Immunotherapy in malignant pleural mesothelioma: a review of literature data

Our plain-English summary of Immunotherapy in malignant pleural mesothelioma: a review of literature data, by J. Menis, G. Pasello, J. Remon (Translational Lung Cancer Research, 2021).

The study

• Authors: J. Menis, G. Pasello, J. Remon
• Journal: Translational Lung Cancer Research
• Published: 2021;10(6):2988-3000
• Type of article: Review
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the pleural surface, associated with asbestos exposure, whose incidence is still growing in some areas of the world. MPM is still considered a rare and an orphan disease with an unchanged median overall survival (OS) ranging from 8 to 14 months and no treatment advances in the last 15 years both in local and advanced disease. In the recent years, chronic inflammation of the mesothelium together with local tumor suppression plays a major role in the malignant transformation. Also, significant heterogeneity in both tumor and the microenvironment is at the basis of MPM biology. Preclinical data have demonstrated the immunogenicity and the lack of an effective antitumor response by the immune system in MPM thus paving the way to the development of immune therapeutics in this disease. Still there is no clear evidence of any predictive biomarker so that, given the close interaction between the immune infiltrate and mesothelial cells, a number of trials are ongoing to investigate the role and prognostic value of the immune microenvironment. In this review we summarize the rationale for immune therapeutics development in MPM, as well as, the relevant literature and ongoing trials of immune checkpoint inhibitors (ICIs) and vaccines used as both first-line treatment and beyond.

2021 Translational Lung Cancer Research. All rights reserved.

In plain English

This article was a narrative review, not a new study. The authors summarized literature from 2000 to 2020 on immunotherapy for malignant pleural mesothelioma (MPM). The article describes MPM as clearly related to asbestos exposure, but it did not study asbestos exposure. The review covered the biological reasons for testing immune treatments, completed and ongoing trials of immune checkpoint inhibitors, and vaccine trials. Among the results the authors reported from other trials: a press release said the randomized CheckMate743 trial of nivolumab plus ipilimumab met its overall survival goal. In the randomized PROMISE trial, pembrolizumab did not give longer survival than chemotherapy. In the DETERMINE trial, tremelimumab did not significantly prolong survival compared with placebo. No safety or efficacy data were yet available for immune checkpoint inhibitors in surgically removable (resectable) MPM, because most of those trials were still ongoing. The authors wrote that, while CheckMate743 results were awaited, other randomized trials had shown no clear survival advantage. They pointed to small sample sizes and the exploratory nature of the trials. They concluded there is a promising biological rationale for evaluating checkpoint inhibitors, alone and combined, and cancer vaccines.

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: Narrative review of literature from 2000 to 2020
• Who was studied: Published and ongoing clinical trials, plus biological data, on immune checkpoint inhibitors and vaccines in patients with malignant pleural mesothelioma, in first-line and later treatment
• Exposure: Not an asbestos exposure study. The subject was immunotherapy treatment. The introduction states that MPM is related to asbestos exposure.
• Main results:
  • The authors judged that the preclinical data reviewed support testing immunotherapy in MPM
  • In the single-arm phase II DREAM trial (durvalumab plus first-line chemotherapy), 54 patients were enrolled. Progression-free survival at 6 months was 57% and the objective response rate was 48%.
  • According to a press release, the randomized phase 3 CheckMate743 trial (nivolumab plus ipilimumab versus platinum-pemetrexed chemotherapy in previously untreated MPM) achieved its primary overall survival endpoint
  • In the randomized PROMISE phase III trial (144 patients), second-line pembrolizumab did not give longer progression-free survival than chemotherapy (2.5 versus 3.4 months, HR 1.06, P=0.76). It also did not give longer overall survival (10.7 versus 11.7 months, HR 1.04, P=0.85).
  • In the randomized phase IIb DETERMINE trial, tremelimumab did not significantly prolong overall survival compared with placebo (7.7 and 7.3 months; HR 0.92, 95% CI 0.76 to 1.12)
  • In the MAPS2 phase 2 trial, the 12-week disease control rate was 40% in the nivolumab group and 52% in the nivolumab plus ipilimumab group
  • No safety or efficacy data were yet available for immune checkpoint inhibitors in resectable MPM, because most trials were still ongoing
  • Only one positive vaccine trial (autologous dendritic cell vaccination, PMR-MM-002) had been reported in MPM
  • While CheckMate743 results were awaited, the authors noted that no other randomized trial had shown a clear survival advantage for checkpoint inhibitors
• The authors' conclusion: The authors concluded there is a promising biological rationale for evaluating checkpoint inhibitors, alone and combined with chemotherapy and other biological agents, and also cancer vaccines
• Limitations the authors state:
  • Small sample sizes, methodological constraints and the exploratory nature of the trials reviewed
  • Trials did not consistently use the same response criteria or central imaging review
  • Most newly diagnosed patients do not meet clinical trial eligibility criteria, so trial results must be interpreted cautiously for everyday patients

Topics

Medical terms in this study, explained in our Lexicon: Immunotherapy, Pleural Mesothelioma, Asbestos Exposure, Median Overall Survival, Chronic Inflammation, Mesothelium, Malignant Transformation, Biomarker.

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