Metastatic Urothelial Carcinoma from Transplanted Kidney with Complete Response to an Immune Checkpoint Inhibitor

Abstract

Background. Donor-derived malignancy is a rare complication in patients who undergo organ transplant. Approaches to treatment have largely been individualized based on clinical circumstances given the lack of evidence-based guidelines, with therapeutic options ranging from discontinuation of immunosuppression and transplantectomy to the addition of chemotherapy or radiotherapy. Case Presentation. Herein, we describe a 60-year-old woman with metastatic donor-derived upper tract urothelial carcinoma (UTUC) discovered nine years postrenal transplant. Molecular diagnostic studies using polymerase chain reaction amplification of short tandem repeat alleles and HLA tissue typing proved that the urothelial carcinoma originated from donor tissue. She achieved sustained complete remission with transplant nephroureterectomy, retroperitoneal lymphadenectomy, immunosuppression withdrawal, and immunotherapy with pembrolizumab. Routine radiologic surveillance has demonstrated 15-month progression-free survival to date off pembrolizumab, and she is now under consideration for retransplantation. Conclusions. Immunotherapy using checkpoint inhibitors can serve as a novel treatment option for patients in the clinical predicament of having a solid organ transplant and simultaneous metastatic malignancy. In this report, we also discuss the oncogenic potential of BK virus, the use of checkpoint inhibitors in urothelial carcinoma, and the feasibility of retransplant for this patient population.

An Unusual Presentation of Metastatic BK Virus-Associated Urothelial Carcinoma Arising in the Allograft, Persisting After Transplant Nephrectomy

“…While urothelial carcinoma is the most frequently reported BK virus-associated carcinoma arising in the allograft (7 of 10 reports), renal cell carcinoma has also been reported (3 of 10 reports) . 1,2,[4][5][6][7][8][9][10][11] They include transplants from deceased (7 of 10 reports) and living donors (3 of 10 reports). Although most patients had a known BK nephropathy history (7 of 10 reports), the interval between BK nephropathy and development of a BK virus-associated allograft carcinoma is unpredictable.…”

“… 3 BK virus-associated carcinomas have been reported in patients posttransplant, and many have postulated that BK virus, too, may play a role in oncogenesis. 1 , 2 , 4 ‐ 11 Of note, however, there have also been reports of carcinomas in renal transplant patients that appear to lack BK virus involvement. 3 This has led some to postulate that rather than playing a role in oncogenesis, BK virus is merely an “innocent passenger” infection in tumor cells.…”

Donor-Derived Urothelial Carcinoma in Renal Transplant Recipients

“…However, 79% of all malignancies in this study were skin cancers, and none was from a urothelial origin [ 17 ]. Only two prior reported cases have shown benefits of donor-derived renal allograft UC treated checkpoint inhibitors, one showing 15 months of progression-free survival after graft excision and pembrolizumab monotherapy [ 18 ]. The other case was locally invasive upon presentation and had partial response to combined treatment with pembrolizumab, bevacizumab, cisplatin, and gemcitabine [ 19 ].…”

Chemotherapy, targeted therapy and immunotherapy: Which drugs can be safely used in the solid organ transplant recipients?

“…So far, approximately, 230 SOT recipients treated with CPI has been reported in the literature. Compared with liver and heart transplant recipients, kidney transplant recipients, despite the highest rate of rejection, have the lower mortality rate [ 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ].…”

“… Response refers to tumor shrinking. Numbers in the table are extracted from the systematic review by d'Izarny‐Gargas [ 12 ] updated with published literature beyond 1 November 2019 [ 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ]. …”