Background: Dual immune checkpoint blockade (DICB) is utilized for a variety of malignancies. These therapies have a unique and often unpredictable side effect profile compared to conventional chemotherapy. We describe a lethal case of aplastic anemia (AA) as a result of DICB and a review of the literature regarding this rare entity.
Case Presentation : A 64-year-old male underwent complete resection for right renal cell carcinoma. He developed metastasis 1 year after resection and was started on nivolumab 240 mg and ipilimumab 1mg/kg every 21 days. After 4 cycles, he had an asymptomatic elevation of liver function tests (LFT) with a total bilirubin of 6.4 mg/DL (Ref Range 0.2-1.2 mg/dL). Immunotherapy was discontinued, and he started IV methylprednisolone. His LFTs normalized after 5 weeks of steroid taper and CT demonstrated complete response.
6 months after his final dose of DICB, he developed progressive fatigue and a petechial rash. Labs were signi cant for white blood cell count of 0.9 K/cm 2 (absolute neutrophil count of 0.3 k/cm 2), hemoglobin of 12 g/dL and platelets of 11 K/cm 2. His complete blood count 2 weeks prior was normal. A bone marrow biopsy demonstrated severely hypocellular marrow (10%) with marked decrease in all hematopoietic precursors. He was treated for DICB AA and started on 1mg/kg prednisone, granulocyte colony stimulating factor and erythropoietin.
After no count recovery he was started on antithymocyte globulin and received 7 doses. Despite aggressive supportive care and prophylactic antibiotics, he developed bacteremia and died of septic shock four weeks after admission.
Discussion: On review of the literature, there are only two reported cases of DICB AA. Our particular case has a few unique features. First, hepatotoxicity developed prior to AA. Second, pancytopenia occurred 6 months after his last dose of DICB. There are no other case reports of AA so far out from last infusion.
Conclusion: This case demonstrates the need to promptly recognize rare toxicities of immunotherapies such as AA and identify effective therapies for serious toxicities that are not steroid responsive.
