Renal transplant patients have been excluded from studies involving immune checkpoint inhibitors, notwithstanding the fact that these patients develop many of the tumour types that are known to respond to such therapy, for fear of such approaches inducing organ rejection. At the time of initiation of this safety trial there had been 9 case reports of checkpoint inhibitors in organ transplant patients. 4 patients suffered fulminant transplant organ failure. In all of these cases there was prior major reduction in standard immunosuppressive medications.
Renal transplant and incurable locally advanced or metastatic cancer that has progressed despite first-line standard anti-tumour treatment or defined metastatic solid tumours, will be enrolled onto a Phase 1 trial. Patients will receive Nivolumab as per approved label. Patients are closely monitored for signs of early rejection and for evidence of safety/toxicity and any anti-tumour effect. Standard inclusion/exclusion criteria for oncological trials were used with the addition of the following: serum creatinine <180 umol/l; absence of Human Leukocyte Antigen (HLA) donor specific antibodies; patients willing to accept potential development of renal transplant failure. All patients were counselled by both a transplant physician and oncologist before signing an ethically approved patient information sheet. Patients were allowed to have minimization of immunosuppression but no medication was completely stopped.
Four patients with metastatic cancer (renal cell, melanoma, SCC head and neck, bladder) were treated with 1, 2, 3 and 9 infusions of nivolumab. One patient has a sustained partial response (after 9 infusions) of their tumour but suffered likely interstitial nephritis which resolved with oral steroid. 3 patients died of progressive cancer after 1,2 and 3 cycles but did not suffer any rejection episodes.
Selected renal transplant patients on low dose immunosuppressive regimens, without significant donor specific allo antibodies, can be treated with nivolumab without rejection episodes and some can have sustained anti tumour responses.
Clinical trial identification
Legal entity responsible for the study
Royal Adelaide Hospital.
Bristol Myers Squibb.
All authors have declared no conflicts of interest.