RDW remained elevated. 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 chemo-therapy. 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 patients CBC began to recover. strong class=”kwd-title” MeSH Keywords: Anemia, Hemolytic, Autoimmune; Immunotherapy; Lung Neoplasms Background Cold agglutinin disease (CAD) is the second most common cause of autoimmune hemolytic anemia. However, the average time to diagnose a patient with CAD is 37.4 months [1]. CAD is mostly ABBV-4083 associated with infections, autoimmune disease, and malignancies. While it has been described in patients with various cancers, the association was believed to be incidental rather than secondary to malignancy [1]. The recent introduction of immunotherapy has revolutionized the treatment of cancer. Tumors use PD-L1 receptors as a means of hiding from the bodys own defense mechanisms C the T cells. Pembrolizumab, a humanized monoclonal antibody, allows the T cells to overcome this defense mechanism by binding to the PD-1 receptor, thereby inhibiting the deactivation of T cells and allowing for the destruction of the tumor cells by T cells. Common adverse effects of immunotherapy include fatigue, pruritis, lymphocytopenia, hyperglycemia, and hypothyroidism. CAD alone had not yet been directly associated with Pembrolizumab therapy. We present a unique case of symptomatic hemolytic anemia caused by CAD after undergoing treatment with Pembrolizumab, leading to ABBV-4083 cessation Rabbit Polyclonal to ELF1 of treatment; a follow-up PET scan showed complete remission. Case Report A 59-year-old woman with a history of alcohol and tobacco abuse presented with a left neck mass. A CT scan showed a right upper-lung mass with right hilar, right mediastinal, and left supraclavicular lymphadenopathy. Fine-needle aspiration confirmed the presence of metastatic adenocarcinoma. PET-CT and MRI of the brain showed no other metastases. The tumor was negative for EGFR, ALK, ROS1, BRAF, MET, and ERBB2. KRAS-G12A mutation was present. Microsatellite status was stable, and the tumor mutational burden could not be determined. PD-L1 immunohistochemistry showed a Tumor Proportion Score (TPS) of 90%. The patient was started on a regimen of Pembrolizumab, Pemetrexed, and Carboplatin, and was also started on vitamin B12 and folic acid supplementation, per protocol. Baseline CBC, CMP, and TSH were within normal limits, except for a WBC 16.46103 cells/dL (neutrophils 92.2%, lymphocytes 5.4%, monocytes 1.0%, basophils 0.4%, eosinophils 0.0%), an elevated total bilirubin (3.7 mg/dL) with a direct bilirubin of 0.4 mg/dL, and alkaline phosphatase of 170 IU/L. She tolerated the first cycle of chemotherapy without any reported issues. At the time of her second cycle, 3 weeks later, her hemoglobin (Hgb) had dropped to 8 g/dL, with an MCV of 100.4 and an elevated RDW of 18.8. The WBC remained elevated at 13.2 and platelets remained normal at 401 k. LDH had increased from 187 to 262, while total bilirubin decreased to 1 1.7 mg/dL. She received her second cycle of treatment as planned. Ten days later, the WBC ABBV-4083 decreased to 2.8, platelets decreased to 36 k, Hgb was 7.6, and total bilirubin normalized to 1 ABBV-4083 1.2, while LDH and MCV decreased to 229 and 87.6, respectively. RDW remained elevated. At the time of the third cycle of therapy, WBC and platelets were normal and Hgb was stable. A week later, she developed melena and Hgb dropped to 6.4 mg/dL, WBC to 2.5, and PLT to 136. She was admitted to the hospital and given PRBCs for symptomatic anemia. EGD showed a Mallory Weiss tear, with oozing of blood and chronic active gastritis/peptic ulcer disease. She was continued on a PPI and discharged. At the time of her fourth and last cycle of therapy, total bilirubin, MCV, WBC, and PLT were normal. LDH and RDW were elevated, with a stable.