Sirolimus associated with less malignancy but an increased mortality after kidney transplantation
A group from Ottawa, led by Greg Knoll, have published an important systematic review of risk of cancer in patients who had sirolimus included with their immunosuppression de novo as well as those who were converted at some stage after transplantation to sirolimus. The study also included a meta-analysis of individual patient data. This was available from 5,676 patients from 21 randomised trials. Sirolimus was associated with a 40% reduction in the risk of malignancy and particularly in the reduction of the risk of a non-melanoma skin cancer, compared with patients who did not receive sirolimus. The most marked effect was seen in patients who were converted to sirolimus at some time following the transplant procedure.
However sirolimus was associated with a 43% increased risk of death compared with controls. The causes of death in sirolimus patients were either infection or cardiovascular. The authors suggest that although there is a reduction in the risk of malignancy, the increased risk of death in patients receiving sirolimus does not justify its use. This may well be true but this is a critically important study and no doubt will trigger others to look specifically at mortality in their patients who are receiving, or have received, an mTOR inhibitor.
One thought on “Sirolimus associated with less malignancy but an increased mortality after kidney transplantation”
Leave a Reply
You must be logged in to post a comment.
This is a clearly presented article, and they have individual patient data from 21 trials in here which is quite a feat.
There are some caveats: the study was funded by Pfizer, and data from 7 of the trials came from Pfizer. I suspect that these trials were probably some of the largest, meaning that the bulk of the data was in these trials (although it is not easy to tell from the manuscript). However, I like the fact that they have gone on to compare the patient-level data with aggregate data in the trials for which they were not able to get it – the fact that these analyses give similar results strengthens the conclusions.
What I am not sure about is how one assesses the presence of heterogeneity in individual patient-level data. The multivariate analysis used will correct for things that they have tested for, but there is the possibility of other parameters that differ between trials affecting the outcomes measured. There is also likely to be a form of “publication” or “reporting” bias for the trials that made individual patient data available.
I am not sure that this would change practice in the majority of units, especially given that the effect on mortality seen appears to be smaller/absent when lower sirolimus target levels are used (as is the case in the majority of late conversion protocols).