Retrospective Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Feb 24, 2021; 12(2): 103-114
Published online Feb 24, 2021. doi: 10.5306/wjco.v12.i2.103
Racial disparities in immune-related adverse events of immune checkpoint inhibitors and association with survival based on clinical and biochemical responses
Monica Peravali, Cristiane Gomes-Lima, Eshetu Tefera, Mairead Baker, Mamta Sherchan, Saira Farid, Kenneth Burman, Florina Constantinescu, Irina Veytsman
Monica Peravali, Irina Veytsman, Department of Hematology/Oncology, MedStar Washington Hospital Center, Washington, DC 20010, United States
Cristiane Gomes-Lima, Kenneth Burman, Department of Endocrinology, MedStar Washington Hospital Center, Washington, DC 20010, United States
Eshetu Tefera, Department of Biostatistics and Bioinformatics, MedStar Health Research Institute, Washington, DC 20010, United States
Mairead Baker, Saira Farid, Department of Internal Medicine, MedStar Washington Hospital Center, Washington, DC 20010, United States
Mamta Sherchan, Florina Constantinescu, Department of Rheumatology, MedStar Washington Hospital Center, Washington, DC 20010, United States
Author contributions: Peravali M, Gomes-Lima C, Burman K, Constantinescu F, and Veytsman I designed the research study; Peravali M, Gomes-Lima C, Baker M, Sherchan M, Farid S, and Veytsman I collected data for research; Tefera E provided biostatistics and analysis of data; Peravali M, Gomes-Lima C, Burman K, Tefera E, and Veytsman I wrote and revised the manuscript; all authors have read and approved the final manuscript.
Institutional review board statement: This study was reviewed and approved by the MedStar Health Research Institute Ethics Committee. Approved IRB code STUDY00001266.
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Monica Peravali, MD, Academic Fellow, Department of Hematology/ Oncology, MedStar Washington Hospital Center, 110 Irving Street, Washington, DC 20010, United States. monica.peravali@medstar.net
Received: December 14, 2020
Peer-review started: December 14, 2020
First decision: December 24, 2020
Revised: January 4, 2021
Accepted: January 21, 2021
Article in press: January 21, 2021
Published online: February 24, 2021
Processing time: 69 Days and 21.1 Hours
Abstract
BACKGROUND

Immune checkpoint inhibitors (ICPi) cause various immune-related adverse events (irAE) with thyroid dysfunction as a commonly reported abnormality. There is increasing evidence showing positive association with development of irAE and survival. However, prior trials with ICPi had underrepresentation of minorities with < 5% African Americans.

AIM

To evaluate the association between development of irAE and survival outcomes among a racially diverse patient population.

METHODS

Data on patients with stage IV solid malignancies treated with programmed cell death-protein 1/programmed death ligand 1 blockers between January 2013 and December 2018 across MedStar Georgetown Cancer Institute facilities were retrospectively reviewed. Patients treated with cytotoxic T-lymphocyte-associated protein 4 inhibitors were excluded. Progression free survival (PFS) and overall survival (OS) were primary endpoints and were calculated using Kaplan-Meier methods and Wilcoxon rank sum test for comparison.

RESULTS

Out of 293 patients who met eligibility criteria, 91 pts (31%) had any grade irAE; most common AE were endocrine (40.7%) specifically TSH elevation, dermatological (23.1%) and rheumatologic (18.7%). Proportion of irAE was significantly higher in Caucasians vs African Americans (60.4% vs 30.8%), in patients with low programmed death ligand 1, lower LDH, older age, and those who had more treatment cycles with ICPi. Rate of progression was lower in patients with irAE (30.8% vs 46.0%, P = 0.0140). Median PFS (5.8 vs 3.0 mo, P = 0.0204) and OS (17.1 vs 7.2 mo, P < 0.0001) were higher with irAE. Statistically significant difference in OS (17.1 vs 8.6 mo, P = 0.0002) but not in PFS (5.8 vs 3.3 mo, P = 0.0545) was noted with endocrine irAE. No differences in survival were observed among other commonly reported irAE. Differences in survival among subgroups of patients with irAE are described.

CONCLUSION

Development of irAE positively correlated with improved PFS and OS as reported in previous studies. To our knowledge, this is the first study observing differences in OS favoring endocrine AE and Caucasian race. These factors may be potential surrogate markers of prognosis pending replication of these results in large-scale studies.

Keywords: Immunotherapy; Adverse events; Endocrine; Survival; Race; Minority

Core Tip: Immune checkpoint inhibitors have revolutionized the treatment of many types of cancer, yet they cause various immune-related adverse events (irAEs), notably thyroid dysfunction. Development of irAEs has been reported as a surrogate marker of improved survival. However, minority racial group representation is a limitation in immunotherapy trials. In this retrospective study, we evaluate the association of development of irAEs to survival outcomes in patients treated with immune checkpoint inhibitors for advanced stage solid malignancies. The racial diversity of the population of patients is a unique feature of this study. Our data concluded a positive correlation of irAEs development with increased probability of survival and demonstrates a positive correlation with Caucasian race and overall survival.