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Summary of topic by Mona Doshi, MD
The goal of any
course of cancer treatment is to prevent and/or kill future growth of
malignant cells. Sometimes this can be challenging as some cancer cells
gain the ability to “trick” the immune system into thinking the cancer
cells are normal healthy cells. Doctors are seeing promise in a group of
drugs called immune checkpoint inhibitors, which actually “open up the
immune system” and allow the immune system(T-cells) to recognize and
attack the cancer. Two recent reviews published in early 2017 have
summarized the effects of immune check point inhibitors (ICI) on the
kidney.
We shall be discussing NEJM letter published on Jan 12th 2017. While
effective in most cancer patients, this course of treatment has been
less successful in kidney transplant patients because activating the
immune system causes the patient’s body to start rejecting their donor
kidney. Five prior cases published in the literature of renal
transplant patients getting PD-1 inhibitors have resulted in rejection. The rejections were mostly seen in PD-1 inhibitor based therapy compared to CTLA-4 therapy.
In addition, the 2 cases of liver transplant where these agents were
used and 1 case of heart transplant didn’t lead to a rejection episode.
But in the renal transplant patients, 5 cases have now been reported of
leading to acute cellular and antibody mediated rejection when PD-1
inhibitor was administered. In a recent case correspondence in NEJM Jan 12th 2017 issue,
the authors observed during the treatment of a patient living with
cancer who had a kidney transplant that the combination of steroids and
sirolimus (an immunosuppressant that has anti cancer properties), could
prevent a patient’s body from rejecting the organ during cancer
treatment with ICI.
In the case the
authors observed the treatment of a 70 year-old Caucasian male who
received a kidney transplant in 2010 and recently underwent treatment
for small bowel cancer which had spread to the liver. The patient was
given prednisone, a steroid, and sirolimus prior to incorporating an
immune checkpoint inhibitor (nivolumab). The steroids were started 1
week prior to the starting of nivolumab and continued at a tapered
regimen as mentioned in the manuscript to prevent the immune mediated
reaction seen in prior cases. Steroids didn’t hinder the shrinkage of
the cancer. There was significant response in tumor burden (as shown in
the appendix) and the serum creatinine remained stable (as shown in
appendix). There were no clinical or immunological signs of rejection.
In this forum discussion, as nephrologists, we can try to come up with ways to answer few questions for the oncologists.
1. What is the best treatment strategy for ICI induced AIN (dose, duration of steroids)?
2. What is the best preventive strategy for patients who have had ICI induced AIN and need to continue the targeted therapy?
3.
Given the above single case report, can the above mTOR inhibitor+
steroid strategy be employed in all transplant patients receiving PD-1
inhibitors?
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Sincerely,
The Onco-Nephrology Leadership Team
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