Written by: Devin Golden
Immunotherapy for Mesothelioma
Immunotherapy for mesothelioma is an emerging treatment option for this cancer. Immunotherapy drugs boost the immune system in various ways to destroy cancerous mesothelial cells.
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Important Facts About Immunotherapy for Mesothelioma
- In 2020, the U.S. Food and Drug Administration (FDA) approved Opdivo and Yervoy in tandem for unresectable cases of pleural mesothelioma.
- The FDA also approved Keytruda for specific cases of pleural mesothelioma.
- There are different types of immunotherapy drugs. Most are called “checkpoint inhibitors,” blocking cancer cells from evading the immune system.
- Researchers believe immunotherapy has a synergy with other treatments, such as radiation and virotherapy, and can boost each other’s effectiveness.
Immunotherapy Drugs Approved for Mesothelioma
The FDA in 2020 approved Opdivo and Yervoy for mesothelioma. The drugs must be used together and only for cases where surgery isn’t an option. Opdivo and Yervoy are brand names for the checkpoint inhibitor drugs nivolumab and ipilimumab, respectively.
Keytruda, another checkpoint inhibitor, is the brand name for pembrolizumab. The FDA approved it in cases with high amounts of a specific cancerous protein.
How to Get Immunotherapy for Mesothelioma
For patients interested in how to get mesothelioma immunotherapy treatment, here are three steps to receive this promising option:
Here’s how some immunotherapy drugs fight cancers like mesothelioma:
Look up the side effects and other information about FDA-approved immunotherapy drugs. Be aware of the regular effects so you can know what’s normal and what’s a cause for concern.
Ask your doctor about immunotherapy options offered at the hospital. Opdivo and Yervoy are FDA-approved and available at many cancer centers. Other institutions have clinical trials involving immunotherapy.
Contact a patient advocate for help finding a cancer center. If you don’t already have a mesothelioma specialist, reach out to our team. We can direct you to nearby cancer centers offering immunotherapy treatment.
Makeup of the Immune System
Your immune system has various components. Each plays a role in detecting and responding to mesothelioma and other cancers:
- Antigens – Foreign invaders, such as a virus, that also refer to proteins on cancer cells (tumor antigens)
- T-cells – The soldiers of the immune system, attacking and eliminating cancer cells
- B-cells – Cells that produce antibodies to help defend against antigens
- Antibodies – Proteins that mark cancer cells for the immune system to attack
- Lymphocytes – White blood cells consisting of immune system cells
The presence of antigens raises the immune system’s alarm. The primary tumor antigen for mesothelioma is a protein called mesothelin.
Mesothelin is the signal for B-cells to produce antibodies. Once they attach to mesothelin, T-cells should identify and kill the labeled diseased cells.
Immunotherapy can signal to B-cells to produce more antibodies or enhance T-cells against mesothelioma.
How Does Immunotherapy for Mesothelioma Help?
Immunotherapy enables the immune system to properly fight against unwanted intruders, such as cancer cells. Diseases like mesothelioma subdue or sidestep the immune system, allowing it to spread freely without inhibition. Immunotherapy helps the immune system actively target these diseases.
Here’s how some immunotherapy drugs fight cancers like mesothelioma:
Immune cells don’t recognize cancerous cells as a threat, which allows them to replicate and spread.
Immunotherapy attaches to or kills cancerous cells, which alarms the immune system.
The patient’s immune cells recognize cancerous antigens and target cells with similar antigens.
The patient’s immune cells seek out the remaining cancer cells, leaving healthy cells unharmed.
Other immunotherapy drugs add lab-altered T-cells or lab-produced antibodies to aid the immune system.
Fewer Side Effects for Patients
Immunotherapy for mesothelioma has similar side effects to chemotherapy, but they occur less often and less severely. Immunotherapy can make patients fatigued, nauseous or dizzy. Other side effects are weakness, body aches and skin rashes.
