Thu0628 immune-Related Adverse Events Induced by Cancer Immunotherapies. Big Data Analysis of 13,051 Cases (Immunocancer International Registry)

Ramos‐Casals, Manuel; Lambotte, O.; Kostine, Marie; Calabrese, Leonard H.; Suarez‐Almazor, María E.; Bingham, Clifton O.; Baldini, Chiara; Schaeverbeke, Thierry; Gottenberg, Jacques-Éric; Schulze‐Koops, Hendrik; Leipe, Jan; Calabrese, Cassandra; Brito-Zerón, Pilar; Flores-Chávez, Alejandra; Kostov, Belchin; Retamozo, Soledad; Citera, Gustavo; Aguilar, Eva; Richter, Michael; Lidar, Merav; Fisher, Benjamin A; Michot, Jean‐Marie; Liew, David; Buchanan, Russell; Schrumpf-Heiberg, Marte; Guilpain, Philippe; Danda, Debashish; Olsson, Peter; Suzuki, Yasunori; Kılıçkap, Saadettin; Hernández-Molina, Gabriela; Trevisani, Virgínia Fernandes Moça; Praprotnik, Sonja; Horváth, Ildikó; Azuma, Naoto; Armağan, Berkan; Khamashta, Munther A.; Mariette, Xavier

doi:10.1136/annrheumdis-2019-eular.2707

Cited by 12 publications

(10 citation statements)

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“…Immune checkpoint inhibitors (ICPI) may also lead to a multitude of endocrinopathies, such as thyroiditis, primary adrenal insufficiency, diabetes mellitus, and hypophysitis [4,5]. Notably, hypophysitis is a frequent irAE [6][7][8], occurring in 5% of ICPI-treated patients according to a recent big data analysis [9].…”

Section: Introductionmentioning

confidence: 99%

Differences between immunotherapy-induced and primary hypophysitis—a multicenter retrospective study

et al. 2021

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Objective Immune checkpoint inhibitors can cause various immune-related adverse events including secondary hypophysitis. We compared clinical characteristics of immunotherapy-induced hypophysitis (IIH) and primary hypophysitis (PH) Design Retrospective multicenter cohort study including 56 patients with IIH and 60 patients with PH. Methods All patients underwent extensive endocrine testing. Data on age, gender, symptoms, endocrine dysfunction, MRI, immunotherapeutic agents and autoimmune diseases were collected. Results Median time of follow-up was 18 months in IIH and 69 months in PH. The median time from initiation of immunotherapy to IIH diagnosis was 3 months. IIH affected males more frequently than PH (p < 0.001) and led to more impaired pituitary axes in males (p < 0.001). The distribution of deficient adenohypophysial axes was comparable between both entities, however, central hypocortisolism was more frequent (p < 0.001) and diabetes insipidus considerably less frequent in IIH (p < 0.001). Symptoms were similar except that visual impairment occurred more rarely in IIH (p < 0.001). 20 % of IIH patients reported no symptoms at all. Regarding MRI, pituitary stalk thickening was less frequent in IIH (p = 0.009). Concomitant autoimmune diseases were more prevalent in PH patients before the diagnosis of hypophysitis (p = 0.003) and more frequent in IIH during follow-up (p = 0.002). Conclusions Clinically, IIH and PH present with similar symptoms. Diabetes insipidus very rarely occurs in IIH. Central hypocortisolism, in contrast, is a typical feature of IIH. Preexisting autoimmunity seems not to be indicative of developing IIH.

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Section: Introductionmentioning

confidence: 99%

Differences between immunotherapy-induced and primary hypophysitis—a multicenter retrospective study

et al. 2021

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“…However, some reports have found irAEs within days or even years of treatment initiation. With this recent explosion of ICIs, the incidence of irAEs has had a similarly rapid rise with a recorded 13,000 irAE cases in 2018 ( 13 ). Of these, 60% were associated with the three following agents: iplimumab, nivolumab and pembrolizumab ( 13 ).…”

Section: Epidemiologymentioning

confidence: 99%

“…With this recent explosion of ICIs, the incidence of irAEs has had a similarly rapid rise with a recorded 13,000 irAE cases in 2018 ( 13 ). Of these, 60% were associated with the three following agents: iplimumab, nivolumab and pembrolizumab ( 13 ). Figure 2 ( 2 , 14 ) displays the percent incidence of irAEs amongst trial populations based on ICI class (dual and monotherapies) from data collected through 9 melanoma clinical trials ( 14 ).…”

