Immunotherapy for Treatment of Pleural Mesothelioma: Current and Emerging Therapeutic Strategies

Our plain-English summary of Immunotherapy for Treatment of Pleural Mesothelioma: Current and Emerging Therapeutic Strategies, by L. Chiec, D.S. Bruno (International Journal of Molecular Sciences, 2024).

The study

• Authors: L. Chiec, D.S. Bruno
• Journal: International Journal of Molecular Sciences
• Published: 2024;25(19)
• Type of article: Review
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Pleural mesothelioma is a rare malignancy associated with asbestos exposure and very poor prognosis, with a 5-year overall survival of 12%. Outcomes may vary according to stage at time of diagnosis and histologic subtype. Most recently, clinical trials utilizing dual checkpoint inhibitor regimens and chemotherapy in combination with immune oncologic agents have demonstrated impactful changes in outcomes. In this article, we review studies that have led to the successful implementation of immunotherapy in clinical practice for the treatment of this disease and highlight ongoing clinical trials exploring the use of different immunotherapy strategies for the treatment of pleural mesothelioma. We also discuss the challenges of immunotherapy-based approaches in the context of mesothelioma and future strategies currently being investigated to overcome them.

In plain English

This article was a narrative review, not a new study. The authors summarized published and ongoing clinical trials of treatment for pleural mesothelioma, focusing on immunotherapy (treatments using the immune system, including drugs, engineered immune cells and cell vaccines). They did not study asbestos exposure. Asbestos appeared only in the background, as the primary risk factor for the disease. As the review reported it, the CheckMate 743 trial randomized 605 patients and found a median overall survival of 18.1 months with nivolumab plus ipilimumab, compared with 14.1 months with chemotherapy. For patients with non-epithelioid tumors in that trial, the figures were 18.1 and 8.5 months. Other reviewed trials gave mixed results. In DETERMINE, tremelimumab alone showed no significant survival difference from placebo. In CONFIRM, nivolumab showed a significant survival improvement over placebo after earlier chemotherapy. The authors concluded that immunotherapy is a safe and established approach for advanced pleural mesothelioma. In their view, dual checkpoint inhibition should be offered as the first treatment, especially for non-epithelioid histology. They added that PD-L1 has so far been a less consistent biomarker.

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 clinical trials of treatment for pleural mesothelioma, with a focus on immunotherapy
• Who was studied: No patients were studied directly. The review covered published and ongoing clinical trials in patients with pleural mesothelioma (some trials also included peritoneal mesothelioma), in previously treated, first-line, and resectable (early-stage) disease.
• Exposure: Not an asbestos exposure study. Asbestos is mentioned only in the background as the primary risk factor. The interventions reviewed were treatments: immune checkpoint inhibitors (tremelimumab, pembrolizumab, nivolumab, avelumab, ipilimumab, durvalumab, atezolizumab), alone or with chemotherapy, plus cellular therapies (CAR-T, dendritic cell vaccines) and other strategies.
• Main results:
  • As reported in this review, the CheckMate 743 trial (605 patients with unresectable mesothelioma) found a median overall survival of 14.1 months with standard chemotherapy and 18.1 months with nivolumab plus ipilimumab (HR 0.74, 96.6% CI 0.60–0.91, p = 0.002).
  • In CheckMate 743, as reported here, median overall survival in non-epithelioid patients was 18.1 months with immunotherapy and 8.5 months with chemotherapy.
  • As reported here, the DETERMINE trial (571 patients with pleural and peritoneal mesothelioma, previously treated) found no significant difference in median overall survival between tremelimumab and placebo (7.7 vs. 7.3 months, HR 0.92, 95% CI 0.76–1.12, p = 0.41).
  • As reported here, the CONFIRM trial (n = 332, after platinum-based chemotherapy) found a significant overall survival improvement with nivolumab compared with placebo: 9.2 vs 6.6 months (HR 0.72, 95% CI 0.55–0.94, p = 0.02).
  • As reported here, the IND227 trial (440 patients) found a median overall survival of 17.3 months with first-line pembrolizumab plus chemotherapy, compared with 16.1 months with chemotherapy alone (HR 0.79, 95% CI 0.64–0.98, p = 0.0324).
  • As reported here, the BEAT-meso trial (400 patients) found a median overall survival of 20.5 months with atezolizumab added to chemotherapy plus bevacizumab, compared with 18.1 months in the control arm (HR 0.84, 95% CI 0.66–1.06, p = 0.14). This difference was not statistically significant.
• The authors' conclusion: The authors concluded that immunotherapy is a safe and established approach in advanced pleural mesothelioma. In their view, dual checkpoint inhibition should be offered first-line, especially for non-epithelioid histology. They also stated that PD-L1 has so far been a less consistent biomarker.

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, Pleural Mesothelioma, Asbestos Exposure, Prognosis, Overall Survival, Histological Subtype, Clinical Trial, checkpoint inhibitors.

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