Doctors often compare immunotherapy to chemotherapy, hoping to determine which is best for both safety and survival. Most studies favor mesothelioma immunotherapy over chemotherapy.
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Types of Immunotherapy for Mesothelioma
There are four main types of immunotherapy for mesothelioma: checkpoint inhibitors, oncolytic viruses, adoptive cell therapy and monoclonal antibodies. These types are split into how the drugs stimulate the immune system: actively or passively.
Active immunotherapy uses drugs or viruses to establish a proper immune response. Passive immunotherapy adds laboratory immune cells to aid the body against cancer.
Checkpoint inhibitors block mesothelioma cells from subduing the immune system T-cells. Blocking the mesothelioma cells allows the immune system to react properly to the presence of mesothelioma. This is a type of active immunotherapy.
Mesothelioma cells have proteins that interact with T-cells’ proteins. The most familiar to doctors and researchers are PD-L1 and PD-1.
PD-1/PD-L1 Checkpoint Inhibitors
PD-L1, the acronym for programmed death-ligand 1, is a surface protein on mesothelioma cells. PD-1, the acronym for programmed cell death protein 1, is a surface protein receptor on T-cells.
When PD-1 binds with PD-L1, the T-cells ignore mesothelioma cells. PD-1/PD-L1 checkpoint inhibitors act as a wall between the protein and receptor. The drugs prevent, or break, the binding and allow T-cells to defend the body.
Examples of PD-1/PD-L1 checkpoint inhibitors include:
- Keytruda, brand name for pembrolizumab
- Opdivo, brand name for nivolumab
- Imfinzi, the brand name for durvalumab
CTLA-4/B7 Checkpoint Inhibitors
Another example is a CTLA-4/B7 checkpoint inhibitor. These drugs block CTLA-4 (immune cell receptor) and B7 (mesothelioma cell protein).
The main example is Yervoy, the brand name for ipilimumab.
Oncolytic viruses deliver an antigen into the body to elicit an immune reaction. This is a combination of virotherapy and immunotherapy, and it’s another form of active immunotherapy.
Oncolytic viruses work like regular viruses except they don’t attack healthy cells. They kill only diseased cells, which release antigens that cause an immune response.
An example is mesothelioma oncolytic virus ONCOS-102. The therapy breaks up mesothelioma cells, which releases antigens. The virus then requests for the T-cells to swarm to the site of the cancer.
Adoptive Cell Therapy
Adoptive cell therapy alters immune system cells in a laboratory to better fight cancers like mesothelioma. Usually immunotherapy experts will alter T-cells, which are the soldiers protecting the body from diseases.
The most familiar adoptive cell therapy for mesothelioma is CAR T-cell therapy. CAR is an acronym for chimeric antigen receptor. This form of immunotherapy uses lab-created receptors to target mesothelioma specifically.
IcasM28z is an example of adoptive cell therapy. The CAR T-cells target mesothelin, a protein found on the surface of mesothelioma cells.
Monoclonal antibodies are lab-generated antibodies inserted into the body to fight mesothelioma. It’s another form of passive immunotherapy.
They stick to mesothelioma receptors and partner with the immune system to fight the disease. Examples of monoclonal antibodies are LMB-100, ramucirumab and anetumab ravtansine.
Top Mesothelioma Immunotherapy Drugs
The top immunotherapy drugs for mesothelioma are checkpoint inhibitors. Other immunotherapy drugs include oncolytic viruses and adoptive cell therapies and monoclonal antibodies.
The top immunotherapy drugs for mesothelioma are:
Nivolumab (Opdivo), a PD-1/PD-L1 checkpoint inhibitor (FDA-approved)
Ipilimumab (Yervoy), a CTLA-4/B7 checkpoint inhibitor (FDA-approved)
Pembrolizumab (Keytruda), a PD-1/PD-L1 checkpoint inhibitor (limited FDA approval)
ONCOS-102, an oncolytic virus (close to FDA approval)
Ramucirumab, monoclonal antibody
IcasM28z, an adoptive CAR T-cell therapy
LMB-100, a monoclonal antibody
Durvalumab (Imfinzi), a PD-1/PD-L1 checkpoint inhibitor
Anetumab ravtansine, a monoclonal antibody
Each is either FDA-approved or part of mesothelioma clinical trials.
