Nivolumab (Opdivo▼), pembrolizumab (Keytruda▼): reports of organ transplant rejection

There have been reports of rejection of solid organ transplants in patients treated with nivolumab or pembrolizumab. Ipilimumab (Yervoy▼) may also interfere with immunosuppressive therapy, increasing the risk of graft rejection.

Advice for healthcare professionals:

  • rejection of solid organ transplants, including renal and corneal grafts, has been reported in the post-marketing setting in patients treated with programmed death receptor 1 (PD-1) inhibitors
  • consider the benefit of treatment with nivolumab or pembrolizumab versus the risk of possible organ transplant rejection for each patient
  • some cases of rejection occurred in association with ipilimumab, which carries a warning that it may interfere with immunosuppressive therapy, resulting in an increased risk of graft rejection


Nivolumab (Opdivo▼) and pembrolizumab (Keytruda▼) are immune checkpoint inhibitors that specifically block the activity of a protein called programmed death receptor 1 (PD-1).

These drugs are indicated for the treatment of various cancer types, including malignant melanoma, non-small-cell lung cancer, and relapsed or refractory classical Hodgkin’s lymphoma. For more information on the authorised indications, see the summaries of product characteristics for nivolumab and pembrolizumab.

Data summary

A European review of worldwide data concluded that nivolumab and pembrolizumab may increase the risk of rejection in organ transplant recipients.

The review assessed all cases received up to November 2016 and identified 9 patients who had transplant rejection after receiving nivolumab and pembrolizumab.

Of the 5 patients receiving nivolumab, 3 had kidney transplant rejection, 1 had corneal transplant rejection, and 1 had skin graft rejection.

Four patients receiving pembrolizumab had kidney transplant rejection; 2 patients were diagnosed after biopsy.


Ipilimumab (Yervoy▼), another immune checkpoint inhibitor, specifically blocks the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and is indicated for malignant melanoma.

In 2 of the 9 reports of rejection, patients started treatment with ipilimumab before receiving nivolumab or pembrolizumab. Ipilimumab is known to increase the risk of graft rejection.

Call for reporting

Please continue to report any suspected adverse reactions to nivolumab, pembrolizumab, and ipilimumab on a Yellow Card.

Article citation: Drug Safety Update volume 10 issue 12, July 2017: 3.

Published 20 July 2017