims to combine an assessment of the efficacy of treatment with a preparation of human immunoglobulins G, A, and M (IgGAM) with individual status of various biomarkers (immunoglobulin level, procalcitonin, interleukin 6, antigen D-related human leucocyte antigen (HLA-DR), transcription factor NF-κB1, adrenomedullin, and pathogen spectrum). METHODS/DESIGN: A total of 200 patients with sepsis or septic shock will receive standard-of-care treatment (SoC). Of these, 133 patients (selected by 1:2 randomization) will in addition receive infusions of IgGAM for 5 days. All patients will be followed for approximately 90 days and assessed by the multiple-organ failure (MOF) score, by the EQ QLQ 5D quality-of-life scale, and by measurement of vital signs, biomarkers (as above), and survival. DISCUSSION: This study is intended to provide further information on the efficacy and safety of treatment with IgGAM and to offer the possibility of correlating these with the biomarkers to be studied. Specifically, it will test (at a descriptive level) the hypothesis that patients receiving IgGAM who have higher inflammation status (IL-6) and poorer immune status (low HLA-DR, low immunoglobulin levels) have a better outcome than patients who do not receive IgGAM. It is expected to provide information that will help to close the knowledge gap concerning the association between the effect of IgGAM and the presence of various biomarkers, thus possibly opening the way to a personalized medicine. TRIAL REGISTRATION: EudraCT, 2016-001788-34; ClinicalTrials.gov, NCT03334006 . Registered on 17 Nov 2017. Trial sponsor: RWTH Aachen University, represented by the Center for Translational & Clinical Research Aachen (contact Dr. S. Isfort).


Assuntos
Imunoglobulina A/administração & dosagem , Imunoglobulina G/administração & dosagem , Imunoglobulina M/administração & dosagem , Imunoglobulinas Intravenosas/administração & dosagem , Imunoterapia/métodos , Peritonite/terapia , Medicina de Precisão/métodos , Sepse/terapia , Antibacterianos/uso terapêutico , Áustria , Biomarcadores/sangue , Tomada de Decisão Clínica , Alemanha , Humanos , Imunoglobulina A/efeitos adversos , Imunoglobulina G/efeitos adversos , Imunoglobulina M/efeitos adversos , Imunoglobulinas Intravenosas/efeitos adversos , Imunoterapia/efeitos adversos , Infusões Intravenosas , Estudos Multicêntricos como Assunto , Seleção de Pacientes , Peritonite/diagnóstico , Peritonite/imunologia , Peritonite/microbiologia , Medicina de Precisão/efeitos adversos , Valor Preditivo dos Testes , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sepse/diagnóstico , Sepse/imunologia , Sepse/microbiologia , Fatores de Tempo , Resultado do Tratamento
19.
BMJ Case Rep ; 12(3)2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30837232

RESUMO

Our patient, who had been previously diagnosed with non-small cell lung cancer, presented with progressive dyspnoea after receiving second-line immunotherapy treatment with atezolizumab. Chest CT scan showed bilateral lung architectural distortion, bronchial dilatation, consolidative opacities, ground-glass opacities and linear opacities concerning for either infectious lung disease or treatment-related lung disease. A diagnostic bronchoscopy was performed and no evidence of malignancy or infection was detected. Discontinuing atezolizumab with the addition of oral corticosteroid improved the patient's respiratory symptoms but the patient required continuous oxygen supplementation. Later, the patient was found to have radiologic findings suggestive of further progression of his pneumonitis after completion of a course of corticosteroid treatment and required another course of oral prednisone. Immune-mediated pneumonitis could present with mild to severe respiratory symptoms with a wide range of clinical and radiologic features and physicians should be aware of this diagnosis of exclusion. Although patients may experience progressive disease with or without immunotherapy rechallenge, most of these cases can be managed successfully with favourable outcomes.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Imunoterapia/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Pneumonia/induzido quimicamente , Idoso , Anticorpos Monoclonais/administração & dosagem , Broncoscopia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Pneumonia/fisiopatologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
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