Is immunotherapy a viable option in treating mesothelioma?

Our plain-English summary of Is immunotherapy a viable option in treating mesothelioma?, by D.W. Dumoulin, J.G. Aerts, R. Cornelissen (Future Oncology, 2017).

The study

• Authors: D.W. Dumoulin, J.G. Aerts, R. Cornelissen
• Journal: Future Oncology
• Published: 2017;13(20):1747-1750
• Type of article: Editorial
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

This editorial, by authors at the Erasmus MC Cancer Institute in Rotterdam, the Netherlands, asked whether immunotherapy could be a viable option in mesothelioma. The authors analysed the steps of the immune response needed for effective tumor killing and reviewed published and ongoing trials at each step. They noted that cisplatinum/pemetrexed gave a survival benefit of 3 months in malignant pleural mesothelioma, and that adding bevacizumab gave nearly 3 more months. They described features that may limit immunotherapy in mesothelioma, including lower mutational load than non-small-cell lung cancer and an immune-suppressive tumor microenvironment. In a first dendritic cell vaccination trial in ten patients, nine showed a significant increase in peripheral blood mononuclear cells and four showed increased cytotoxic activity. A Phase III dendritic cell study (DENIM) with a planned enrollment of 230 patients was about to start. In the DETERMINE trial of 571 patients, tremelimumab gave no survival benefit. Keynote 28 (pembrolizumab) showed a disease control rate of 72%, an objective response rate of 20% and median overall survival of 18 months. NivoMes and JAVELIN showed disease control rates of about 50% and response rates of 28% and 9.4%. The authors also discussed CAR T cells, Listeria-based vaccines, macrophage inhibition and low-dose cyclophosphamide. They concluded that treatment should be tuned to the missing steps in the cancer immunity cycle, that combination treatment can be of added value, and that immunotherapy may prove viable for mesothelioma patients.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This article was an editorial, not a new study. It asked whether immunotherapy could become a workable treatment for mesothelioma. The authors went through the steps the immune system needs to recognize and kill a tumor, and described treatments aimed at each step, drawing on other researchers' published and ongoing trials. Among the trials it described, a placebo-controlled trial of tremelimumab in 571 patients with advanced mesothelioma showed no survival benefit, although the authors said they had seen a response in one patient taking part in that trial. A trial of pembrolizumab in patients whose tumors showed PD-L1 of at least 1% reported a disease control rate of 72%, an objective response rate of 20% and a median overall survival of 18 months. Trials of nivolumab and avelumab, which did not select patients by PD-L1, reported overall response rates of 28% and 9.4%. The authors wrote that most mesothelioma tumors have low T-cell infiltration. They concluded that treatment should be matched to the missing steps, that combinations may add value, and that immunotherapy may prove to be a viable option.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Editorial (opinion and overview of other researchers' immunotherapy trials and laboratory studies; no new data collected)
• Who was studied: No study population of its own. The editorial discussed published and ongoing immunotherapy trials in mesothelioma patients, plus some mouse studies.
• Exposure: Not an asbestos exposure study. Treatments discussed were dendritic cell vaccination (with or without low-dose cyclophosphamide), a Listeria-based vaccine, CTLA-4 blockade (tremelimumab), CAR T cells, PD-1/PD-L1 inhibitors (pembrolizumab, nivolumab, avelumab), bevacizumab and inhibition of M2 macrophages.
• Main results:
  • Cited trial (2010, not this article's own data): ten mesothelioma patients received dendritic cell vaccination after chemotherapy. Nine showed a significant increase in peripheral blood mononuclear cells, four showed increased cytotoxic activity against their own tumor cells, and the vaccination was well tolerated.
  • Cited DETERMINE trial: a placebo-controlled Phase IIB study of tremelimumab given as second- and third-line treatment in 571 patients with advanced mesothelioma showed no survival benefit.
  • The editorial's authors reported having seen a response in one patient taking part in the DETERMINE trial.
  • Cited Keynote 28 Phase IB trial (pembrolizumab, mesothelioma patients with PD-L1 of 1% or more): disease control rate of 72% and objective response rate of 20%.
  • Cited Keynote 28 trial: median overall survival was 18 months.
  • Cited NivoMes (nivolumab) and JAVELIN (avelumab) trials, without PD-L1 selection: disease control rate of approximately 50%, and overall response rates of 28% (NivoMes) and 9.4% (JAVELIN).
  • Cited mouse model: CAR T cells given into the pleural space needed a 30-fold lower dose to eradicate pleural tumors than CAR T cells given intravenously.
• The authors' conclusion: The authors concluded that most mesothelioma tumors are noninflamed with low T-cell infiltration. In their view, treatment should be tuned to the missing step(s) in the cancer immunity cycle, combination treatment may add value, and immunotherapy may prove to be a viable option for mesothelioma patients.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Immunotherapy, Mesothelioma, Pemetrexed (Alimta), Pleural Mesothelioma, Bevacizumab, Lung Cancer, Tumor Microenvironment, Tremelimumab.

Related studies

• Dendritic cell-based immunotherapy in mesothelioma — R. Cornelissen, L.A. Lievense, et al. (2012)
• Precision immunotherapy; dynamics in the cellular profile of pleural effusions in malignant mesothelioma patients — L.A. Lievense, K. Bezemer, et al. (2017)
• Multimodality treatment of malignant pleural mesothelioma with or without immunotherapy: does it change anything? — M. Lucchi, A. Picchi, et al. (2010)
• New roads open up for implementing immunotherapy in mesothelioma — R. Cornelissen, M.E. Heuvers, et al. (2012)
• Mesothelin Immunotherapy for Cancer: Ready for Prime Time? — R. Hassan, A. Thomas, et al. (2016)
• T cell receptor repertoire characteristics both before and following immunotherapy correlate with clinical response in mesothelioma — H. Vroman, G. Balzaretti, et al. (2020)

Browse more research in Future Oncology, or return to medical research.