Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors

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Abstract

Immune checkpoint inhibitors (ICIs) are now a mainstay of cancer treatment. Although rare, fulminant and fatal toxic effects may complicate these otherwise transformative therapies; characterizing these events requires integration of global data.

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Most cited references 7

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Reduced mortality after allogeneic hematopoietic-cell transplantation.

Ted Gooley, Jason Chien, Steven A Pergam … (2010)

Over the past decade, advances have been made in the care of patients undergoing transplantation. We conducted a study to determine whether these advances have improved the outcomes of transplantation. We analyzed overall mortality, mortality not preceded by relapse, recurrent malignant conditions, and the frequency and severity of major complications of transplantation, including graft-versus-host disease (GVHD) and hepatic, renal, pulmonary, and infectious complications, among 1418 patients who received their first allogeneic transplants at our center in Seattle in the period from 1993 through 1997 and among 1148 patients who received their first allogeneic transplants in the period from 2003 through 2007. Components of the Pretransplant Assessment of Mortality (PAM) score were used in regression models to adjust for the severity of illness at the time of transplantation. In the 2003-2007 period, as compared with the 1993-1997 period, we observed significant decreases in mortality not preceded by relapse, both at day 200 (by 60%) and overall (by 52%), the rate of relapse or progression of a malignant condition (by 21%), and overall mortality (by 41%), after adjustment for components of the PAM score. The results were similar when the analyses were limited to patients who received myeloablative conditioning therapy. We also found significant decreases in the risk of severe GVHD; disease caused by viral, bacterial, and fungal infections; and damage to the liver, kidneys, and lungs. We found a substantial reduction in the hazard of death related to allogeneic hematopoietic-cell transplantation, as well as increased long-term survival, over the past decade. Improved outcomes appear to be related to reductions in organ damage, infection, and severe acute GVHD. (Funded by the National Institutes of Health.).

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Randomized, Double-Blind, Phase III Trial of Ipilimumab Versus Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic Chemotherapy-Naive Castration-Resistant Prostate Cancer

Tomasz M. Beer, Eugene Kwon, Charles Drake … (2017)

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VigiBase, the WHO Global ICSR Database System: Basic Facts

Marie Lindquist (2008)

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Author and article information

Journal

Title: JAMA Oncology

Abbreviated Title: JAMA Oncol

Publisher: American Medical Association (AMA)

ISSN (Print): 2374-2437

Publication date Created: December 01 2018

Publication date (Print): December 01 2018

Volume: 4

Issue: 12

Page: 1721

Affiliations

[1 ]Vanderbilt Ingram Cancer Center, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee

[2 ]Department of Pharmacology, Pharmacovigilance Unit, AP-HP, Pitié-Salpêtrière Hospital, Paris, France

[3 ]INSERM, UMR ICAN 1166, Sorbonne Universités, UPMC Univ Paris 06, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France

[4 ]Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts

[5 ]Robert H. Lurie Cancer Center, Department of Medicine, Northwestern University Medical Center, Chicago, Illinois

[6 ]National Center for Tumor Diseases, Department of Dermatology, University Hospital Heidelberg, Heidelberg, Germany

[7 ]Vanderbilt Ingram Cancer Center, Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee

[8 ]Melanoma Institute of Australia, Sydney, New South Wales, Australia

[9 ]University of Sydney, Sydney, New South Wales, Australia

[10 ]Royal North Shore Hospital, Sydney, New South Wales, Australia

[11 ]Mater Hospital, Sydney, New South Wales, Australia

[12 ]Department of Medical Oncology, Westmeade Hospital, Sydney, New South Wales, Australia

[13 ]Department of Medical Oncology, Blacktown Hospital, Sydney, New South Wales, Australia

[14 ]Department of Cutaneous Oncology, The Moffitt Cancer Center and Research Institute, Tampa, Florida

Article

DOI: 10.1001/jamaoncol.2018.3923

PMC ID: 6440712

PubMed ID: 30242316

SO-VID: 5f6a8954-1905-4096-a24d-e079ee5f364c

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Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors : A Systematic Review and Meta-analysis

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Abstract

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HLA-G and immune tolerance in pregnancy

Most cited references 7

Reduced mortality after allogeneic hematopoietic-cell transplantation.

Randomized, Double-Blind, Phase III Trial of Ipilimumab Versus Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic Chemotherapy-Naive Castration-Resistant Prostate Cancer

VigiBase, the WHO Global ICSR Database System: Basic Facts

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