Use of immunotherapy in the renal transplant patient is challenging.
Initial case reports
had shown over and over acute rejections. In 2017, we had tried a novel way to
prevent rejection in a single case report published in NEJM( using mini
steroid pulse and mTOR over CNI use). Since then, we have used this approach
successfully in several patients to allow for good tumor response and prevent
rejection. But one case, two cases, three cases cannot tell the whole
story. More data is needed. A
recent meta-analysis done on use of immunotherapy and transplant patients
showed of 44 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%).
Other
studies similar to this have showed similar rejection rates of 40%. No studies
have tested the clinical efficacy of the use of these agents in renal
transplant patients.
In a recent study published in Kidney International, we collected 69 cases from 23 institutions from US,
Canada and Europe. This is the largest study to look at both transplant
outcomes and efficacy of these agents in renal transplants patients.
Acute rejection rate 42% (29 out of 69), median ICI
to rejection=24 days. Rejection is severe: cellular rejection and mixed
cellular and antibody-mediated rejection are both common. Once rejection
happened, 65% lost allograft.
What are the risk factors of rejection?
Being on 3-agents immunosuppression and mTOR inhibitor use were associated with
LOWER risk of rejection. This is an interesting finding. This is to tell
us the obvious- the less the immunosuppression- the risk for rejection
increases but the mTOR finding is interesting( caution- still low Ns).
Take a look at this paper as
well.
We looked at rejection rate and cancer objective
response rate in skin squamous cell carcinoma (cSCC) and melanoma, two most
common cancer types in our cohort. In cSCC, rejection rate 37.5%, ORR 36.4% and
ICI may be associated with longer overall survival. In melanoma:
rejection rate 54.5% (# of immunosuppression agent-dependent), ORR 40%. OS did
not differ but limited by small # of patients and short follow-up.
An important figure that is
hidden in the supplemental content is below: This tell us the majority of the changes done by centers when immunotherapy was initiated, see the % who increased steroids, converted CNI to mTOR inhibitors, dc CNI , dc MMF. etc. Interesting changes which were made are not at all standardized.

Although our study is to our
knowledge the largest multicenter cohort of patients with advanced solid
malignancies with kidney transplant who received ICI to date, there are several
limitations Firstly it is retrospective and small-sample nature of our cohort
limited our ability to adjust for a number of confounders in multivariable
analysis for the risk of graft rejection. Also less than half of acute
rejection were biopsy proven, which limits the accuracy of the diagnosis of
rejection. The comparison of outcomes using these historical cohorts suffers
from the lack of power due to the small number of cases, but provides a
pragmatic approach to address the risk of rejection and objective response
rate. Lastly, immunosuppression modification was the providers’ choice at each institution
and not standardized.
So what now? This tells us that
immunotherapy is a feasible option for kidney
transplant pts but with very high risk of rejection.
mTOR inhibitor plus steroid
mini-pulse may be effective in preventing rejection?
Or should we continue the immunosuppressive
meds “as is” or at least 2 of them and then give the immunotherapy as efficacy was
amazing in cSCC and prevent the rejection as well.
What this study also told us is
that- stopping the immunosuppression when planning to give immunotherapy doesn’t
really help in cancer outcomes or renal transplant outcomes? So should we be
even stopping them??
A collaborative effort led by Naoka
Murakami from around the world.