Section: Epidemiologymentioning

confidence: 99%

Advances in Knowledge and Management of Immune-Related Adverse Events in Cancer Immunotherapy

et al. 2022

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Immune-oncologic (IO) therapy has revolutionized the treatment and management of oncologic disease. Immunotherapy functions by enhancing the host immune-systems ability to endogenously clear malignant cells, however, this activation can also lead to immune-mediated damage to healthy native tissues. These side effects are known as immune-related adverse events or irAEs and can even present with phenotypes similar to autoimmune diseases. IrAEs are the major consequence of checkpoint inhibitors and can have a significant impact on a patient’s cancer treatment and long-term quality of life. The management of these irAEs follows a similar approach to autoimmune diseases. More specifically, the management is akin to that of autoimmune disease exacerbations. While there is an array of immune-suppressing agents that can be used, steroids, immunomodulators and IO discontinuation are cornerstones of irAE management. The exact approach and dosing are based on the severity and subtype of irAE presented. Within recent years, there has been a push to better prevent and manage irAEs when they arise. There has been an additional effort to increase the number of steroid-sparing agents available for irAE treatment given the consequences of long-term steroid therapy as well as patient contraindications to steroids. The goals of this review are to summarize irAE management, highlight significant advances made in recent years and emphasize the future directions that will optimize the use of IO therapy in oncology.

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“…The ImmunoCancer International Registry, which is a data-sharing multidisciplinary network from 18 countries focused on immune-related adverse events (irAE), has shown an accumulated annual number of nearly 13 000 irAE cases reported in 2018 and it has been increasing exponentially due to new indications of ICI alone or in combination with other agents, as well as increasing use of these therapies globally [ 6 ]. Therefore, attention to the impact of irAEs on patient safety and success of the treatment is essential.…”

Section: Clinical Implications Of Aes In Ici Therapy Of Cancermentioning

confidence: 99%

Balancing the good and the bad: controlling immune-related adverse events versus anti-tumor responses in cancer patients treated with immune checkpoint inhibitors

Evangelista

Figueiredo

Barros

et al. 2022

Immunotherapy Advances

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Immune checkpoint inhibitors (ICI) have provided new hope for cancer patients, and in particular for patients with tumors that are immunologically active and classified as hot tumors. These tumors express antigenic and tumor microenvironment (TME) characteristics that make them potential candidates for therapy with checkpoint inhibitors that aim to reactivate the immune response such as anti-PD-1 and anti-CTLA-4. Examples of potentially responsive cancers are, melanoma, non-small cell lung cancer and several other metastatic or unresectable tumors with genetic instability: DNA mismatch repair deficiency (dMMR), microsatellite instability-high (MSI-H), or with a high tumor mutational burden (TMB). Immunotherapy using checkpoint inhibitors is typically associated with adverse events (AEs) that are milder than those with chemotherapy. However, a significant percentage of patients develop short-term immune-related AEs (irAEs) which range from mild (~70%) to severe cases (~13%) that can lead to modifications of the checkpoint inhibitor therapy and in some cases, death. While some studies have investigated immune mechanisms behind the development of irAEs, much more research is needed to understand the mechanisms and to develop interventions that could attenuate severe irAEs, while maintaining the anti-tumor response intact. Moreover, studies to identify biomarkers that can predict the likelihood of a patient developing severe irAEs would be of great clinical importance. Here we discuss some of the clinical ramifications of irAEs, potential immune mechanisms behind their development and studies that have investigated potentially useful biomarkers of irAEs development.

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Thu0628 immune-Related Adverse Events Induced by Cancer Immunotherapies. Big Data Analysis of 13,051 Cases (Immunocancer International Registry)

Cited by 12 publications

References 0 publications

Differences between immunotherapy-induced and primary hypophysitis—a multicenter retrospective study

Differences between immunotherapy-induced and primary hypophysitis—a multicenter retrospective study

Advances in Knowledge and Management of Immune-Related Adverse Events in Cancer Immunotherapy

Balancing the good and the bad: controlling immune-related adverse events versus anti-tumor responses in cancer patients treated with immune checkpoint inhibitors

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