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Cardiotoxicities are associated with immune checkpoint inhibitor (ICI) therapy. Recent case series and retrospective studies have shown that cardiac immune‐related adverse events (irAEs) are rare but potentially fatal complications of immunotherapy, with various underlying risk factors such as combinations of different ICIs. High mortality rates and overreactive inflammation have been observed with ICI‐associated cardiotoxicities, highlighting the necessity of baseline and serial evaluations and the identification and management of cardiac irAEs as early as possible. The clinical presentations of irAEs range from asymptomatic cardiac biomarker elevation, myocarditis and pericardial diseases to heart failure and mild to fatal arrhythmia. Troponin measurement and electrocardiogram are sensitive initial tests, whereas cardiac magnetic resonance imaging and endomyocardial biopsy are both gold standard components of the diagnostic criteria. Close monitoring and timely consultation with a cardiologist are important for the diagnosis of ICI‐related cardiotoxicities, with decisions of stopping or rechallenging ICIs and strategies to manage heart injuries. Treatment principles are made according to risk stratifications. The first‐line medication is glucocorticoids of various doses, and the second‐line immunosuppression includes intravenous immunoglobin, antithymocyte globulin and other immunosuppressants, which are recommended in life‐threatening cases or in cases of resistance/no response to steroids. 相似文献
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《Clinical lung cancer》2022,23(8):686-693
BackgroundDespite their anti-tumor efficacy, immune checkpoint inhibitors (ICIs) are associated with a variety of immune-related adverse events (irAEs). Grade ≥ 2 irAEs require ICI discontinuation. The decision to resume ICI treatment often remains challenging.MethodsWe retrospectively studied 1051 adult patients with stage IV non-small cell lung cancer (NSCLC) treated with ICIs at a single institution between January 2015 and December 2020, and identified 99 (9.4%) patients with grade≥2 irAEs necessitating treatment interruption. Forty patients underwent retreatment (rechallenged group), while 59 discontinued the treatment (discontinued group).ResultsBaseline characteristics of patients in the 2 groups were similar. Initial irAEs were less severe in the rechallenged group. After rechallenging, 24 of 40 (60%) patients had recurrence of the same or de-novo irAEs. Twenty (50%) developed second grade≥ 2 irAEs. No grade 4 irAE or irAE-related death occurred after rechallenging. Using multivariate analysis, no statistically significant differences in overall survival (OS) (HR: 1.10, 95% CI: 0.57-2.15, P = .77) or progression-free survival (PFS) (HR: 0.87, 95% CI: 0.45-1.71, P = .69) were noted between the 2 groups, while the best objective response prior to the initial irAEs was the only variable affecting OS and PFS.ConclusionsRechallenge was associated with a relative high risk of second grade≥ 2 irAEs. The risk was less if the initial irAEs were resolved. No differences were seen in survival outcomes of patients who had ICI rechallenge and those who did not. Permanent ICI discontinuation is an appropriate strategy after grade≥ 2 irAEs, especially severe irAEs. 相似文献
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《Journal of thoracic oncology》2021,16(3):381-394
Immune checkpoint inhibitors (ICIs) have transformed the prognosis of cancers previously considered lethal. The spectrum of therapeutic indications is rapidly expanding, including the vast majority of thoracic malignancies. By enhancing the immune responses against cancer, the ICI treatments lead to the development of immune-related adverse events (irAEs) that may affect any organ. Severity varies from mild to fatal clinical manifestations. Neurologic involvement is relatively rare and highly heterogeneous, including central and peripheral nervous system diseases associated with neural-specific autoantibodies or not, central nervous system vasculitis, and granulomatous and demyelinating disorders. Symptoms often manifest within the first four cycles