Immune check point inhibitors and renal transplant: the saga continues with more twists and turns

Immune check point inhibitors have been used sparingly in the organ transplant world.
A review last time we did on this topic in Journal of Onconephrology listed a list of cases that led to rejection in majority of the cases when PD-1 inhibitors( nivolumab or pembrolizumab) was used alone or in combination with CTLA-4 inhibitors. 

Last year, a case from our institution(Barnett et al.) showed that if pre emptive steroids and mTOR inhibitors were used, rejection could be potentially prevented in a single case report. To date, to my knowledge, this has not been repeated. Nevertheless, new cases have come to light showing more rejection but a few showing no rejection despite PD-1 inhibitor use.

The table below is an updated list since our last publication in JON and NEJM(appendix)

Transplant type	ICI therapy	Time	Rejection(yes/no)	Graft loss(yes/no	Reference
DDRT	Ipilimumab	None	No	No	Lipson et al
DDRT	Ipilimumab	None	No	No	Lipson et al
DDRT	Ipilimumab +pembrolizumab	5 weeks	Cellular and antibody rejection	Yes	Alhamad et al
DDRT	Pembrolizumab	8 weeks	Cellular rejection	Yes	Lipson et al
DDRT	Ipilimumab +  nivolumab	5 weeks	Cellular rejection	Yes	Spain et al
DDRT	Nivolumab	6 weeks	Cellular rejection	Yes	Bolis et al
DDRT	Pembrolizumab	6 weeks	Cellular rejection	Yes	Kwatra et al
DDRT	Nivolumab	3 weeks	Cellular rejection	Yes	Deltombe et al
DDRT	Ipilimumab + nivolumab	1 week	Cellular rejection	Yes	Miller et al
LRRT	Pembrolizumab	None	No	No	Saadat et al
DDRT	Pembrolizumab + chemo	None	No	No	Wu et al

The last four cases shed some new light. Miller et al and Deltombe et al showed two cases that had converted to everolimus but still had rejection. No pre treatment of steroids were used. Saadat et al and Wu et al, no immunosuppressive treatments were made and PD-1 inhibitors were used and no rejection happened but cancers did progress. Saadat et al did use high levels of sirolimus during the treatment of the PD-1 inhibitor. The last case is fascinating as no pre- treatment was used and the patient had a DDRT and despite getting cisplatin, bevacizumab and PD-1 inhibitor, the creatinine remained stable. Could VEGF inhibition be protective here? Why did this patient not reject? Perhaps The Barnett et al case and Saadat et al didn’t reject due to being LRRT and having accommodation and tolerance but Wu case is intriguing.

A twitter poll I did on what folks are doing around showed the following when using PD-1 inhibitors in the renal transplant world.

Are you using Pd-1 inhibitors in renal Transplant patients ?

— Kenar Jhaveri (@kdjhaveri) January 1, 2018

What are your thoughts?