title: Antitumor activity of nivolumab on hemodialysis after renal allograft rejection.
abstract: Nivolumab (Opdivo™) is a novel IgG4 subclass programmed death-1 (PD-1) inhibiting antibody that has demonstrated breakthrough-designation anti-tumor activity. To date, clinical trials of nivolumab and other checkpoint inhibitors have generally excluded patients with solid organ transplantation and patients with concurrent immunosuppression. However, organ transplant recipients are at high-risk of development of malignancy as a result of suppressed immune surveillance of cancer.
  
  
  
  We illustrate the outcomes of a 63 year-old type I diabetic female patient who developed pulmonary metastatic,BRAFwild-type cutaneous melanoma 10 years after renal transplantation. After downward titration of the patient's immunosuppressive medications and extensive multidisciplinary review, she was treated with nivolumab in the first-line setting. Within 1 week of administration, the patient experienced acute renal allograft rejection, renal failure and concurrent diabetic ketoacidosis due to steroid therapy. Allograft function did not return, but patient made a full clinical recovery after being placed on hemodialysis. Subsequently, the patient had clinical disease progression off therapy and required re-challenge with nivolumab on hemodialysis, resulting in ongoing clinical and radiographic response.
  
  
  
  This case illustrates multiple practical challenges and dangers of administering anti-PD1 immune checkpoint inhibitors to patients with solid-organ transplantation including need for titration of immunosuppressive medications, risks of allograft rejection, and treatment during hemodialysis.
authors: Department of Medicine, The Ottawa Hospital, 501 Smyth Road, Ottawa, ON K1H 8L6 Canada ; The Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6 Canada.
authors: Michael
authors: M
authors: Ong
authors: The Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6 Canada.
authors: Andrea Marie
authors: AM
authors: Ibrahim
authors: Department of Medicine, The Ottawa Hospital, 501 Smyth Road, Ottawa, ON K1H 8L6 Canada.
authors: Samuel
authors: S
authors: Bourassa-Blanchette
authors: Department of Medicine, The Ottawa Hospital, 501 Smyth Road, Ottawa, ON K1H 8L6 Canada.
authors: Christina
authors: C
authors: Canil
authors: Department of Medicine, The Ottawa Hospital, 501 Smyth Road, Ottawa, ON K1H 8L6 Canada.
authors: Todd
authors: T
authors: Fairhead
authors: Department of Medicine, The Ottawa Hospital, 501 Smyth Road, Ottawa, ON K1H 8L6 Canada.
authors: Greg
authors: G
authors: Knoll
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D000074322:Antineoplastic Agents, Immunological / Q000494:pharmacology / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000628:therapy; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000009:adverse effects; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000556:secondary; D008545:Melanoma / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009367:Neoplasm Staging; D000077594:Nivolumab; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D006435:Renal Dialysis; D012878:Skin Neoplasms / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D014057:Tomography, X-Ray Computed; D000096142:Cutaneous Malignant Melanoma
chemical_list: D000911:Antibodies, Monoclonal; D000074322:Antineoplastic Agents, Immunological; D007166:Immunosuppressive Agents; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab
keywords: Acute allograft rejection; Anti-PD-1 therapy; Hemodialysis; Melanoma; Nivolumab; Organ transplant