of treatment and can develop regardless of the class of ICI used. An unfavorable outcome is found in up to one-third of patients and is generally associated with the patients’ clinical characteristics (e.g., age, coexistence of systemic adverse events), cancer type (e.g., lung cancer versus other), and specific clinical setting (e.g., ICI treatment in patients with preexisting paraneoplastic neurologic autoimmunity, ICI rechallenge after a first neurologic irAE). Diagnosis should be suspected in patients with new-onset neurologic symptoms while on ICI treatment which are not explained by metastatic disease or other metabolic/infectious disorders. Recommended treatment is based on clinical severity and consists of ICI discontinuation with or without immunosuppressive/immunomodulatory therapy, although alternative approaches are reasonable depending on cancer status (e.g., aggressive immunosuppression without discontinuing ICI in patients with initial cancer response). Early recognition and appropriate treatment of these neurologic irAEs are crucial for improved patient outcomes and therapeutic planning. 相似文献
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近年来,通过增强机体免疫系统对肿瘤细胞的杀伤作用,免疫检查点抑制剂(immune checkpoint inhibitor,ICI)在抗肿瘤治疗中的应用获得了显著的临床疗效.然而,多项证据表明,免疫治疗在激活免疫系统的同时可导致独特的免疫相关不良反应(immune-related adverse event,irAE)... 相似文献
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Chiaki Kurimoto Hidefumi Inaba Hiroyuki Ariyasu Hiroshi Iwakura Yoko Ueda Shinsuke Uraki Ken Takeshima Yasushi Furukawa Shuhei Morita Yuki Yamamoto Shimpei Yamashita Masahiro Katsuda Atsushi Hayata Hiroaki Akamatsu Masatoshi Jinnin Isao Hara Hiroki Yamaue Takashi Akamizu 《Cancer science》2020,111(5):1468-1477
Immune‐related adverse events (irAEs) are often seen during immune‐checkpoint inhibitor (ICI) treatment of various malignancies. Endocrine irAEs including thyroid dysfunctions are the most common irAEs, but their biomarkers remain unclear. In order to identify individuals who are susceptible to thyroid irAE for earlier diagnosis and appropriate follow‐up, the current study is aimed to investigate biomarkers of thyroid irAE. Herein, patients with advanced malignant diseases who received ICIs treatment were prospectively studied. Clinical and laboratory examination, thyroid function, and autoantibodies were evaluated at baseline, and every 4 wk after first treatment with ICIs. Cytokines/chemokines were measured at baseline and at 4 wk. In vivo effects of ICIs on experimental autoimmune thyroiditis were evaluated. Twenty‐six patients with malignant diseases who received ICIs treatment were enrolled in the study. Patients were divided into two groups: those who developed thyroid irAE, and those without irAEs. Comparing the two groups, early increase (≤4 wk) in serum thyroglobulin (Tg) levels and thyroid autoantibodies was seen in thyroid irAE (P < .05). Notably, higher levels of serum IL‐1β, IL‐2, and GM‐CSF at baseline, and early decrease of IL‐8, G‐CSF, and MCP‐1 were significantly associated in the development of thyroid irAE (P < .05). In vivo effects of anti‐PD‐1 antibody on deterioration of mice experimental thyroiditis were seen. In conclusion, early change in Tg, thyroid autoimmunity, and cytokine levels might indicate development of thyroid irAE. Pre‐existing thyroid autoimmunity might be involved with the development of thyroid irAE. Potential application of these factors as surrogate biomarkers for tumor therapy was indicated. 相似文献
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目的:描述中国人群中免疫检查点抑制剂(ICI)相关不良事件(AEs)的状况。方法:截止至2019年9月22日,检索PubMed、Web of Science和Embase数据库中所有ICI相关的临床试验,入组中国患者或主要是中国人群的试验将会被纳入本研究,汇总并比较治疗相关不良事件(TRAE)和免疫相关不良事件(irAE)的发生率。结果:纳入13个试验合计1 063例患者,其中922(86.7%)例接受ICI单药治疗,141(13.3%)例接受ICI联合化疗或抗血管生成治疗。在所有患者中,任意级别的TRAE、1-2级TRAE、3-5级TRAE、任意级别irAE、1-2级irAE、3-5级irAE的累计发生率分别为84.1%、63.3%、20.9%、43.3%、40.0%、3.0%;与ICI单药治疗相比,ICI联合化疗或抗血管治疗显著提高了3-5级TRAE(46.1% vs 17.0%,P<0.001)和3-5级irAE(7.1% vs 2.0%,P=0.015)。通过比较不同ICI之间的毒性谱,我们发现了一些药物特异性不良反应。结论:ICI相关的不良事件一般为轻度,中国人群耐受性良好。但是,当ICI与化疗或抗血管治疗联合使用时,3-5级的TRAE和irAE会显著增加。 相似文献
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《Journal of Geriatric Oncology》2020,11(3):523-528
