In an Australian phase I study reported in The Lancet Oncology, Carroll et al found that maintaining baseline immunosuppression in kidney transplant recipients receiving immune checkpoint inhibitor treatment for advanced solid tumors did not appear to increase the risk of irretrievable allograft rejection or compromise immune checkpoint inhibitor efficacy.
As stated by the investigators, “Most kidney transplant recipients with cancer stop or reduce immunosuppressive therapy before starting treatment with an immune checkpoint inhibitor, and approximately 40% of such patients will develop allograft rejection. Isolated immunosuppression reduction might be associated with organ rejection. Whether immunosuppression manipulation, immune checkpoint inhibition, or both induce organ rejection is difficult to ascertain.”
Study Details
The study enrolled 17 evaluable allograft recipients with a variety of incurable locally advanced or metastatic solid tumors at three Australian centers between May 2017 and August 2021; the trial was stopped due to ongoing difficulties with performance of clinical trials during COVID-19 health restrictions. Patients initiated nivolumab at 3 mg/kg every 14 days for five cycles followed by 480 mg every 28 days for up to 2 years with no change to baseline immunosuppressive treatment. The primary endpoint was the proportion of patients with irretrievable allograft rejection and no evidence of tumor response.
Key Findings
Patients received a median of three nivolumab doses (interquartile range [IQR] = 2–10 doses). Median follow-up was 28 months (IQR = 16–34 months).
No patients had irretrievable allograft rejection without evidence of tumor response. Complete response was observed in four patients (24%) and partial response was seen in five (29%). Mean duration of response was 27.7 months (IQR = 10.0–28.4 months). No patient had allograft rejection without allograft loss and no evidence of tumor response. A total of two patients had allograft rejection: one patient had allograft rejection without allograft loss with tumor response, and one patient had allograft loss with tumor response.
No treatment-related deaths or treatment-related serious adverse events were observed. The most common grade 3 or 4 adverse events were decreased lymphocyte count (24%), fever or infection (24%), decreased hemoglobin (18%), and increased creatinine (18%).
The investigators concluded, “Maintaining baseline immunosuppression before treatment with an immune checkpoint inhibitor in kidney transplant recipients might not affect expected efficacy and might reduce the risk of allograft rejection mediated by immune checkpoint inhibitors.”
Robert P. Carroll, FRACP, of the Central Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Bristol Myers Squibb. For full disclosures of the study authors, visit thelancet.com.
