Reviews
2 January 2018

Use of Immune Checkpoint Inhibitors in the Treatment of Patients With Cancer and Preexisting Autoimmune Disease: A Systematic Review

Publication: Annals of Internal Medicine
Volume 168, Number 2

Abstract

Background:

Cancer immunotherapy with checkpoint inhibitors (CPIs) is associated with frequent immune-related adverse events (irAEs) and is often not recommended for patients with concomitant autoimmune disease.

Purpose:

To summarize the evidence on adverse events associated with CPIs in patients with cancer and preexisting autoimmune disease.

Data Sources:

MEDLINE, EMBASE, Web of Science, PubMed ePubs, and the Cochrane Central Register of Controlled Trials through September 2017 with no language restrictions.

Study Selection:

Original case reports, case series, and observational studies describing patients with cancer and autoimmune disease who were receiving CPIs.

Data Extraction:

2 reviewers independently extracted data and assessed the quality of reporting.

Data Synthesis:

123 patients in 49 publications were identified; 92 (75%) had exacerbation of preexisting autoimmune disease, irAEs, or both. No differences in adverse events were observed in patients with active versus inactive disease. Patients receiving immunosuppressive therapy at initiation of CPI therapy seemed to have fewer adverse events than those not receiving treatment. Most flares and irAEs were managed with corticosteroids; 16% required other immunosuppressive therapies. Adverse events improved in more than half of patients without discontinuation of CPI therapy. Three patients died of adverse events.

Limitations:

The quality and quantity of data were limited. Case reports typically describe unique manifestations and are not generalizable to the population at large. Because there were no prospective observational studies, incidence could not be determined.

Conclusion:

Flares and irAEs in patients with autoimmune disease who are receiving CPIs can often be managed without discontinuing therapy, although some events may be severe and fatal. Prospective longitudinal studies are needed to establish incidence of adverse events and evaluate risk–benefit ratios and patient preferences in this population.

Primary Funding Source:

National Institute of Arthritis and Musculoskeletal and Skin Diseases.

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Supplemental Material

Supplement 1. Research Protocol

Supplement 2. Supplementary Material

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Information & Authors

Information

Published In

cover image Annals of Internal Medicine
Annals of Internal Medicine
Volume 168Number 216 January 2018
Pages: 121 - 130

History

Published online: 2 January 2018
Published in issue: 16 January 2018

Keywords

Authors

Affiliations

Noha Abdel-Wahab, MD, PhD
University of Texas MD Anderson Cancer Center, Houston, Texas, and Assiut University Hospitals, Assiut, Egypt (N.A.)
Mohsin Shah, MD
University of Texas MD Anderson Cancer Center, Houston, Texas (M.S., M.A.L., M.E.S.)
Maria A. Lopez-Olivo, MD, PhD
University of Texas MD Anderson Cancer Center, Houston, Texas (M.S., M.A.L., M.E.S.)
Maria E. Suarez-Almazor, MD, PhD
University of Texas MD Anderson Cancer Center, Houston, Texas (M.S., M.A.L., M.E.S.)
Note: Dr. Suarez-Almazor had full access to all of the data in the study and takes responsibility for the integrity and accuracy of the data analysis.
Acknowledgment: The authors thank Gregory F. Pratt from the Research Medical Library at The University of Texas MD Anderson Cancer Center for assisting with data acquisition.
Grant Support: Dr. Suarez-Almazor had a K24 career award from the National Institute of Arthritis and Musculoskeletal and Skin Diseases while the study was conducted (grant AR053593).
Disclosures: Dr. Lopez-Olivo reports an Investigator Award from the Rheumatology Research Foundation outside the submitted work. Dr. Suarez-Almazor reports consultant fees from Bristol-Myers Squibb outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-2073.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement: Study protocol: See Supplement 1. Statistical code: Not applicable. Data set: See the tables in Supplement 2 and the Appendix Figure.
Corresponding Author: Maria E. Suarez-Almazor, MD, PhD, Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, Unit 1465, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030; e-mail, [email protected].
Current Author Addresses: Dr. Abdel-Wahab: Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, Unit 1465, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, and Department of Rheumatology and Rehabilitation, Assiut University Hospitals, Assiut Faculty of Medicine, Egypt.
Drs. Shah, Lopez-Olivo, and Suarez-Almazor: Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, Unit 1465, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030
Author Contributions: Conception and design: N. Abdel-Wahab, M.E. Suarez-Almazor.
Analysis and interpretation of the data: N. Abdel-Wahab, M. Shah, M.E. Suarez-Almazor.
Drafting of the article: N. Abdel-Wahab, M. Shah, M.E. Suarez-Almazor.
Critical revision of the article for important intellectual content: N. Abdel-Wahab, M. Shah, M.A. Lopez-Olivo, M.E. Suarez-Almazor.
Final approval of the article: N. Abdel-Wahab, M. Shah, M.A. Lopez-Olivo, M.E. Suarez-Almazor.
Statistical expertise: N. Abdel-Wahab, M. Shah.
Obtaining of funding: M.E. Suarez-Almazor.
Administrative, technical, or logistic support: M.E. Suarez-Almazor.
Collection and assembly of data: N. Abdel-Wahab, M. Shah, M.A. Lopez-Olivo.
This article was published at Annals.org on 2 January 2018.

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Noha Abdel-Wahab, Mohsin Shah, Maria A. Lopez-Olivo, et al. Use of Immune Checkpoint Inhibitors in the Treatment of Patients With Cancer and Preexisting Autoimmune Disease: A Systematic Review. Ann Intern Med.2018;168:121-130. [Epub 2 January 2018]. doi:10.7326/M17-2073

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