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Important Facts About Pleural Mesothelioma Immunotherapy
- Pleural mesothelioma immunotherapy is becoming a primary treatment method for this type of cancer, as it can be more effective than chemotherapy for some patients.
- The FDA-approved pleural mesothelioma immunotherapy drugs are Opdivo and Yervoy. Keytruda is also approved but only for a small percentage of cases of pleural mesothelioma.
- The main type of immunotherapy treatment used to treat pleural mesothelioma is called a “checkpoint inhibitor,” which helps the immune system identify cancer cells.
What is Pleural Mesothelioma Immunotherapy?
Immunotherapy is a type of pleural mesothelioma treatment that boosts the immune system’s response and ability to fight off cancer cells. Mesothelioma cancer cells attach to proteins and protein receptors to avoid the immune system and spread throughout the body undetected.
Immunotherapy helps the immune system properly identify and destroy mesothelioma cells without harming healthy tissue, which is one of the main differences between immunotherapy and chemotherapy.
How Does Immunotherapy Boost the Immune System?
The immune system is made up of several components. Each plays an important role in the immune system’s response to mesothelioma:
- Antigens – Foreign invaders, such as a virus, and could also refer to proteins on cancer cells (tumor antigens)
- T-cells – The soldiers of the immune system, tasked with attacking and eliminating cancer cells
- B-cells – Cells that produce antibodies to help defend against antigens
- Dendritic cells – Cells that download information about cancer cells or other diseases and deliver the information to T-cells.
- Antibodies – Proteins that mark cancer cells for the immune system to attack
The presence of antigens alerts the immune system and initiates an immune response. One of the tumor antigens for mesothelioma is a protein called mesothelin, which signals B-cells to begin producing antibodies.
Once the antibodies attach to the pleural mesothelioma cell, T-cells can identify and eliminate the diseased cells. Immunotherapy drugs send signals to B-cells to produce more antibodies or improve the T-cells’ response.
Side Effects of Pleural Mesothelioma Immunotherapy
Pleural mesothelioma immunotherapy is often preferred over pleural mesothelioma chemotherapy treatment due to less severe side effects. Immunotherapy side effects can be similar to chemotherapy, but they do not usually occur as often or as intense.
Side effects of pleural mesothelioma immunotherapy may include:
- Nausea and vomiting
- Body aches
- Loss of weight and appetite
- Feeling weak
- Skin rashes
Link Between Immunotherapy Side Effects and Improved Pleural Mesothelioma Survival
A team of researchers in Japan examined whether immune-related adverse effects (IRAEs) from the immunotherapy drug nivolumab (brand name Opdivo) led to longer survival for people with pleural mesothelioma. The study involved 11 patients, who all received Opdivo. The results are below:
- The disease control rate was 91% (10 out of 11 patients experienced a stall or shrinkage of their cancer).
- The median overall survival was 15 months.
- Progression-free survival was 6.8 months.
- Eight patients experienced IRAEs, and six had moderate side effects..
The six patients with moderate or more severe IRAEs had a progression-free survival of 13 months. The five patients with mild IRAEs or no IRAEs had a progression-free survival of 3.8 months.
The median overall survival was:
- Higher than one year for the group with moderate or more severe IRAEs
- 8.6 months for the group with mild or no IRAEs
This data hints that patients experiencing mild to moderate side effects could be evidence of immunotherapy’s effectiveness. Many side effects, including pain, can be managed with medications and palliative care.
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Checkpoint Inhibitor Immunotherapy for Pleural Mesothelioma
There are various types of immunotherapy treatments for pleural mesothelioma: checkpoint inhibitors, oncolytic viruses, adoptive cell therapy, monoclonal antibodies and more.
Checkpoint inhibitors are the primary method of immunotherapy used for pleural mesothelioma. This type of immunotherapy blocks mesothelioma cells from bypassing the T-cells in the immune system. By doing this, the immune system can properly identify and attack mesothelioma cells.
Mesothelioma cells contain specific proteins that interact with the T-cells’ proteins. Immune checkpoint inhibitors target these proteins.
PD-1/PD-L1 Checkpoint Inhibitors
PD-1 is an acronym for programmed cell death protein 1. It is a surface protein receptor on T-cells.
PD-L1 is an acronym for programmed death-ligand 1. It is a surface protein on mesothelioma cells.
When PD-1 binds with PD-L1, the T-cells do not properly identify mesothelioma cells. PD-1/PD-L1 checkpoint inhibitors block or break the protein binding and boost the T-cells’ ability to defend the body.
Examples of PD-1/PD-L1 checkpoint inhibitors include:
- Imfinzi, the brand name for durvalumab
- Keytruda, brand name for pembrolizumab
- Opdivo, brand name for nivolumab
CTLA-4/B7 Checkpoint Inhibitors
CTLA-4 is an immune cell receptor, while B7 is a mesothelioma cell protein. When these two bind, they inhibit the immune system’s ability to properly fight off infection. CTLA-4/B7 checkpoint inhibitors act as a wall between the two and boosts the T-cells defense.
The main example of a CTLA-4/B7 checkpoint inhibitor is Yervoy, the brand name for ipilimumab.
Opdivo and Yervoy: Immunotherapy Drugs for Pleural Mesothelioma
As previously mentioned, Opdivo and Yervoy are checkpoint inhibitor immunotherapy drugs. These are the most commonly used pleural mesothelioma immunotherapy drugs.
The FDA approved the use of Opdivo and Yervoy for unresectable cases of pleural mesothelioma in 2020. Unresectable cases of pleural mesothelioma refers to cases where surgery is not an option, which usually occurs in later-stage pleural mesothelioma patients (stage 3 or 4).
