EFFICACY AND SAFETY OF IMMUNE CHECKPOINT INHIBITORS IN HEMODIALYSIS PATIENTS WITH MALIGNANCIES.

Immune checkpoint inhibitors (ICIs) are novel anticancer agents that modulate the immune system to enhance antitumor immunity. Clinical trials have provided promising efficacy of ICIs to improve the prognosis of patients with advanced malignancies. Pharmacologically, these agents are not primarily excreted via the kidneys; therefore, their use should also be theoretically feasible in patients undergoing maintenance hemodialysis. However, individuals with end-stage renal disease were excluded from clinical trials, limiting understanding of ICIs safety and efficacy in this patient cohort.

We conducted a retrospective analysis of patients undergoing maintenance hemodialysis who were treated with ICIs at Kyoto University Hospital and Otowa Memorial Hospital between January 2016 and December 2024. We examined patient characteristics, primary cancer type, treatment regimens, tumor response, progression-free survival and overall survival, and incidence of immune-related adverse events (irAEs).

A total of 13 patients met the inclusion criteria. The mean patient age was 69 years, all were male, and median period from dialysis initiation was 53 months. 7 (54%) patients were treated with ICIs for renal cell carcinoma (RCC), while 6 (46%) patients had non-RCC malignancies (gastric carcinoma (n=3), urothelial carcinoma (n=1), malignant pleural mesothelioma (n=1), glottic carcinoma (n=1)). Five patients received dual ICI therapy (nivolumab combined with ipilimumab or similar regimens), 2 patients received combination therapy of ICI with lenvatinib, and 6 patients were treated with single ICI. All the patients received ICIs on non-dialysis days at the same dose as in non-dialysis patients. Among patients with RCC, partial response (PR) was achieved in 5/7 (71%) cases, and stable disease (SD) was achieved in 2 cases. Notably, in 2 RCC cases that were initially considered unresectable at the time of diagnosis, treatment with ICIs brought about significant tumor shrinkage, enabling subsequent curative resection. Median progression-free survival and overall survival in patients with RCC were 233 and 558 days, respectively. In patients with non-RCC malignancies, SD was achieved in 4 (67%) cases, while progressive disease (PD) was observed in 2 cases. Median progression-free survival and overall survival in patients with non-RCC malignancies were 156 and 352 days, respectively. irAEs occurred in 7/13 (54%) patients in total, and of these, Grade ≥3 irAEs were observed in 4 cases (dermatitis, hypophysitis, pneumonia, and enteritis, n=1 each). None of the patients who developed irAEs were able to resume ICI therapy. In RCC cases, irAEs were observed in 5/7 cases, and 4 cases required treatment with corticosteroids. In non-RCC cases, irAEs were observed in 2/6 cases, and 1 case required corticosteroid treatment. No significant correlation was observed between tumor response and the incidence of irAEs.

Patients with RCC on maintenance hemodialysis demonstrated significantly better tumor response rate of 71% in this study compared with those previously reported rate of 41% in non-dialysis patients, while the organs affected by and the incidence of irAEs were equivalent to their counterparts. ICIs should be considered an effective therapeutic option for patients with malignancies undergoing maintenance hemodialysis.