Specific immunosuppressants and immunotherapy are not enough to prevent organ rejection in patients undergoing skin cancer treatment who have also received a kidney transplant, according to a clinical trial published in the Journal of Clinical Oncology.
People who have received an organ transplant are two to four times more likely to get cancer, according to the National Institutes of Health, and are particularly at heightened risk for skin cancer.
Because traditional chemotherapy and immunotherapy treatments can result in rejection of a transplanted organ, transplant recipients with skin cancer are often excluded from drug trials and have limited treatment options, said Sunandana Chandra, MD, MS, associate professor of Medicine in the Division of Hematology and Oncology and a co-author of the study.
“At this time, we can only study the effects of immunotherapies in skin cancer patients who have a kidney transplant, if they are willing to accept the potential risk of transplant rejection and subsequent initiation of dialysis,” said Chandra, who is also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “Even though there’s a high unmet need of effective systemic skin cancer therapy in patients with kidney transplants, we generally have not been able to study these patients prospectively in an organized, well-designed trial as they were historically not eligible for clinical trials.”
In the study, investigators administered the immunosuppressant tacrolimus and anti-inflammatory drug prednisone alongside cancer immunotherapy drugs nivolumab and ipilimumab to kidney transplant recipients who also had skin cancer. Patients received tacrolimus and prednisone once daily and then were given immunotherapy with nivolumab, according to the study.
After 16 weeks of treatment, investigators found that tacrolimus and prednisone were not enough to prevent organ loss in kidney transplant recipients with skin cancer. Among the eight patients in the study, all experienced continued tumor growth despite the immunotherapy, and one patient experienced treatment-related donor organ loss.
“I think the lessons we have learned here are that we need to re-evaluate the type of immunosuppressant we’re treating these patients with and perhaps the type of immunosuppressant drug and/or doses used in this trial were insufficient. We also need to think about how we want to give the immunotherapy drugs,” Chandra said.
Moving forward, the information investigators have learned will be incorporated into an updated trial for kidney transplant patients with skin cancer, she said.
“We hope to not only see if we can figure out ways to increase efficacy, meaning increased effectiveness of these drugs on these cancers, but we also would like to decrease the risk to the donor organ,” Chandra said. “The lack of trials for these patients is striking and something we’re trying to change.”
The study was supported in part by National Cancer Institute grant UM1 CA186691, the Bloomberg-Kimmel Institute for Cancer Immunotherapy, the Marilyn and Michael Glosserman Fund for Basal Cell Carcinoma and Melanoma Research, the Mary Jo & Brian C. Rogers Fund, Moving for Melanoma of Delaware, Barney Family Foundation, Laverna Hahn Charitable Trust, Bristol-Myers Squibb, and The Raymond and Melody Ranelli Fund.
