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.
Highlights
Malignant pleural mesothelioma (MPM) is a fatal neoplasm of the pleural lining with poor survival of approximately nine months from diagnosis without treatment
The phase 3 randomized CheckMate-743 trial showed an improvement in overall survival (OS) of four months in previously untreated malignant pleural mesothelioma with nivolumab (anti-programmed death-1) and ipilimumab (cytotoxic T-lymphocyte associated protein 4) compared to chemotherapy, leading to FDA approval [4]
This improvement was, significant, more modest—over 2 months, and long-term survival is unknown [5]. That both of these are prespecified subgroup analyses. This first positive trial regarding immunotherapy in MPM is in contrast with non-small cell lung cancer (NSCLC), where mono- immunotherapy targeting PD-(L)1 has become the standard of care based on many positive trials from 2015, showing long-term overall survival [6,7,8]
Summary
Malignant pleural mesothelioma (MPM) is a fatal neoplasm of the pleural lining with poor survival of approximately nine months from diagnosis without treatment. This improvement was, significant, more modest—over 2 months, and long-term survival is unknown [5] It should be noted, that both of these are prespecified subgroup analyses. 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
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