ASN Communities Onconephrology Live Journal Chat

On Monday, February 27 at 9:00 pm EDT the Onco-Nephrology community is hosting a journal chat on immune checkpoint inhibitors and all ASN members are invited!

Here is how you can participate: 

1. Join the Onco-Nephrology Community, if you haven't already
2. Set your community notification settings for the Onco-Nephrology Community only to “Real Time”
3. Read the Topic Summary on line or listed below.
4. Watch your inbox on Monday for the discussion to start and participate in the chat

If you have any questions about setting up your notifications, please contact ASN Communities Associate Zach Cahill. 

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.

NDT: Izzedine et al

AJN: Wanchoo et al

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?

If you have questions about the content of the chat, contact any of the ONC leaders.

Sincerely,

The Onco-Nephrology Leadership Team

Kenar Jhaveri, MD

Susie Hu, MD

Ilya Glerzerman, MD

Mona Doshi, MD