ObjectivesImmune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer, but outcomes in older adults are not well defined. We evaluated the associations of geriatric assessment (GA) domains with treatment-related outcomes in older adults with solid tumors receiving ICIs.MethodsWe performed a single-center, retrospective study of patients age ≥65 years diagnosed with solid tumors who received ICIs and were evaluated with a GA from January 2011 to April 2017. Using Wilcoxon rank sum test, we examined the associations of GA domains and treatment-related outcomes, including the number of ICI cycles received, best response, immune-related adverse events (irAEs), and hospitalizations during ICI treatment.ResultsWe identified 28 patients (median age at ICI treatment = 78 years, range 66–93); 60% had Eastern Cooperative Oncology Group (ECOG) Performance Status of ≥2; 39% had lung cancer; 89% had stage IV cancer; and 50% received pembrolizumab. Seventy-five percent had at least one GA domain impairment. Patients with any instrumental activities of daily living (IADL) impairment received fewer cycles of ICI (median: 2.0 vs. 7.0 cycles, p = 0.02). In this small sample, neither age nor GA domain measures were associated with best response, irAEs, or hospitalization during ICI treatment.ConclusionsOlder adults treated with ICIs had a high prevalence of impairments in GA domains, and IADL impairments were associated with shorter duration of ICI treatment. Future prospective studies are needed to evaluate the role of the GA further in this vulnerable patient population in the immunotherapy era. 相似文献
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Hiroaki Akamatsu Eriko Murakami Jun Oyanagi Ryota Shibaki Takahiro Kaki Eri Takase Masanori Tanaka Yuhei Harutani Nao Yamagata Yuka Okuda Katsuyuki Furuta Takeya Sugimoto Shunsuke Teraoka Atsushi Hayata Nahomi Tokudome Yuichi Ozawa Keita Mori Yasuhiro Koh Nobuyuki Yamamoto 《The oncologist》2020,25(4):e679-e683
Background
Although predictive value of immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) have been suggested by several studies, their assessments were insufficient because patients were categorized only by the occurrence of irAEs. It has not been elucidated whether irAEs also play a significant role even in responders.Materials and Methods
Between December 2015 and September 2018, 106 patients with advanced non-small cell lung cancer treated with ICIs were enrolled in our prospective biomarker study. Twenty-three of these were responders, defined as those with complete or partial response. We investigated the proportion of irAEs among overall and responders. For responders, progression-free survival (PFS) and overall survival of ICIs were compared between those with and without irAEs. As an exploratory analysis, we measured 41 proteins from peripheral blood before and after ICI treatment.Results
The proportion of irAEs was significantly higher in responders than nonresponders (65.2% vs. 19.3%, p < .01). Among responders, clinical characteristics did not differ regardless of the occurrence of irAEs. However, there was a significant difference in PFS among responders (irAE group 19.1 months vs. non-irAE group 5.6 months; hazard ratio: 0.30 [95% confidence interval: 0.10–0.85]; p = .02). Of 41 protein analyses, fibroblast growth factor-2 at baseline and monocyte chemoattractant protein fold change showed significant differences between them (p < .04).Conclusion
Although this is a small sample–sized study, irAE might be a predictive factor of durable efficacy, even in patients who responded to ICIs. Investigation into the significance of irAEs in responders will contribute to the establishment of optimal administration of ICI.Implications for Practice
Although the predictive value of immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) has been suggested by several studies, it has not been elucidated whether irAEs also play a significant role even in responders. This study showed that more than 60% of responders had irAEs. It demonstrated the strong correlation between irAEs and efficacy even in responders. Investigation into the significance of irAEs in responders will contribute to the establishment of optimal administration of ICI.11.
