Immunotherapy of mesothelioma: the evolving change of a long-standing therapeutic dream

Our plain-English summary of Immunotherapy of mesothelioma: the evolving change of a long-standing therapeutic dream, by L. Calabrò, G. Bronte, F. Grosso, et al (Frontiers in Immunology, 2023).

The study

• Authors: L. Calabrò, G. Bronte, F. Grosso, L. Cerbone, A. Delmonte, F. Nicolini, M. Mazza, A.M. Di Giacomo, A. Covre, M.F. Lofiego, L. Crinò, M. Maio
• Journal: Frontiers in Immunology
• Published: 2023;14:1333661
• Type of article: Review
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Pleural mesothelioma (PM) is an aggressive and rare disease, characterized by a very poor prognosis. For almost two decades, the world standard treatment regimen for unresectable PM has consisted of a platinum-based drug plus pemetrexed, leading to an overall survival of approximately 12 months. The dramatic therapeutic scenario of PM has recently changed with the entry into the clinic of immune checkpoint inhibition, which has proven to be an effective approach to improve the survival of PM patients. The aim of the present review is to provide a comprehensive overview of the most promising immunotherapeutic-based strategies currently under investigation for advanced PM.

Copyright © 2024 Calabrò, Bronte, Grosso, Cerbone, Delmonte, Nicolini, Mazza, Di Giacomo, Covre, Lofiego, Crinò and Maio.

In plain English

This article was a review, not a new study. The authors surveyed immunotherapy approaches for pleural mesothelioma: immune checkpoint inhibitors, epigenetic drugs, dendritic cell vaccines and CAR T cells. They also described the immune cells found in these tumors. They noted that standard platinum plus pemetrexed chemotherapy gave median overall survival of 12 to 14 months. Among reviewed trials, CheckMate 743, with 605 first-line patients, reported median overall survival of 18.1 months with nivolumab plus ipilimumab versus 14.1 months with chemotherapy. The difference was larger in non-epithelioid tumors (16.5 versus 8.8 months). The DETERMINE trial, with 568 previously treated pleural or peritoneal mesothelioma patients, found no survival improvement with tremelimumab over placebo (7.7 versus 7.3 months). The CONFIRM trial, with 332 second- or third-line patients, reported median overall survival of 9.2 versus 6.6 months with nivolumab versus placebo. The review did not study asbestos exposure, but cited an earlier study that found tumor DNA methylation profiles associated with lung asbestos burden and clinical outcome. The authors concluded that dual checkpoint inhibition marked a therapeutic paradigm shift, but that much remains to be done to overcome immune resistance.

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 published and ongoing clinical trials and laboratory studies of immunotherapy for pleural mesothelioma
• Who was studied: No new patients were studied. The review covered trials in pleural mesothelioma patients; some reviewed trials (MESOT-TREM, DETERMINE) also included peritoneal mesothelioma patients.
• Exposure: The review did not study asbestos exposure. It reviewed treatments: immune checkpoint inhibitors (tremelimumab, ipilimumab, nivolumab, pembrolizumab, durvalumab), epigenetic drugs, dendritic cell vaccination and CAR T cells. Asbestos came up in two ways. The authors described prolonged inflammation from asbestos fibers as part of how the disease develops. They also cited an earlier study (Christensen and colleagues) that linked DNA methylation profiles to lung asbestos burden.
• Main results:
  • As background, the authors stated that patients treated with standard cisplatin or carboplatin plus pemetrexed had median overall survival between 12 and 14 months.
  • Reviewed trial CheckMate 743 (605 first-line pleural mesothelioma patients) reported median overall survival of 18.1 months with nivolumab plus ipilimumab versus 14.1 months with platinum-based chemotherapy (HR 0.74, 96.6% CI 0.6 to 0.9, p=0.002).
  • In CheckMate 743, patients with non-epithelioid histology had median overall survival of 16.5 months with dual checkpoint inhibition versus 8.8 months with chemotherapy (HR 0.46, 95% CI 0.3 to 0.7).
  • Reviewed trial DETERMINE (568 pre-treated pleural or peritoneal mesothelioma patients) found that tremelimumab did not improve overall survival compared with placebo (7.7 and 7.3 months; HR 0.92; P = 0.41).
  • Reviewed trial CONFIRM (332 second- or third-line patients) reported median overall survival of 9.2 months with nivolumab versus 6.6 months with placebo (HR 0.72; 95% CI 0.55 to 0.94; P = 0.018).
  • In CONFIRM, the survival improvement was seen in patients with epithelioid histology (9.4 vs. 6.6 months; HR 0.71; 95% CI 0.53 to 0.95) but not in those with non-epithelioid histology.
  • Reviewed trial PROMISE-Meso (144 pre-treated patients) found no improvement in median overall survival with pembrolizumab versus chemotherapy (10.7 vs. 12.4 months).
  • The phase III part of the reviewed IND.227 trial reported overall survival of 17.3 months with pembrolizumab plus chemotherapy versus 16.1 months with chemotherapy alone (HR=0.79).
  • A reviewed phase I study of anti-mesothelin CAR T cells combined with pembrolizumab in pleural mesothelioma patients reported an objective response rate of 63% and median overall survival of 23.9 months.
  • An earlier study cited in the review (Christensen and colleagues) found that the DNA methylation profile of pleural mesothelioma was significantly associated with lung asbestos burden and clinical outcome.
• The authors' conclusion: The authors concluded that better knowledge of tumor immunology had led to a therapeutic paradigm shift in pleural mesothelioma. They pointed to the approval of the first chemotherapy-free regimen, nivolumab plus ipilimumab. They added that much remains to be gained in overcoming immune resistance, and that new strategies are under investigation.

Topics

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

Medical terms in this study, explained in our Lexicon: Immunotherapy, Mesothelioma, Standing, Pleural Mesothelioma, Prognosis, Unresectable, Pemetrexed (Alimta), Overall Survival.

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