Immune checkpoint blockade in malignant mesothelioma: A novel therapeutic strategy against a deadly disease?

Our plain-English summary of Immune checkpoint blockade in malignant mesothelioma: A novel therapeutic strategy against a deadly disease?, by L. Calabrò, M. Maio (Oncoimmunology, 2014).

The study

• Authors: L. Calabrò, M. Maio
• Journal: Oncoimmunology
• Published: 2014;3(1):e27482
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Monoclonal antibodies that target immune checkpoints are undoubtedly changing the therapeutic landscape of different human malignancies. Here we comment on the effects of blocking cytotoxic T lymphocyte-associated protein 4 (CTLA4) by means of the monoclonal antibody tremelimumab in patients with refractory malignant mesothelioma, a deadly disease with no effective therapeutic options.

In plain English

This article was a short commentary ("Author's View") in which the authors discussed their own earlier clinical trial, MESOT-TREM-2008. Its preliminary results had already been published in The Lancet Oncology. The trial tested tremelimumab, an antibody that blocks an immune-system protein called CTLA4. Patients had malignant mesothelioma that could not be removed by surgery and that had not been controlled by first-line platinum-containing chemotherapy. The trial's main goal, the objective response rate, was not met. Of 29 patients treated, 2 had a durable partial response and 7 had prolonged disease stabilization, a disease control rate of 31%. In one patient the disease first progressed and then showed a long-lasting partial response. The 1- and 2-year survival rates were 48.3% and 36.7%, which the authors said compared quite favorably with available data. An early rise in circulating CD4+ICOS+ T lymphocytes during treatment predicted improved survival, but levels before treatment did not identify who would do well. The authors noted the small cohort and called the evidence initial and, in their view, highly encouraging.

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: Commentary (Author's View) by the authors on their own previously published clinical trial (MESOT-TREM-2008); no new data beyond that trial's preliminary results
• Who was studied: Patients with unresectable malignant mesothelioma (MM) whose disease had failed a first-line platinum-containing chemotherapy regimen; 29 patients were treated with tremelimumab. The figure shows a patient with malignant pleural mesothelioma.
• Exposure: Treatment with tremelimumab, a monoclonal antibody that blocks CTLA4. The article does not discuss asbestos or fiber exposure.
• Main results:
  • The trial's primary endpoint, objective response rate, was not met
  • Of 29 patients treated with tremelimumab, 2 had a durable partial response and 7 had prolonged disease stabilization; disease control rate 31%
  • One patient had initial disease progression followed by a long-lasting partial response
  • Long-lasting stable disease in 24% of enrolled MM patients
  • 1-year survival 48.3% and 2-year survival 36.7% among treated patients, which the authors said compared quite favorably with available data for MM patients
  • An increase in circulating CD4+ICOS+ T lymphocytes very early in treatment predicted improved survival
  • Levels of CD4+ICOS+ T lymphocytes before therapy did not identify patients who would have a favorable outcome
• The authors' conclusion: The authors concluded that the MESOT-TREM-2008 study provided initial and, in their view, highly encouraging evidence of clinical and immunological activity of tremelimumab in pre-treated MM patients. They launched a further trial (MESOT-TREM-2012) to test a more intensive schedule.
• Limitations the authors state:
  • Small number of patients in the trial

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Monoclonal Antibody, Tremelimumab.

Related studies

• Recent Advances of Immune Checkpoint Inhibition and Potential for (Combined) TIGIT Blockade as a New Strategy for Malignant Pleural Mesothelioma — S. Rovers, A. Janssens, et al. (2022)
• Splicing modulation as novel therapeutic strategy against diffuse malignant peritoneal mesothelioma — R. Sciarrillo, A. Wojtuszkiewicz, et al. (2019)
• Inhibition of the spindle assembly checkpoint kinase Mps-1 as a novel therapeutic strategy in malignant mesothelioma — A. Szymiczek, M. Carbone, et al. (2017)
• Success of Checkpoint Blockade Paves the Way for Novel Immune Therapy in Malignant Pleural Mesothelioma — L. Rondon, R. Fu, et al. (2023)
• Immune checkpoint blockade in malignant mesothelioma — L. Calabrò, M. Maio (2015)
• Immune checkpoint blockade therapy of mesothelioma: a clinical and radiological challenge — L. Calabrò, A. Morra, et al. (2018)

Browse more research in Oncoimmunology, or return to medical research.