Immune-related adverse events in older adults: Data mining of the FDA Adverse Event Reporting System
《Journal of Geriatric Oncology》2022,13(7):1017-1022
IntroductionRecent studies reveal that there is no difference in the efficacy of immune checkpoint inhibitors (ICIs) between younger adults and older adults. However, it remains unclear whether age is a risk factor for immune-related adverse events (irAEs).Materials and methodsTo analyze the association between irAEs and age based on data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database between January 2004 and December 2020, we performed a case/noncase study on ICI-related adverse events. Cases were defined as adverse event cases with ICI therapy and irAEs, and noncases were defined as adverse event cases with ICI therapy and without irAEs. One case was matched to a noncase using the sex, reporter, report year, and type of ICI regimen. The reporting odds ratios (RORs) were used to assess the disproportionality of irAEs between older adults (≥65 years) and younger adults (<65 years).ResultsThe study shows that compared with younger adults, the ROR of older adults was 1.12 (95% confidence interval [CI]: 1.08–1.16) and 1.18 (95% CI: 1.14–1.23) before and after matching, respectively. The signal of age-related irAEs was detected in patients treated with ICI monotherapy but not in patients treated with combination therapy. Further analysis revealed a spectrum of age-related toxicities including cardiovascular toxicities, lung toxicities, musculoskeletal toxicities, nervous system toxicities, renal toxicities, and skin toxicities.ConclusionIn this analysis performed based on the FAERS, irAE cases were more likely to be reported in older adults. Our pharmacovigilance study complements the safety data of clinical trials. Further studies are expected to explore the underlying reasons for irAEs in older adults. 相似文献
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Mark A. Baxter Fearghas Middleton Hannah P. Cagney Russell D. Petty 《British journal of cancer》2021,125(8):1068
Immune checkpoint inhibitors (ICIs) have altered the treatment paradigm across a range of tumour types, including gastro-oesophageal cancers. For patients with any cancer type who respond, ICIs can confer long-term disease control and significantly improve survival and quality of life, but for patients with gastro-oesophageal cancer, ICIs can be transformative, as durable responses in advanced disease have hitherto been rare, especially in those patients who are resistant to first-line cytotoxic therapies. Results from trials in patients with advanced-stage gastro-oesophageal cancer have raised hopes that ICIs will be successful as adjuvant and neoadjuvant treatments in early-stage disease, when the majority of patients relapse after potential curative treatments, and several trials are ongoing. Unfortunately, however, ICI-responding patients appear to constitute a minority subgroup within gastro-oesophageal cancer, and resistance to ICI therapy (whether primary or acquired) is common. Understanding the biological mechanisms of ICI resistance is a current major research challenge and involves investigation of both tumour and patient-specific factors. In this review, we discuss the mechanisms underlying ICI resistance and their potential specific applications of this knowledge towards precision medicine strategies in the management of gastro-oesophageal cancers in clinical practice.Subject terms: Gastric cancer, Oesophageal cancer 相似文献
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免疫检查点抑制剂(ICI)作为新型免疫治疗手段,是继化疗、靶向治疗、抗血管生成治疗后又一新兴的抗肿瘤治疗方式,已经为恶性肿瘤患者带来了显著的生存获益。但其产生的免疫相关不良反应(irAE)的总体发生率达79%~82%,irAE极大地影响了临床治疗决策,且在一定程度上限制了其临床应用和患者持续获益。几乎患者的所有器官系统都可能受到irAE的影响,其广谱性、特殊性、复杂性和多样性极大地增大了临床诊治的难度。充分认识和早期识别重度irAE对于避免发生危重症毒性相关的死亡尤为重要,危重症irAE特别需要多学科诊疗协作组(MDT)的联合应对。对诊断不明的、病情危重的、治疗效果欠佳的irAE,或者毒性缓解后是否重启免疫治疗的患者均需要规范化、标准化的MDT诊疗,故建立以患者为中心的irAE-MDT模式,以循证医学和相关指南/共识为依据,救治危重疑难irAE,将使肿瘤患者从免疫治疗中获益最大化。 相似文献
