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

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

Natasha A Jain  1   2 , Songzhu Zhao  3 , Lai Wei  3 , Kerry A Rogers  1   2 , Gregory A Otterson  1 , Tzu-Fei Wang  2 , Dwight H Owen  1
Affiliations

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

Natasha A Jain et al. Cancer Manag Res. .

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.

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Conflict of interest statement

Kerry Rogers reports grants from Genetech, AbbVie, and Janssen and personal fees from Acerta Pharma, AstraZeneca, and Pharmacyclics, during the conduct of the study. Dwight Owen reports grants from Palobiofarma, BMS, Merck, and Genentech and personal fees from theMednet.org and AstraZeneca, outside the submitted work. The authors report no other potential conflicts of interest for this work.

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