Development of red blood cell autoantibodies following treatment with checkpoint inhibitors: a new class of anti-neoplastic, immunotherapeutic agents associated with immune dysregulation

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Immunohematology

American National Red Cross

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ISSN: 0894-203X
eISSN: 1930-3955

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VOLUME 33 , ISSUE 1 (March 2017) > List of articles

Development of red blood cell autoantibodies following treatment with checkpoint inhibitors: a new class of anti-neoplastic, immunotherapeutic agents associated with immune dysregulation

Laura L.W. Cooling * / John Sherbeck / Jonathon C. Mowers / Sheri L. Hugan

Keywords : checkpoint inhibitor, autoantibody, anemia, cytopenia

Citation Information : Immunohematology. Volume 33, Issue 1, Pages 15-21, DOI: https://doi.org/10.21307/immunohematology-2019-004

License : (Transfer of Copyright)

Published Online: 09-October-2019

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ABSTRACT

Ipilimumab, nivolumab, and pembrolizumab represent a new class of immunotherapeutic drugs for treating patients with advanced cancer. Known as checkpoint inhibitors, these drugs act to upregulate the cellular and humoral immune response to tumor antigens by inhibiting T-cell autoregulation. As a consequence, they can be associated with immune-related adverse events (irAEs) due to loss of self-tolerance, including rare cases of immune-related cytopenias. We performed a retrospective clinical chart review, including serologic, hematology, and chemistry laboratory results, of two patients who developed red blood cell (RBC) autoantibodies during treatment with a checkpoint inhibitor. Serologic testing of blood samples from these patients during induction therapy with ipilimumab and nivolumab, respectively, showed their RBCs to be positive by the direct antiglobulin test (IgG+, C3+) and their plasma to contain panreactive RBC autoantibodies. Neither patient had evidence of hemolysis. Both patients developed an additional irAE during treatment. A literature review for patients who had developed immune-mediated cytopenia following treatment with a checkpoint inhibitor was performed. Nine other patients were reported with a hematologic irAE, including six with anemia attributable to autoimmune anemia, aplastic anemia, or pure RBC aplasia. Hematologic irAEs tend to occur early during induction therapy, often coincident with irAEs of other organs. In conclusion, checkpoint inhibitors can be associated with the development of autoantibodies, immune-mediated cytopenias, pure RBC aplasia, and aplastic anemia. Immunohematology reference laboratories should be aware of these agents when evaluating patients with advanced cancer and new-onset autoantibodies, anemia, and other cytopenias.

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REFERENCES

1. Tarhini A. Immune-mediated adverse events associated with ipilimumab CTLA-4 blockade therapy: the underlying mechanisms and clinical management. Scientifica 2013: Article ID 857519. dx.doi.org/10.1155/2013/857519.

2. Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010;363:711–23.

3. Gao J, He Q, Subudhi S, et al. Review of immune-related adverse events in prostate cancer patients treated with ipilimumab: MD Anderson experience. Oncogene 2015;34:5411–7.

4. Davids MS, Kim HT, Bachireddy P, et al. Ipilimumab for patients with relapse after allogeneic transplantation. N Engl J Med 2016;375:143–53.

5. Mahoney KM, Freeman GJ, McDermott DF. The next immunecheckpoint inhibitors: PD-1/PD-L1 blockade in melanoma. Clin Ther 2015;37:764–82.

6. Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012;366:2443–54.

7. Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 2015;372:2018–20.

8. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small cell lung cancer. N Engl J Med 2015;373:123–35.

9. National Institutes of Health, Clinical Trials Web site. Available at https://ClinicalTrials.gov/. Last accessed 8/29/2016.

10. Li S, Chen S, Yang L, Li Y. The role of PD-1 and PD-L1 in T-cell immune suppression in patients with hematological malignancies. J Hematol Oncol 2013;6:74. 

11. Gibson R, Delaune J, Szady A, Markham M. Suspected autoimmune myocarditis and cardiac conduction abnormalities with nivolumab therapy for non-small cell lung cancer. BMJ Case Rep 2016. doi:10.1136/bcr-2016-216228.

12. Du Rusquec P, Saint-Jean M, Brocard A, et al. Ipilimumabinduced autoimmune pancytopenia in a case of metastatic melanoma. J Immunother 2014;37:348–50.

13. Gordon IO, Wade T, Chin K, Dickstein J, Gajewski TF. Immunemediated red cell aplasia after anti-CTLA-4 immunotherapy for metastatic melanoma. Cancer Immunol Immunother 2009;58:1351–3.

14. Simeone E, Grimaldi AM, Esposito A, et al. Serious haematological toxicity during and after ipilimumab treatment: a case series. J Med Case Rep 2014;8:240.

15. Kong BY, Micklethwaite KP, Swaminathan S, Kefford RF, Carlino MS. Autoimmune hemolytic anemia induced by anti-PD-1 therapy in metastatic melanoma. Melanoma Res 2016;26:202–4.

16. Nair R, Gheith S, Nair SG. Immunotherapy-associated hemolytic anemia with pure red cell aplasia. N Engl J Med 2016;374:1096–7.

17. Judd WJ, Johnson ST, Storry JR. Judd’s methods in immunohematology. 3rd ed. Bethesda, MD: American Association of Blood Banks, 2008.

18. Weldy L. Polyethylene glycol antiglobulin test (PEG-AGT). Immunohematology 2014:30:158–60.

19. Cappelli LC, Gutierrez AK, Baer AN, et al. Inflammatory arthritis and sicca syndrome induced by nivolumab and ipilimumab. Ann Rheum Dis 2017;76:43–50.

20. Sun J, Schiffman J, Raghunath A, Ng Tang D, Chen H, Sharma P. Concurrent decrease in IL-10 with development of immunerelated adverse events in a patient treated with anti-CTLA-4 therapy. Cancer Immun 2008;8:9.

21. Von Euw E, Chodon T, Attar N, et al. CTLA4 blockade increases Th17 cells in patients with metastatic melanoma. J Transl Med 2009;7:35.

22. Ahmad E, Elgohary T, Ibrahim H. Naturally occurring regulatory T cells and interleukins 10 and 12 in the pathogenesis of idiopathic warm autoimmune hemolytic anemia. J Investig Allergol Clin Immunol 2011;21:297–304.

23. Mqadmi A, Zheng X, Yazdanbakhsh K. CD4+CD25+ regulatory T cells control induction of autoimmune hemolytic anemia. Blood 2005;105:3746–8.

24. Ward FJ, Hall AM, Cairns LS, et al. Clonal regulatory T cells specific for a red blood cell autoantigen in human autoimmune hemolytic anemia. Blood 2008;111:680–7.

 

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