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目的:探讨免疫检查点抑制剂(ICI)治疗非小细胞肺癌(NSCLC)产生的免疫相关不良反应(irAE)及ICI相关肺炎(ICI-P)的特点及其危险影响因素。方法:回顾性分析2019年1月到2021年12月间在山西白求恩医院胸部肿瘤科接受至少1次ICI治疗的114例NSCLC患者的一般性资料和临床特征的基线特征、治疗细节和发生irAE、ICI-P的数据,分析患者临床特征与irAE及ICI-P的关系,分析ICI-P发生的危险因素。观察ICI-P患者临床特点和治疗效果。结果:114例接受ICI治疗的NSCLC患者中有48例(42.11%)发生68次irAE,整体和严重irAE的发生率分别是59.65%、9.65%;从高到低排列发生率(仅列出前四位):消化系统>呼吸系统>皮肤>内分泌系统;使用信迪利单抗>度伐利尤单抗>卡瑞利珠单抗=帕博利珠单抗;临床特征中的年龄与irAE发生有关联。15例患者发生ICI-P,整体发生率为13.16%,占irAE患者的31.25%,其中4例为重症,占irAE数的8.33%、ICI-P数的26.66%;发生于联合治疗的多于单药治疗(73... 相似文献
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Tsuyoshi Isawa Yukihiro Toi Shunichi Sugawara Masataka Taguri Shigeru Toyoda 《The oncologist》2022,27(5):e410
BackgroundCardiovascular immune-related adverse events (CV–irAEs) associated with immune checkpoint inhibitors (ICIs) may have been underreported given that most previous reports were retrospective. We aimed to evaluate the incidence, clinical characteristics, and predictors of CV–irAEs and determine the feasibility of serial cardiac monitoring using a combination of B-type natriuretic peptide, cardiac troponin T, and electrocardiogram for the prediction of future symptomatic (grade ≥2) CV–irAEs.Materials and MethodsThis was a prospective observational study that included 129 consecutive patients with non–small-cell lung cancer who received ICI monotherapy at a single center. Serial cardiac monitoring was performed during ICI monotherapy.ResultsA total of 35 (27%) patients developed any grade ≥1 CV–irAEs with a median time of onset of 72 (interquartile range 44-216) days after ICI treatment initiation. Multivariate Fine–Gray regression analysis showed that prior acute coronary syndrome (adjusted hazard ratio [HR] 3.15 (95% [CI], 2.03-4.91), prior heart failure hospitalization (adjusted HR 1.65 [95% CI, 1.17-2.33]), and achievement of disease control (adjusted HR 1.91, [95% CI, 1.16-3.14]) were significantly associated with grade ≥1 CV–irAEs. Serial cardiac monitoring revealed that patients with preceding grade 1 CV–irAEs were associated with a significantly higher risk of onset of grade ≥2 CV–irAEs compared with those without preceding grade 1 CV–irAEs (HR: 6.17 [95% CI, 2.97-12.83]).ConclusionCV–irAEs were more common than previously recognized and have several predictors. Moreover, serial cardiac monitoring may be feasible for the prediction of future grade ≥2 CV–irAEs. 相似文献
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Yusuke Kagawa Hiromi Furuta Takehiro Uemura Naohiro Watanabe Junichi Shimizu Yoshitsugu Horio Hiroaki Kuroda Yoshitaka Inaba Takeshi Kodaira Katsuhiro Masago Shiro Fujita Akio Niimi Toyoaki Hida 《Cancer science》2020,111(12):4442
Immune checkpoint inhibitors (ICIs) have dramatically changed the strategy used to treat patients with non‐small‐cell lung cancer (NSCLC); however, the vast majority of patients eventually develop progressive disease (PD) and acquire resistance to ICIs. Some patients experience oligoprogressive disease. Few retrospective studies have evaluated clinical efficacy in patients with oligometastatic progression who received local therapy after ICI treatment. We conducted a retrospective analysis of advanced NSCLC patients who received PD‐1 inhibitor monotherapy with nivolumab or pembrolizumab to evaluate the effects of ICIs on the patterns of progression and the efficacy of local therapy for oligoprogressive disease. Of the 307 patients treated with ICIs, 148 were evaluated in our study; 42 were treated with pembrolizumab, and 106 were treated with nivolumab. Thirty‐eight patients showed oligoprogression. Male sex, a lack of driver mutations, and smoking history were significantly correlated with the risk of oligoprogression. Primary lesions were most frequently detected at