Abstract: TH-PO159
Checkpoint Inhibitors: The Double-Edged Sword in Kidney Transplant Patients
Session Information
- Drug Events Trainee Case Reports
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Trainee Case Report
- 1500 Onco-Nephrology
Authors
- Mamlouk, Omar, University of Texas Health Science Center at Houston, Houston, Texas, United States
- Workeneh, Biruh, MD Anderson Cancer Center, Houston, Texas, United States
- Mandayam, Sreedhar A., UT MD Anderson Cancer Center, Bellaire, Texas, United States
Introduction
Immunotherapy in the form of Checkpoint inhibitors (CPI) has significantly improved outcome and survival in patients with melanoma and its use has extended to multiple malignancies with good outcome. However around 50% allograft rejection is reported in patients with renal transplant who were treated with CPI with median time of 21 days from initiation of therapy
Case Description
40-year-old man with deceased donor kidney transplantation 7 years ago was diagnosed with metastatic melanoma of the right scalp and underwent wide excision followed by Dabrafenib and Trametinib and then switched to Nivolumab and Ipilimumab. His baseline creatinine was1.8 mg /dl. After 2 cycles of immunotherapy, he was noted to have severe acute kidney injury with Creatinine of 8.5 mg/dl. Renal biopsy showed acute T cell mediated rejection Banff grade IIA and suspicioun for acute antibody mediated rejection with positive peritubular capillaries for C4d. patient was treated for acute rejection with IV Methylprednisolone, rituximab, plasmapheresis (3 sessions) and intravenous immunoglobulin. Patient didn’t have renal recovery and a decision was taken to sacrifice the allograft and continue immunotherapy for Melanoma
Discussion
The complex mechanism for acute rejection in renal transplant patient with use of CPI is still under investigation. One suggested mechanism is related to the inhibition of programmed death ligand 1 (PDL1) that involved in increasing graft tolerance by increasing T regulatory (Treg) cells and limiting the function of effectors T cells.
The current recommendation for treatment of malignancy in patients with renal transplant is to reduce the immunosuppression by stopping the anti-metabolites and possibly switching to mTOR inhibitors. However, these guidelines predated the era of immunotherapy for metastatic malignancy and need to be reevaluated.
Currently there are no established guidelines to help guide the prevention and treatment of acute rejection in this population and no clear studies about the safety of anti-rejection therapy on tumor progression.
With the reported high probability of graft loss, the nephrologist and oncologist should have an extensive discussion with the patient prior to starting CPI to guide with treatment decision that will impact patient lifestyle and cancer response