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Medical Science Monitor Basic Research


Pembrolizumab-Induced Cold Agglutinin Disease

Unusual clinical course, Challenging differential diagnosis, Unusual or unexpected effect of treatment, Adverse events of drug therapy , Clinical situation which can not be reproduced for ethical reasons

Osman Atiq, Saad O. Atiq, Zainab O. Atiq, Vijay Patel, Mohammad O. Atiq, Omar T. Atiq

USA Department of Internal Medicine, Unity Health, Searcy, AR, USA

Am J Case Rep 2020; 21:e924283

DOI: 10.12659/AJCR.924283

Available online: 2020-07-31

Published: 2020-09-05


BACKGROUND: The introduction of immunotherapy in the management of metastatic lung cancer appears to be changing their natural history. Most patients tolerate immunotherapy without any significant adverse events. Nevertheless, a significant number of patients still experience adverse effects. Autoimmune hemolytic anemia has been described as mostly related to warm autoantibodies. The following case report describes cold agglutinin disease with hemolysis secondary to Pembrolizumab therapy for the treatment of metastatic lung cancer.
CASE REPORT: A 58-year-old woman noted a left neck mass 4 months prior to her presentation. A biopsy confirmed the presence of metastatic adenocarcinoma, consistent with primary lung cancer. Further evaluation revealed the tumor to be PDL-1-positive. She was started on Pembrolizumab, Pemetrexed, and carboplatin chemotherapy regimen. Her CBC was within normal limits when she started therapy, but within 4 weeks hemoglobin dropped to 4.3 g/dL. Further evaluation showed high cryoglobulin levels and a high cold agglutinin titer. Complement C3 DAT was positive. A peripheral smear showed clumps of red cells and the serum IgM was elevated. The diagnosis of CAD was made. She was then started on Rituximab. Imaging showed a significant response, with decreased disease burden.
CONCLUSIONS: Our case shows a unique presentation of CAD, initially presumed to be myelosuppression secondary to chemotherapy. Instead, a peripheral smear revealed Pembrolizumab to be the cause of cold agglutinin disease. Due to the relatively unknown association between these 2 entities, patient care was delayed. Finally, after initiation of Rituximab therapy, the patient’s CBC began to recover.

Keywords: Anemia, Hemolytic, Autoimmune, Immunotherapy, Lung Neoplasms