Introduction

The prognosis of metastatic upper tract urothelial cancer (mUTUC) refractory to the standard chemotherapy is very short. To address the affordability of personalized peptide vaccination (PPV) for mUTUC patients refractory to the standard chemotherapy from views of safety, immune responses, and clinical benefits.

Methods

A phase II trial of PPV immunotherapy was conducted for patients with mUTUC refractory to the standard chemotherapy. Eligible patients were human leukocyte antigen (HLA) A02, A24, A26, or A03 superfamily positive. A maximum of four HLA-matched peptides was selected based on the preexisting immunoglobulin G (IgG) responses against the 31 warehouse peptides and administered every 1 to 2 week. The overall survival (OS) time was estimated by the Kaplan-Meier method. Association between pre-vaccination biomarkers, including immune responses, and OS were evaluated by univariate and multivariate analyses with the Cox regression model, and by the Kaplan-Meier method with the log-rank test.

Results

Among 48 patients entered, 28 patients received PPV combined with salvage chemotherapy based on physicians&[prime] choice, and 20 patients received PPV alone since of ineligible due to potential intolerance to chemotherapy. Although no PPV-related severe adverse events were noted, 1 or 12 of 28 patients of the former group dropped before 1st or 2nd cycle due to disease progression, whereas dropped 7 or 16 of 20 patients of the latter group (p=0.002). Peptide-specific cytotoxic T lymphocyte (CTL) activity before PPV was scarcely detectable, but boosted in about half of patients tested after PPV. Median survival time (MST) of all 48 patients was 7.3 months (M) with 13.0 M for 28 patients under PPV and salvage chemotherapy and 4.5 M for 20 patients under PPV alone (p=0.08). Unfavorable prognostic factors by multivariate Cox regression analysis were higher numbers of Bellmunt risk factors (p=0.027) and higher levels of pre-vaccination BAFF (p=0.002). Notably, both peptide-specific CTL and IgG boosting were favorable prognostic factors, suggesting a causal relationship between immune responses and clinical efficacy in PPV.

Conclusions

Further clinical trials of PPV would be warranted for mUTUC because of the safety, immune boosting, and potential clinical benefits. Our data might provide promising evidence of clinical benefit of PPV for patients with mUTUC refractory to the standard chemotherapy.

Funding

none