Monitoring antibody binding to T cells in a pembrolizumab‐treated patient with lung adenocarcinoma on hemodialysis

Abstract

Recent clinical trials have demonstrated that anti‐PD‐1 blocking antibodies showed remarkable clinical efficacy in a subset of non‐small cell lung cancer (NSCLC) patients. Clinical trials usually exclude patients with renal dysfunction who are receiving hemodialysis (HD). Therefore, it is unclear whether these patients can be safely and effectively treated with pembrolizumab. Here, we present a non‐small cell lung cancer patient on HD who achieved complete remission after one dose of pembrolizumab without severe adverse events. We assessed pembrolizumab binding to peripheral blood T cells in this patient using a method that we recently developed. This is the first report to visualize pembrolizumab binding to T cells in a patient on HD during and after pembrolizumab treatment. The pharmacokinetics of pembrolizumab in this case were similar to those in patients with normal renal function, suggesting that severe renal dysfunction has little influence on the metabolism of pembrolizumab, and is not a contraindication for anti‐PD‐1 treatment. Immune checkpoint inhibitors, including pembrolizumab, may be a vital therapeutic option for lung cancer patients on HD.

Reassessment of the Efficacy of Carboplatin for Metastatic Urothelial Carcinoma in the Era of Immunotherapy: A Systematic Review and Meta-analysis

“…Furthermore, it has been suggested that both cisplatin and carboplatin have a role in promoting antitumor immune responses by reducing the number of myeloid-derived suppressor cells [41,42]. Of particular note, it is also suggested that cisplatin not only enhances T-cell activity, but also induces tumor cell PD-L1 upregulation, thus possibly accounting in part for the additive antitumor activity between cisplatin-based chemotherapy and PD-L1/ programmed death protein-1 (PD-1) inhibition [37,[43][44][45]. Indeed, the expression of PD-L1 in NSCLC cells is shown to be upregulated following preoperative cisplatin-based chemotherapy in NSCLC patients (before vs after chemotherapy, 11% vs 26%; p = 0.017) [36].…”

Chemotherapy plus atezolizumab for a patient with small cell lung cancer undergoing haemodialysis: a case report and review of literature

“…Therefore, we administered carboplatin (AUC = 5, 125 mg/body on day 1), etoposide (40 mg/m 2 on days 1, 2, and 3), and atezolizumab (1200 mg on day 1). The results of previous reports on PD-1/PD-L1 inhibitor for LC patients on HD are summarized in Table 1 [11][12][13][14]. It is not clear how dialysis affects the blood levels of each drug as the blood concentration was not measured.…”

Paclitaxel and carboplatin chemotherapy after platinum‑based chemotherapy and pembrolizumab for metastatic urothelial carcinoma

“…These results suggest that synergy exists between immune checkpoint inhibitors and chemotherapy. In a previous study, the duration of pembrolizumab, a PD-1-blocking antibody, in T cells of non-small-cell lung cancer patients was systematically assessed, and complete binding to T cells was reportedly lost after approximately 20 to 25 weeks ( 24 ). Anti-PD1 also may provide a delayed synergistic effect on subsequent cytotoxic therapy and may contribute to improved therapeutic efficacy through the overlap of circulating anti-PD1 and cytotoxic agents.…”