Immunotherapy is an emerging treatment option for malignant pleural mesothelioma. As a novel therapy, immunotherapy drugs may serve as an alternative to traditional therapies for some individuals. They work by stimulating the immune system to target and kill cancer cells. One mechanism by which these drugs work is by inhibiting PD-1 and PD-L1, a receptor and protein found on T-cells, one of the body’s primary cancer-fighting and cancer-killing cells. 

How PD-1 & PD-L1 Inhibitor Drugs Work

PD-1 inhibitor drugs work by inhibiting the PD-1 receptor found on T-cells. This receptor is like an “off” switch. It prevents T-cells from fighting and killing other cells, including cancer cells. By inhibiting PD-1, these drugs activate the immune system to function at a higher level. Researchers have found that PD-1 inhibitor drugs work best when combined with drugs that inhibit CTLA-4, a receptor similar to PD-1.¹ 

PD-L1 inhibitor drugs work to inhibit the protein, PD-L1, which activates PD-1. As of yet, no PD-L1 inhibitor drugs have been approved to treat malignant pleural mesothelioma.

Examples of PD-1 Inhibitor and CTLA-4 Inhibitor Drugs

PD-1 inhibitor drugs used to treat malignant pleural mesothelioma include

• Opdivo, also known as nivolumab
• Keytruda, also known as pembrolizumab

Opdivo is the only FDA-approved PD-1 inhibitor drug for malignant pleural mesothelioma. It was approved by the U.S. Food and Drug Administration on October 2, 2020, to be used in combination with Yervoy, a CTLA-4 inhibitor drug, as first-line therapy for unresectable malignant pleural mesothelioma. The clinical trial that supported its use found Opdivo with Yervoy to be significantly more effective than chemotherapy in improving overall survival.² The results of another clinical trial suggest that Opdivo with Yervoy is also effective in treating relapsed malignant pleural mesothelioma.³

How Opdivo Is Used to Treat Mesothelioma

Opdivo is commonly used in a multimodal approach, meaning it is combined with other immunotherapy drugs, like Yervoy, and other cancer therapies such as surgery, chemotherapy, and radiation. Combination treatment generally leads to better outcomes than what can be achieved with one drug or one kind of cancer therapy alone. 

Who Can Benefit from Opdivo

Because of the combined costs and toxicities of multimodal therapy, researchers are searching for clinical factors and biomarkers, characteristics unique to particular individuals with a specific disease state, to try to determine who can benefit most from immunotherapy drugs like Opdivo and Yervoy. Such biomarkers and clinical factors may include

• Tumor grade: microscopic features that characterize how quickly a tumor is likely to grow and spread
• Blood tests: blood samples commonly tested for tumor proteins, inflammatory markers, and gene mutations
• Disease recurrence
• Stage of disease: tumor size and spread
• Other health conditions
• Overall health status 

Further research is needed to develop targeted PD-1 inhibitor therapy, taking into account an individual’s unique clinical factors, biomarkers, and response to treatment. Such studies are critical in improving survival and quality of life for individuals with mesothelioma. With future research, we may even find a cure for the disease.