Abstract 2249: Checkpoint inhibitor therapy after dendritic cell vaccination elicits tumor response in mesothelioma patients

Abstract

Abstract In mesothelioma most patients do not have functional T cells present in the tumor. Therefore, PD-1/PD-L1 checkpoint inhibitor (CI) therapy is likely to induce an anti-tumor response in only a small portion of patients. Activated autologous dendritic cells (DCs) that have been directed against mesothelioma tumor cells have been shown to reinvigorate T cell responses. This T cell response that is induced is prone to be blocked by the tumor using the PD-1/PD-L1 mechanism. Earlier, we published the results of three phase I/II trials in which patients were treated with DC immunotherapy as first line therapy of after completion of first line chemotherapy. 9 patients were subsequently treated with checkpoint inhibitor therapy in several trials and compassionate use programs. Six patients were treated with nivolumab, two with pembrolizumab and one patient was treated with combination treatment of nivolumab and ipilimumab. In all patients, the initial biopsy was stained for PD-L1 and TIM3, in five patients, repeat biopsy was done at time of progression. Radiological response was measured on CT scan using modified response evaluation criteria in solid tumors (RECIST). A radiological partial response was seen in three patients after PD-1 inhibition, stable disease was seen in five patients and one patients had progression of disease as best response on CI therapy, giving a disease control rate of 88%. No CTCAE grade 3-4 adverse events were seen. Updated adverse events, median PFS and OS will be presented at the meeting, as well as correlation of response with PD-L1 and TIM3 status. We conclude that CI treatment after DC immunotherapy is safe and feasible. In addition, after induction of a T cell response, disease control could be achieved in all but one treated patient on subsequent CI therapy. This report is a proof of concept that the induced T cell response from DC immune therapy may be blocked by PD-L1 upregulation from the tumor which in turn can be targeted by CI. Citation Format: Robin Cornelissen, Robert Belderbos, Joachim Aerts. Checkpoint inhibitor therapy after dendritic cell vaccination elicits tumor response in mesothelioma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2249.