Systematic Review of the Safety of Immune Checkpoint Inhibitors Among Kidney Transplant Patients

Abstract

Introduction: Kidney transplant (Ktx) recipients are excluded from clinical trials of immune checkpoint inhibitors. The aim of this systematic review was to assess the safety of immune checkpoint inhibitors among Ktx patients. Methods: A literature search was conducted using MEDLINE, EMBASE, and Cochrane Database from inception through April 2019. We included studies that reported outcomes of Ktx recipients who received immune checkpoint inhibitors for cancer treatment. Outcomes of interest were allograft rejection and/or allograft failure. Results: Twenty-seven articles with a total of 44 Ktx patients treated with immune checkpoint inhibitor were identified. Of 44 Ktx patients, 18 were reported to have acute rejection. Median time from immune checkpoint inhibitors to acute rejection diagnosis was 24 (interquartile range, 10-60) days. Reported types of acute allograft rejection were cellular rejection (33%), mixed cellular and antibody-mediated rejection (17%), and unspecified type (50%). Fifteen (83%) had allograft failure and 8 (44%) died. Three patients had a partial remission (17%), 1 patient achieved cancer response (6%), and 5 patients had stable disease (28%). Conclusion: The findings of our study raise awareness of the increased risk for acute allograft rejection/ failure following immune checkpoint inhibitors for cancer treatment among Ktx patients, in particular with programmed cell death 1 (PD-1) inhibitors. Future large-scale clinical studies are required to appraise the pathogenesis and plan optimal balanced therapy that helps sustain graft tolerance.

Immune Checkpoint Inhibitors and Immune-Related Adverse Renal Events

“…Three patients had partial cancer remission (17%), 1 patient achieved cancer response (6%), and 5 patients had stable disease (28%). 31 Similar to other studies, the PD-1 pathway appears to be more commonly associated with the graft rejection/failure, suggesting that this pathway may play a more critical role in allograft tolerance.…”

“…Importantly, AKI can develop earlier, especially when CTLA-4 and PD-1 signaling blockade are combined or after several months to more than a year after ICI treatment discontinuation. 18 , 24 , 31 The severity of AKI varies, but most of the cases described were Kidney Disease: Improving Global Outcomes AKI stage 2 and stage 3 at the time of diagnosis. 10 , 32 The clinical and laboratory features of ICI-associated AKI are similar to those observed with AKI caused by other drug-induced AINs with essentially “bland urinalysis,” subnephrotic range proteinuria, and sterile pyuria, unless a vascular and glomerular lesion is present.…”

“…Previous reports on transplant recipients identified patients who experience kidney allograft graft rejection after combination therapy or PD-1 monotherapy. 31 , 61 Ipilimumab monotherapy in patients who received kidney transplantation appeared to have more favorable results than PD-1 pathway blockade. 62 In 1 small series, 6 patients with minimized immunosuppression for cancer were treated with ipilimumab.…”

Clinical outcomes of solid organ transplant recipients with metastatic cancers who are treated with immune checkpoint inhibitors: A single‐center analysis

“…Indeed, previous reports have shown high rejection rates in recipients who are treated with ICIs. 7,8,14 Abdel-Wahab et al reported a 40% risk of early rejections (median, 21 days), which primarily were responsible for allograft failure and subsequent death. 7 In their study, the highest risk of rejection was found among kidney transplant recipients compared with other SOTRs.…”

Balancing Cancer Immunotherapy Efficacy and Toxicity

“…79 Kidney transplant recipients must consider the risk of returning to dialysis, because up to one-third may have allograft failure. 80 The verdict: Can the patient be rechallenged?…”