Opdivo and Yervoy work best when paired together. The immunotherapy treatments together target both the PD-1/PD-L1 and CTLA-4/B7 connections, which can address two of the ways pleural mesothelioma cells avoid the immune system. The dual-treatment method makes Opdivo and Yervoy more effective than if they were used individually.
Pleural Mesothelioma Survival Rates with Opdivo and Yervoy
A groundbreaking clinical trial, called Checkmate-743, studied the effects of Opdivo and Yervoy for malignant pleural mesothelioma versus chemotherapy for this cancer. The trial included 605 patients, with half of the participants receiving the Opdivo-Yervoy combination and the other half receiving chemotherapy.
The results were:
- 18.1 months median survival for the Opdivo and Yervoy group
- 14.1 months median survival for the chemotherapy group
- 40.8% 2-year survival for the Opdivo and Yervoy patients
- 27% 2-year survival for the chemotherapy patients
- 23% 3-year survival for the patients receiving Opdivo and Yervoy
- 15% 3-year survival for the patients receiving chemotherapy
Researchers conducted a 3-year follow-up with participants and saw Opdivo and Yervoy had positive long-term effects against tumor growth. Patients had not received immunotherapy for one year. More than 25% of immunotherapy patients were still responding to treatment, which means their disease was actively shrinking. The chemotherapy group did not show any treatment response at the 3-year follow-up, meaning their mesothelioma was still growing.
Frequently Asked Questions About Pleural Mesothelioma Stages
Can Pleural Mesothelioma Be Treated With Immunotherapy?
Pleural mesothelioma can be treated with immunotherapy. There are a few FDA-approved immunotherapy drugs for pleural mesothelioma treatment, including Opdivo and Yervoy. This type of treatment is becoming more common. There is evidence to support immunotherapy often outperforms chemotherapy.
What Types of Immunotherapy Treatments Are Available to Pleural Mesothelioma Treatment?
There are several types of immunotherapy, but the primary one available to pleural mesothelioma patients is called immune checkpoint inhibitors. This type of immunotherapy is the most common one used to treat patients with pleural mesothelioma. Examples of checkpoint inhibitors include Opdivo and Yervoy.
What Are the Side Effects of Pleural Mesothelioma Immunotherapy?
Pleural mesothelioma immunotherapy side effects may include nausea, vomiting, body aches, dizziness, fatigue, loss of weight and appetite, feeling weak and skin rashes. Some of these side effects of pleural mesothelioma immunotherapy are similar to chemotherapy side effects – although usually not as severe.
Sources & Author
- Types of Immunotherapy. WebMD. Retrieved from: https://www.webmd.com/cancer/immunotherapy-treatment-types. Accessed: 02/24/2021.
- Prognostic Role of Programmed Cell Death 1 Ligand 1 (PD-L1) in Resectable Pleural Mesothelioma. Annals of Thoracic Surgery. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/33248997/. Accessed: 12/14/2020.
- Ramucirumab–gemcitabine encouraging in second-line malignant pleural mesothelioma. Medwire News. Retrieved from: https://www.medwirenews.com/oncology/respiratory/ramucirumab-gemcitabine-malignant-pleural-mesothelioma/18096212. Accessed: 06/24/2020.
- Durvalumab added to standard chemotherapy improved overall survival in mesothelioma. American Association for the Advancement of Science. Retrieved from: https://eurekalert.org/pub_releases/2020-05/ecrg-dat052020.php. Accessed: 05/21/2020.
- FDA Approves Drug Combination for Treating Mesothelioma. U.S. Food and Drug Administration. Retrieved from: https://www.fda.gov/news-events/press-announcements/fda-approves-drug-combination-treating-mesothelioma. Accessed: 10/04/2020.
- Nivolumab Plus Ipilimumab Improves OS in Malignant Pleural Mesothelioma. Cancer Network. Retrieved from: https://www.cancernetwork.com/view/nivolumab-plus-ipilimumab-improves-os-in-malignant-pleural-mesothelioma. Accessed: 08/11/2020.
- Continued survival benefit in Targovax’s ONCOS-102 trial in mesothelioma at the 21-month follow-up. PRNewswire. Retrieved from: https://www.prnewswire.com/news-releases/continued-survival-benefit-in-targovaxs-oncos-102-trial-in-mesothelioma-at-the-21-month-follow-up-301233073.html. Accessed: 02/23/2021.
- Opdivo (nivolumab) Plus Yervoy (ipilimumab) Demonstrates Durable Overall Survival at Three Years Compared to Chemotherapy in First-Line Unresectable Malignant Pleural Mesothelioma in Phase 3 CheckMate -743 Trial. BusinessWire. Retrieved from: https://www.businesswire.com/news/home/20210913005059/en/Opdivo-nivolumab-Plus-Yervoy-ipilimumab-Demonstrates-Durable-Overall-Survival-at-Three-Years-Compared-to-Chemotherapy-in-First-Line-Unresectable-Malignant-Pleural-Mesothelioma-in-Phase-3-CheckMate–743-Trial. Accessed: 09/14/2021.
- Multimodal Therapy Survival in Malignant Pleural Mesothelioma Patients. Physician’s Weekly. Retrieved from: https://www.physiciansweekly.com/multimodal-therapy-survival-in-malignant-pleural-mesothelioma-patients. Accessed: 12/12/2022.
- Efficacy and Adverse Events of Apatinib Salvage Treatment for Refractory Diffuse Malignant Peritoneal Mesothelioma: A Pilot Study. Frontiers in Oncology. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/35847956/. Accessed: 09/28/2022.
- Preoperative immunotherapy for mesothelioma shows favorable outcomes. Baylor College of Medicine. Retrieved from: https://www.bcm.edu/news/preoperative-immunotherapy-for-mesothelioma-shows-favorable-outcomes. Accessed: 12/14/2022.