Association Between RBC Antigen Allo-Antibodies and Immune-Related Adverse Events During Immune Checkpoint Inhibitor Treatment for Advanced Cancers

Natasha A Jain; Songzhu Zhao; Lai Wei; Kerry A Rogers; Gregory A Otterson; Tzu-Fei Wang; Dwight H Owen

doi:10.2147/CMAR.S264166

Association Between RBC Antigen Allo-Antibodies and Immune-Related Adverse Events During Immune Checkpoint Inhibitor Treatment for Advanced Cancers

Cancer Manag Res. 2020 Nov 17:12:11743-11749. doi: 10.2147/CMAR.S264166. eCollection 2020.

Authors

Natasha A Jain^{1

2}, Songzhu Zhao³, Lai Wei³, Kerry A Rogers^{1

2}, Gregory A Otterson¹, Tzu-Fei Wang², Dwight H Owen¹

Affiliations

¹ Division of Medical Oncology, The Ohio State University, Columbus, OH, USA.
² Division of Hematology, The Ohio State University, Columbus, OH, USA.
³ Center for Biostatistics, The Ohio State University, Columbus, OH, USA.

Abstract

Introduction: Immune checkpoint inhibitors (ICI) have become a primary treatment modality for patients with a variety of malignancies. Given their increasing use, it is essential to be familiar with their immune-related adverse events (irAEs). Here we report a severe case of autoimmune hemolytic anemia (AIHA) associated with cold agglutinin precipitated by pembrolizumab, and a retrospective study of patients treated with ICI utilizing an institutional database where we analyzed the patterns of anti-RBC testing and their ability to predict irAE.

Methods: Patients treated with at least one dose of ICI (PD-1, PD-L1, CTLA-4 inhibitors) for advanced cancer between November 2012 and September 2017 at our institution were included. Electronic Medical Records were reviewed to abstract data. Medians and 95% CIs were estimated using Kaplan-Meier method and differences compared using the Log Rank test. Fisher's exact test and Chi square test were used to analyze clinical associations.

Results: We identified 1065 patients who received at least one dose of ICI: 180/1065 (17%) underwent direct antiglobulin test (DAT) or allo-antibody (alloAb) testing at any time; 127/1065 (12%) had either DAT or alloAb testing pre-ICI; 129 had either DAT or alloAb testing after ICI initiation; and 76 had either DAT or alloAb testing at both time points. There was a significant association between positive alloAb pre-ICI and the development of irAE while on ICI (p = 0.04).

Conclusion: Given the increasing use of ICI, oncologists should be aware of potential irAEs with ICI. We found an association between the presence of an alloAb pre-ICI and the development of irAE, indicating that this previous non-self antigen response may predict immune adverse events. A larger prospective study is needed for systematic evaluation of the association between alloAb testing and irAE, and whether routine testing may inform clinical decision-making for patients.

Keywords: autoimmune hemolytic anemia; direct antiglobulin test; immune checkpoint inhibitors; immune-related adverse events; immunotherapy; red blood cell allo-antibodies.

Grants and funding

Research reported in this publication was supported in part by the Ohio State University Comprehensive Cancer Center and the National Institutes of Health under grant number P30 CA016058. Dr. Owen is supported by a Paul Calabresi Career Development Award for Clinical Oncology K12CA133250. Dr. Rogers is a Scholar in Clinical Research of The Leukemia & Lymphoma Society (CDP 2331-20).