Immune checkpoint inhibitor use in patients with end-stage kidney disease: an analysis of reported cases and literature review

Abstract

Immune checkpoint inhibitors (ICI), immunomodulatory antibodies that are used to enhance the immune system, have substantially improved the prognosis of patients with advanced malignancy. As use of ICI therapy becomes increasingly widespread across different types of cancer, their use in patients receiving dialysis is likely to increase. In this review, we summarize the current literature on use of ICI in ESKD patients and provide aggregate data from reported cases and series. Based on available pharmacological information, ICIs require no dosing adjustment in ESKD patients. Analysis of the reported cases in the literature demonstrates similar incidence of immune-related adverse events in patients with ESKD receiving dialysis as compared to the general population (49%). Severe reactions graded as 3 and 4 have been seen in fifteen patients (16%). As such, it is important that these patients are monitored very closely for irAE, however the risk of these adverse events should not preclude patients on dialysis from receiving these therapies. Cancer remission (complete and partial) was seen in close to 30% of patients. Stable disease was seen in 28% and progression of disease in approximately 36% of patients. One-third of the patients died. Urothelial and renal cell cancer represented approximately half of all treated cancers, and accounted for approximately 50% of all deaths reported. Additional data in the dialysis population with use of ICI, and involvement in prospective studies, is needed to better assess outcomes, particularly within specific cancer types.

Case Report: Safety and Efficacy of Enfortumab Vedotin in a Patient With Metastatic Urothelial Carcinoma Undergoing Peritoneal Dialysis

“…Similar to chemotherapy, the guidance for monoclonal antibody administration in PD is limited to case reports and single patient pharmacokinetic studies. Monoclonal antibodies have a small volume of distribution following administration, and distribution in the interstitial space is determined by diffusion and antibody binding followed by intracellular degradation ( 13 ). Monoclonal antibodies are too large to be effectively eliminated by dialysis filters, thus the main route of elimination is intracellular catabolism or receptor-mediated endocytosis ( 13 ).…”

“…Monoclonal antibodies have a small volume of distribution following administration, and distribution in the interstitial space is determined by diffusion and antibody binding followed by intracellular degradation ( 13 ). Monoclonal antibodies are too large to be effectively eliminated by dialysis filters, thus the main route of elimination is intracellular catabolism or receptor-mediated endocytosis ( 13 ). There have been several case reports published on the use of anti-PD-1 inhibitor therapies, pembrolizumab and nivolumab, in dialysis patients ( 13 – 15 ).…”

“…Monoclonal antibodies are too large to be effectively eliminated by dialysis filters, thus the main route of elimination is intracellular catabolism or receptor-mediated endocytosis ( 13 ). There have been several case reports published on the use of anti-PD-1 inhibitor therapies, pembrolizumab and nivolumab, in dialysis patients ( 13 – 15 ). However, PD patients comprise only about 3% of the study population examined.…”

Immunotherapy and the Spectrum of Kidney Disease: Should We Individualize the Treatment?

“…Additionally, these patients are normally excluded from most clinical trials with cancer therapies, since most of them are aimed to study the pharmacodynamic and pharmacokinetic characteristics of these drugs. In the case of ICIs, these are not modified by the use of dialysis due to their molecular size ( 36 ) and do not require dose adjustment. Thus, theoretically, the use of ICI in dialysis patients seems to be safe, although the literature on this topic is scarce ( 37 ).…”

“…Cancer that is most associated with the use of ICI in patients undergoing dialysis is renal carcinoma, followed by genitourinary and melanoma. Nivolumab and pembrolizumab are the two most commonly used drugs ( 36 ). Since this population is excluded from clinical trials, evaluating safety in patients undergoing dialysis is a challenge ( 38 ).…”