title: Risk of posttransplant lymphoproliferative disorder associated with use of belatacept.
abstract: OBJECTIVE
  Published evidence on a rare but serious malignancy associated with use of the first biological agent approved for long-term maintenance immunosuppression in renal transplant recipients is reviewed.
  
  
  CONCLUSIONS
  Belatacept (Nulojix, Bristol-Myers Squibb) is approved by the Food and Drug Administration for use in combination therapy to prevent renal graft rejection in patients who are Epstein-Barr virus seropositive. Belatacept appears to offer some advantages over calcineurin inhibitor-based regimens (e.g., no need for therapeutic drug monitoring), but its use poses a risk of posttransplant lymphoproliferative disorder (PTLD), a rapidly progressing and often lethal malignancy. The efficacy and safety of more-intensive and less-intensive belatacept regimens were established in two Phase III clinical trials, which found that rates of patient and graft survival were comparable to those in cyclosporine users; belatacept was shown to be superior in preserving renal function. The occurrence of PTLD, particularly PTLD involving the central nervous system, in 0-4% of belatacept-treated patients in clinical trials prompted postmarketing initiatives: (1) implementation of a risk evaluation and mitigation strategy (REMS) program to help ensure the safe and proper use of belatacept, (2) longitudinal studies to better define the risks and outcomes of belatacept therapy, and (3) a manufacturer-created patient registry to track belatacept use and encourage voluntary reporting of associated adverse events.
  
  
  CONCLUSIONS
  Appropriate patient selection and adherence to REMS requirements, including patient counseling and facilitation of registry enrollment, are essential in mitigating the increased risk of PTLD associated with belatacept therapy.
authors.affiliation: Spencer T. Martin, Pharm.D., BCPS, is Solid Organ Transplant Clinical Specialist, Department of Pharmacy, Hartford Hospital, Hartford, CT; at the time of writing, he was Cardiac Transplant Clinical Specialist, Department of Pharmacy, NewYork-Presbyterian Hospital, New York, NY. Jaclyn T. Powell, Pharm.D., is Liver Transplant Clinical Specialist, Department of Pharmacy, NewYork-Presbyterian Hospital. Monank Patel, Pharm.D., is Postgraduate Year 2 Oncology Resident, Department of Pharmacy, Mount Sinai Hospital, New York. Demetra Tsapepas, Pharm.D., is Renal Transplant Clinical Specialist, Department of Pharmacy, NewYork-Presbyterian Hospital.
authors.forename: Spencer T
authors.initials: ST
authors.lastname: Martin
authors.forename: Jaclyn T
authors.initials: JT
authors.lastname: Powell
authors.forename: Monank
authors.initials: M
authors.lastname: Patel
authors.forename: Demetra
authors.initials: D
authors.lastname: Tsapepas
mesh_terms: D000069594:Abatacept; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects* / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000379:methods; D008232:Lymphoproliferative Disorders / Q000139:chemically induced* / Q000473:pathology; D010353:Patient Education as Topic / Q000379:methods; D018579:Patient Selection; D012306:Risk; D012308:Risk Management
chemical_list: D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D000069594:Abatacept; D016572:Cyclosporine