For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
1
views
59
references
 Top references
cited by
12
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      255
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Management of Immune Checkpoint Inhibitor Toxicities

      review-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Immune checkpoint inhibitors (ICIs) have radically changed the clinical outcome of several cancers with durable responses. CTLA-4 (cytotoxic T lymphocyte antigen-4), PD-1 (programmed cell death protein 1) or PDL-1 (programmed cell death ligand protein 1) represent ICIs that can be used as monotherapy or in combination with other agents. The toxicity p\rofiles of ICIs differ from the side effects of cytotoxic agents and come with new toxicities like immune-related adverse events. Typically, these toxicities occur in all organs. However, the main organs affected are the skin, digestive, hepatic, lungs, rheumatologic, and endocrine. Most of the immune toxicity that occurs is low grade but some more severe toxicities can occur that require a rapid diagnosis and appropriate treatment. The recognition of symptoms by physicians and patient is necessary to resolve them rapidly and adapt treatment to allow the toxicity to resolve.

          Related collections

          Most cited references59

          • Record: found
          • Abstract: found
          • Article: not found

          Myocarditis in Patients Treated With Immune Checkpoint Inhibitors

          John D Groarke, Michael Fradley, Justine Cohen … (2018)
          BACKGROUND Myocarditis is an uncommon, but potentially fatal, toxicity of immune checkpoint inhibitors (ICI). Myocarditis after ICI has not been well characterized. OBJECTIVES The authors sought to understand the presentation and clinical course of ICI-associated myocarditis. METHODS After observation of sporadic ICI-associated myocarditis cases, the authors created a multicenter registry with 8 sites. From November 2013 to July 2017, there were 35 patients with ICI-associated myocarditis, who were compared to a random sample of 105 ICI-treated patients without myocarditis. Covariates of interest were extracted from medical records including the occurrence of major adverse cardiac events (MACE), defined as the composite of cardiovascular death, cardiogenic shock, cardiac arrest, and hemodynamically significant complete heart block. RESULTS The prevalence of myocarditis was 1.14% with a median time of onset of 34 days after starting ICI (inter-quartile range: 21 to 75 days). Cases were 65 ± 13 years of age, 29% were female, and 54% had no other immune-related side effects. Relative to controls, combination ICI (34% vs. 2%; p < 0.001) and diabetes (34% vs. 13%; p = 0.01) were more common in cases. Over 102 days (interquartile range: 62 to 214 days) of median follow-up, 16 (46%) developed MACE; 38% of MACE occurred with normal ejection fraction. There was a 4-fold increased risk of MACE with troponin T of ≥1.5 ng/ml (hazard ratio: 4.0; 95% confidence interval: 1.5 to 10.9; p = 0.003). Steroids were administered in 89%, and lower steroids doses were associated with higher residual troponin and higher MACE rates. CONCLUSIONS Myocarditis after ICI therapy may be more common than appreciated, occurs early after starting treatment, has a malignant course, and responds to higher steroid doses.
          Article 0 comments Cited 402 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small cell lung cancer

            L DeRosa, M D Hellmann, M Spaziano … (2018)
            Background The composition of gut microbiota affects antitumor immune responses, preclinical and clinical outcome following immune checkpoint inhibitors (ICI) in cancer. Antibiotics (ATB) alter gut microbiota diversity and composition leading to dysbiosis, which may affect effectiveness of ICI. Patients and methods We examined patients with advanced renal cell carcinoma (RCC) and non-small-cell lung cancer (NSCLC) treated with anti-programmed cell death ligand-1 mAb monotherapy or combination at two academic institutions. Those receiving ATB within 30 days of beginning ICI were compared with those who did not. Objective response, progression-free survival (PFS) determined by RECIST1.1 and overall survival (OS) were assessed. Results Sixteen of 121 (13%) RCC patients and 48 of 239 (20%) NSCLC patients received ATB. The most common ATB were β-lactam or quinolones for pneumonia or urinary tract infections. In RCC patients, ATB compared with no ATB was associated with increased risk of primary progressive disease (PD) (75% versus 22%, P  < 0.01), shorter PFS [median 1.9 versus 7.4 months, hazard ratio (HR) 3.1, 95% confidence interval (CI) 1.4–6.9, P  < 0.01], and shorter OS (median 17.3 versus 30.6 months, HR 3.5, 95% CI 1.1–10.8, P  = 0.03). In NSCLC patients, ATB was associated with similar rates of primary PD (52% versus 43%, P  = 0.26) but decreased PFS (median 1.9 versus 3.8 months, HR 1.5, 95% CI 1.0–2.2, P  = 0.03) and OS (median 7.9 versus 24.6 months, HR 4.4, 95% CI 2.6–7.7, P  < 0.01). In multivariate analyses, the impact of ATB remained significant for PFS in RCC and for OS in NSCLC. Conclusion ATB were associated with reduced clinical benefit from ICI in RCC and NSCLC. Modulatation of ATB-related dysbiosis and gut microbiota composition may be a strategy to improve clinical outcomes with ICI.
            Article 0 comments Cited 311 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Treatment-Related Adverse Events of PD-1 and PD-L1 Inhibitors in Clinical Trials

              Yucai Wang, Shouhao Zhou, Fang Yang … (2019)
              Programmed cell death (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have been increasingly used in cancer therapy. Understanding the treatment-related adverse events of these drugs is critical for clinical practice.
              Article 0 comments Cited 282 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Cancer Manag Res
                Journal ID (iso-abbrev): Cancer Manag Res
                Journal ID (publisher-id): cmar
                Journal ID (pmc): cancmanres
                Title: Cancer Management and Research
                Publisher: Dove
                ISSN (Electronic): 1179-1322
                Publication date (Electronic): 28 September 2020
                Publication date Collection: 2020
                Volume: 12
                Pages: 9139-9158
                Affiliations
                [1 ]Department of Medical Oncology, Hôpital Saint-André, CHU Bordeaux-University of Bordeaux , Bordeaux, France
                [2 ]ImmunoConcEpt, CNRS UMR 5164, Bordeaux University , Bordeaux 33076, France
                Author notes
                Correspondence: Amaury Daste Department of Medical Oncology, Hôpital Saint-André, CHU Bordeaux-University of Bordeaux , 1 Rue Jean Burguet, Bordeaux33000, FranceFax +33 5 56 79 58 96 Email amaury.daste@chu-bordeaux.fr
                Author information
                http://orcid.org/0000-0001-9139-8103
                http://orcid.org/0000-0001-9455-6744
                Article
                Publisher ID: 218756
                DOI: 10.2147/CMAR.S218756
                PMC ID: 7533913
                PubMed ID: 33061607
                SO-VID: e27d5b68-c8ed-4ee1-8f04-0099a880692d
                Copyright © © 2020 Durrechou et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 15 May 2020
                Date accepted : 07 August 2020
                Page count
                Figures: 4, Tables: 3, References: 103, Pages: 20
                Funding
                Funded by: No funding;
                No funding for this review.
                Categories
                Subject: Review

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: immune check point inhibitor,toxicity,corticosteroids,immunosuppressive treatments
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: immune check point inhibitor, toxicity, corticosteroids, immunosuppressive treatments

                Comments

                Comment on this article

                scite_

                Similar content255

                See all similar

                Cited by12

                See all cited by

                Most referenced authors2,437

                See all reference authors