oligoprogression sites (15 patients), and 6 patients experienced abdominal lymph node (LN) oligoprogression. Four patients showed evidence of new abdominal LN oligometastases. There was no significant difference in overall survival (OS) between the local therapy group and the switch therapy group (reached vs. not reached, P = .456). We summarized clinical data on the response of oligoprogressive NSCLC to ICI therapy. The results may help to elucidate the causes of ICI resistance and indicate that the use of local therapy as the initial treatment in this setting is feasible treatment option. 相似文献
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Dylan J. Martini Subir Goyal Yuan Liu Sean T. Evans T. Anders Olsen Katherine Case Benjamin L. Magod Jacqueline T. Brown Lauren Yantorni Greta Anne Russler Sarah Caulfield Jamie M. Goldman Bassel Nazha Wayne B. Harris Haydn T. Kissick Viraj A. Master Omer Kucuk Bradley C. Carthon Mehmet Asim Bilen 《The oncologist》2021,26(10):e1742-e1750
Background
Immune checkpoint inhibitors (ICIs) are an important treatment for metastatic renal cell carcinoma (mRCC). These agents may cause immune-related adverse events (irAEs), and the relationship between irAEs and outcomes is poorly understood. We investigated the association between irAEs and clinical outcomes in patients with mRCC treated with ICIs.Methods
We performed a retrospective study of 200 patients with mRCC treated with ICIs at Winship Cancer Institute from 2015 to 2020. Data on irAEs were collected from clinic notes and laboratory values and grades were determined using Common Terminology Criteria in Adverse Events version 5.0. The association with overall survival (OS) and progression-free survival (PFS) was modeled by Cox proportional hazards model. Logistic regression models were used to define odds ratios (ORs) for clinical benefit (CB). Landmark analysis and extended Cox models were used to mitigate lead-time bias by treating irAEs as a time-varying covariate.Results
Most patients (71.0%) were male, and one-third of patients (33.0%) experienced at least one irAE, most commonly involving the endocrine glands (13.0%), gastrointestinal tract (10.5%), or skin (10.0%). Patients who experienced irAEs had significantly longer OS (hazard ratio [HR], 0.52; p = .013), higher chance of CB (OR, 2.10; p = .023) and showed a trend toward longer PFS (HR, 0.71; p = .065) in multivariate analysis. Patients who had endocrine irAEs, particularly thyroid irAEs, had significantly longer OS and PFS and higher chance of CB. In a 14-week landmark analysis, irAEs were significantly associated with prolonged OS (p = .045). Patients who experienced irAEs had significantly longer median OS (44.5 vs. 18.2 months, p = .005) and PFS (7.5 vs. 3.6 months, p = .003) without landmark compared with patients who did not.Conclusion
We found that patients with mRCC treated with ICIs who experienced irAEs, particularly thyroid irAEs, had significantly improved clinical outcomes compared with patients who did not have irAEs. This suggests that irAEs may be effective clinical biomarkers in patients with mRCC treated with ICIs. Future prospective studies are warranted to validate these findings.Implications for Practice
This study found that early onset immune-related adverse events (irAEs) are associated with significantly improved clinical outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICIs). In this site-specific irAE analysis, endocrine irAEs, particularly thyroid irAEs, were significantly associated with improved clinical outcomes. These results have implications for practicing medical oncologists given the increasing use of ICIs for the treatment of mRCC. Importantly, these results suggest that early irAEs and thyroid irAEs at any time on treatment with ICIs may be clinical biomarkers of clinical outcomes in patients with mRCC treated with ICIs.18.
