Immunotherapy combinations may aid patients with advanced skin cancers following kidney transplants

The study, published in the Journal of Clinical Oncology, revealed a novel drug combination aimed at boosting the immune system to combat advanced, potentially life-threatening skin cancers without causing permanent harm to patients' transplanted kidneys. The regimen involved two immune-suppressing drugs to safeguard the transplanted kidney, along with either one or two checkpoint inhibitors, which activate the immune system to target cancer cells.

“Organ transplant recipients develop skin cancers at an exponentially higher rate compared with the general population because they receive long-term immunosuppressive drugs to prevent rejection of the transplanted organ. This can stop the immune system from recognizing and attacking cancers as they form” says Evan Lipson, M.D., an associate professor of oncology at the Johns Hopkins University School of Medicine and Kimmel Cancer Center.

In the Experimental Therapeutics Clinical Trials Network trial, eight kidney transplant recipients with advanced skin cancers received low-dose tacrolimus and prednisone, followed by nivolumab. Upon progression, ipilimumab was added to treatment in six patients. Donor-derived cell-free DNA levels were also monitored every two weeks to explore their potential as a predictor of graft rejection.

Researchers observed that the tumour biopsies demonstrated increased immune activity against cancer with nivolumab, and a complete response in two patients after ipilimumab addition. Additionally, donor-derived cell-free DNA levels rose before serum creatinine increased, indicating a potential for predicting kidney damage from trial medications.

“The completed study introduced two checkpoint inhibitors sequentially because we didn’t want to risk overstimulating the patient’s immune system and harm the transplanted organ,” Lipson said. “But some cutaneous tumors grow so quickly we can’t wait to give a second immunotherapy drug months after starting a first.”

“Going forward, this knowledge may help us intervene earlier and better preserve the transplanted organ, a precious resource,” concluded Lipson.

Reference: DC Dapprich, RH Weenig, AL Rohlinger, etal: Outcomes of melanoma in recipients of solid organ transplant J Am Acad Dermatol 59: 405– 417,2008; https://doi.org/10.1200/JCO.2013.49.2314