Abstract
The only registered systemic treatment for malignant pleural mesothelioma (MPM) is platinum based chemotherapy combined with pemetrexed, with or without bevacizumab. Immunotherapy did seem active in small phase II trials. In this review, we will highlight the most important immunotherapy-based research performed and put a focus on the future of MPM. PD-(L)1 inhibitors show response rates between 10 and 29% in phase II trials, with a wide range in progression free (PFS) and overall survival (OS). However, single agent pembrolizumab was not superior to chemotherapy (gemcitabine or vinorelbine) in the recent published PROMISE-Meso trial in pre-treated patients. In small studies with CTLA-4 inhibitors there is evidence for response in some patients, but it fails to show a better PFS and OS compared to best supportive care in a randomized study. A combination of PD-(L)1 inhibitor with CTLA-4 inhibitor seem to have a similar response as PD-(L)1 monotherapy. The first results of combining durvalumab (PD-L1 blocking) with cisplatin-pemetrexed in the first line are promising. Another immune treatment is Dendritic Cell (DC) immunotherapy, which is recently tested in mesothelioma, shows remarkable anti-tumor activity in three clinical studies. The value of single agent checkpoint inhibitors is limited in MPM. There is an urgent need for biomarkers to select the optimal candidates for immunotherapy among MPM patients in terms of efficacy and tolerance. Results of combination checkpoint inhibitors with chemotherapy are awaiting.
Highlights
Malignant pleural mesothelioma (MPM) is a rare, aggressive malignancy with limited treatment options
The only registered systemic treatment is platinum-based chemotherapy combined with pemetrexed, with or without bevacizumab
These Dendritic Cell (DC) were tested in 9 MPM patients including 5 subjects pretreated by chemotherapy
Summary
Malignant pleural mesothelioma (MPM) is a rare, aggressive malignancy with limited treatment options. The study with avelumab, a PD-L1 blocker, showed less efficacy with a response rate of 9.4% in 53 patients and a mPFS of 3.9 months [6]. The phase II trials MESOT-TREM-2008 [10] and MESOT-TREM2012 [11] trial showed some promising results and a large randomized controlled trial (DETERMINE) was initiated [12] In both MESOT-TREM trials 29 patients with MPM were included and treated with tremelimumab. Based on the results of the MESO-TREM studies, a large randomized controlled trial (DETERMINE) with higher dosage of tremelimumab was performed. The non-comparative MAPS-II trial, randomizing patients between nivolumab alone or nivolumab with ipilimumab showed clinical activity in both arms with a DCR of 40 and 52%, an ORR of 19 vs 28% and mPFS of 4.0 and 5.6 months respectively. The TGK definition of HPD did impact OS after pooling data from
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