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.
Pleural mesothelioma (PM) is a rare malignancy arising from the pleural surface and is associated with a poor prognosis. The primary risk factor for development of PM is inhalational asbestos exposure, often via occupational or environmental means, with a prolonged period of at least 15 and on average 30–40 years from the time of exposure to diagnosis. In 2020, over 30,000 new cases of PM were identified globally, with the worldwide incidence of PM decreasing in recent years, most likely due to the increased regulations surrounding asbestos. However, the incidence in several countries, specifically those with less restrictive regulation of asbestos use, is predicted to increase in the coming years.
In 2021, the World Health Organization (WHO) fifth edition classified PM into three histologic subtypes: epithelioid, sarcomatoid, and biphasic. Epithelioid mesothelioma (EM) is the most common subtype, representing about 60% of all mesothelioma diagnoses. The historical median survival of patients diagnosed with mesothelioma is associated with these subtypes, ranging from an average of 19 months for patients with epithelioid disease undergoing surgical resection to 4 months for those with sarcomatoid disease. Despite advances in oncologic care, in 2018, the relative 5-year overall survival for all patients was around 14.6%.
Historically, platinum-based chemotherapy has been the standard of care for the systemic treatment of mesothelioma, with limited improvement in outcomes with the addition of novel agents and maintenance therapies. More recently, however, the use of immune-checkpoint inhibitors has been shown to significantly improve outcomes for many patients. This review will detail challenges and nuances in the diagnosis of mesothelioma, as well as provide an overview of outcomes of key mesothelioma clinical trials with a focus on the current and future role of immunotherapy and discussion of novel strategies for treatment. [Footnotes omitted.]
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