Abstract Introduction: Pembrolizumab has improved outcomes in triple negative breast cancer (TNBC), but its use can be associated with serious immune-related adverse events. Autoimmune hemolytic anemia (AIHA) has been reported in patients treated with immune-checkpoint inhibitors for other malignancies, but to our knowledge, it has not been previously described in patients with breast cancer (BC). Herein, we report a case of pembrolizumab-associated AIHA during neoadjuvant therapy for locally advanced TNBC. Case Presentation: A 72-year-old postmenopausal woman with a cT3N3 TNBC started treatment with chemotherapy in combination with pembrolizumab per the KEYNOTE-522 protocol. She completed four cycles of paclitaxel, carboplatin, and pembrolizumab with a good clinical response. The second cycle of doxorubicin and cyclophosphamide (AC) plus pembrolizumab was delayed due to neutropenic fever and symptomatic anemia (hemoglobin 7.1 g/dL). She received one unit of packed red blood cells. At that time, the indirect bilirubin was normal, and her hemoglobin rose appropriately to 11g/dL. However, two weeks later she developed worsening macrocytic anemia (hemoglobin 9.8 g/dL) and evidence of hemolysis: indirect bilirubin elevation (2.3 mg/dL), low haptoglobin ( 10 mg/dL), reticulocytosis (5.8%), and LDH elevation (840 U/L). The patient had no prior history of a blood transfusion, making a delayed hemolytic transfusion reaction less likely. A direct antiglobulin test (DAT) was drawn after steroid initiation and was negative. Due to these findings, she started prednisone 1mg/kg. Pembrolizumab was discontinued and prednisone was tapered over four weeks. Hemolysis resolved (Hemoglobin stabilized at 11g/dL, LDH, indirect bilirubin, and haptoglobin normalized). She completed the remaining 3 cycles of AC uneventfully. Although her hemoglobin declined again during subsequent AC chemotherapy it remained stable, consistent with expected chemotherapy-induced anemia. Importantly hemolysis markers remained normal during this period, supporting resolution of the autoimmune process. Discussion: AIHA is an uncommon but potentially life-threatening immune related adverse event associated with checkpoint inhibitors such as pembrolizumab. In this patient, laboratory diagnostic clues included anemia with reticulocytosis, elevated LDH/indirect bilirubin, and low haptoglobin. While the DAT was negative, it was done after corticosteroid treatment started. The temporal association with pembrolizumab exposure and clinical resolution following its withdrawal and steroid therapy supports a diagnosis of pembrolizumab-induced AIHA. Clinicians should maintain a high index of suspicion since prompt recognition and treatment with corticosteroids is critical. Citation Format: A. R. Slaybe, A. C. Sandoval Leon. Autoimmune Hemolytic Anemia Triggered by Neoadjuvant Pembrolizumab in Triple Negative Breast Cancer: A Case Report abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-06-20.
Slaybe et al. (Tue,) studied this question.