Long-Term Follow-Up of Mesothelioma Patients Treated with Dendritic Cell Therapy in Three Phase I/II Trials

Abstract

Background: Malignant pleural mesothelioma (MPM) is a fatal neoplasm with, if untreated, poor survival of approximately nine months from diagnosis. Until recently, phase II–III immunotherapy trials did not show any significant benefit. The lack of immunotherapy efficacy can be explained by the fact that mesothelioma is a tumor with an “immune desert” phenotype, meaning a non-inflamed tumor characterized by low T-cell infiltration. By administration of DCs, which were ex-vivo cultured, exposed to (tumor-associated) antigens, and subsequently activated, this “immune desert” phenotype might be turned into an “inflamed” phenotype. Three phase I/II studies have been performed and published using activated DCs, which support this concept. We here report on the long-term survival of patients treated with DCs in three phase I/II studies. Methods: Survival data of the phase I/II trials using DC therapy in MPM patients were obtained and subsequently analyzed. In the first two trials, DCs were loaded with autologous tumor lysate. In the third trial, DCs were loaded with allogeneic mesothelioma tumor cell line lysate. Results: In the three studies combined, 29 patients with MPM were treated with DC vaccination between 2006 and 2015. At data cut-off, the median OS was 27 months (95% CI: 21–47 months). OS at 2 years was 55.2% (95% CI: 39.7–76.6%), and OS at 5 years was 20.7% (95% CI: 10.1–42.2%). Conclusions: The long-term survival of DC therapy in MPM in these three trials is promising, which is the basis for the randomized phase II/III DENIM study. This DENIM study is currently enrolling, and the results of which have to be awaited for definite conclusions.

Keywords

• malignant pleural mesothelioma
• dendritic cells
• vaccination
• tumor lysate
• immunotherapy