AimThe growing use of immune checkpoint inhibitors (ICIs) is associated with the occurrence of immune-related adverse events (irAEs). Few data are published on systemic, immunohaematological and rheumatic irAEs. In a pharmacovigilance database analysis, we screened for these irAEs and calculated their prevalence.Patients and methodsParticipants were recruited via Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie (REISAMIC)1 a French registry of grade ≥2 irAEs occurring in ICI-treated patients. The pathologies of interest were systemic autoimmune and inflammatory diseases, rheumatic diseases and immune cytopenia.ResultsOut of 908 patients treated with anti-Programmed cell Death 1 (PD1)/anti-Programmed cell Death-Ligand 1 (PD-L1) agents (together with an anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) agent in 40 cases) between December 2012 and December 2016 at a single centre, 21 patients experienced systemic irAEs. The types and the prevalence of irAEs were as follows: immune thrombocytopenia (0.2%), Sjögren syndrome (0.3%), rheumatoid arthritis (0.2%), polymyalgia rheumatica (0.2%), psoriatic arthritis (0.2%), seronegative polyarthritis (0.7%) and sarcoidosis (0.2%). Patients with Sjögren syndrome or seronegative polyarthritis were more likely to have received combination therapy with ipilimumab (2.5% for both).We described these 21 cases, together with nine additional cases from five other centres. Most irAE were moderately severe (grade 2, 63%). The median time to onset was 57°days (interquartile range (IQR) 24–117). The ICI was withdrawn in 12 cases, 25 patients (83%) received corticosteroids, and five patients (17%) received immunosuppressant/immunomodulatory agents. The irAEs resolved fully or partially in 28 cases (93%).ConclusionAlthough systemic, immunohaematological and rheumatic diseases are rarely associated with ICI use, the prevalence is higher when two ICIs are combined. Corticosteroids are often effective and may enable the continued administration of ICIs. Studies designed to identify at-risk patients are warranted. 相似文献
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近年来,免疫检查点抑制剂(ICI)在黑色素瘤治疗中取得了显著的成效,但是T细胞功能的活化也引起了一系列免疫相关不良反应(ir AE)。不同于传统化疗的不良反应,ir AE有着独特的临床表现和处理要求。虽然ir AE的发生和管理逐渐得到临床医生的重视,但一些常见ir AE的发生机制、临床表现、诊断和鉴别及其综合监测管理仍需进一步总结和归纳,以便提高临床医生工作水平和临床试验设计质量。而且不同ir AE的发生机制、糖皮质激素的治疗影响、原有自身免疫疾病患者的治疗风险等问题仍存在争议。本文阐述ICI治疗黑色素瘤引起的ir AE相关临床表现特点和诊疗管理措施,旨在对ir AE管理策略和研究方向提出具有指导意义的意见。 相似文献
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Pembrolizumab-Associated Cutaneous and Pulmonary Sarcoidosis in Non–Small Cell Lung Cancer Treatment
《Clinical lung cancer》2022,23(6):542-546
Immune checkpoint inhibitor (ICI) therapy has reshaped the treatment landscape in many cancers including non–small cell lung cancer (NSCLC). ICI-therapy can lead to a diverse array of immune-related adverse effects (irAEs), and prompt recognition and management are key to successful treatment. With wide-spread use of ICI therapy in clinical practice, rare irAEs are being increasingly recognized. This report documents a patient with advanced NSCLC who developed pembrolizumab-associated sarcoidosis with multiorgan involvement. Multidisciplinary management led to timely diagnosis and treatment, leading to improvement in symptoms. This case raises awareness of sarcoidosis as a rare side effect of pembrolizumab. 相似文献