Survival Rates for Mesothelioma Immunotherapy
FDA-approved mesothelioma immunotherapy options range in median survival from 18-20 months. Survival variables include the type of immunotherapy, the patient’s cell type and stage, and whether the drug is paired with other treatment options.
The survival benefit and safety are the two measurements the FDA looks for in applications for approval. Most importantly, immunotherapy (with or without other treatments) consistently outperforms chemotherapy for mesothelioma:
- Opdivo and Yervoy had a median survival of 18.1 months, which was better than chemotherapy (14.1 months).
- ONCOS-102 with chemotherapy posted a median survival of 20.5, which is seven months better than just chemotherapy.
- Durvalumab plus chemotherapy had a median survival of 20 months, much better than chemotherapy on its own.
Immunotherapy in Multimodal Treatment for Mesothelioma
The FDA is considering immunotherapy as an alternative to chemotherapy, specifically for people who cannot have surgery. However, studies continue to investigate whether immunotherapy works as part of multimodal treatment for mesothelioma.
Multimodal treatment refers to using multiple types of therapy. As a multimodal therapy, immunotherapy would pair with one or multiple of:
Immunotherapy and Mesothelioma Surgery
Ongoing clinical trials are testing immunotherapy before, after, or both before and after mesothelioma surgery. This is especially relevant for patients with a high amount of PD-L1 expression on their cancer cells.
Dr. Patrick Forde, of Johns Hopkins Hospital in Baltimore, Maryland, is running a study using Opdivo and Yervoy six weeks before surgery. Patients can resume immunotherapy weeks after surgery if they choose.
Immunotherapy and Mesothelioma Chemotherapy
Doctors often pair investigative immunotherapy drugs with mesothelioma chemotherapy in clinical studies. The combination of cancer-killing drugs with immune-enhancing drugs attacks mesothelioma on two fronts.
Immunotherapy and Mesothelioma Radiation Therapy
Many doctors feel immunotherapy and mesothelioma radiation therapy can have a synergetic relationship. Radiation inflames the tissue where cancer exists, which can elicit an immune response. Immunotherapy helps make the responding T-cells prepared to fight.
Radiation also can partially kill tumors, clumps of diseased cells, which then release antigens. These antigens are what the T-cells look for, and immunotherapy can amplify the immune system’s ability.
Common Questions About Immunotherapy for Mesothelioma
Does immunotherapy work for mesothelioma?
Immunotherapy is one of the emerging treatment options for mesothelioma patients who cannot undergo surgery. The therapy helps the immune system locate mesothelioma cells and attack the tumors, which slows the disease’s progress and extends the patient’s life. Numerous studies report survival times of multiple years thanks to immunotherapy.
What types of immunotherapy are available to mesothelioma patients?
The most popular type of immunotherapy for mesothelioma is a checkpoint inhibitor. This blocks two protein receptors from linking, which strengthens the immune system. Examples of checkpoint inhibitor drugs are Keytruda, Opdivo and Yervoy. Another example of immunotherapy is giving the body a virus, or something similar, to activate the immune system.
Is Keytruda available for mesothelioma?
The FDA recently approved Keytruda for specific cases of pleural mesothelioma. The drug is for patients who have an unresectable, malignant disease and meet a specific threshold of PD-L1 tumor burden. PD-L1 is a cancerous protein that links with PD-1, an immune system receptor, and inhibits the immune system response. Keytruda blocks the connection.
How can I get immunotherapy to treat my mesothelioma?
The FDA recently approved multiple forms of immunotherapy for mesothelioma, making the treatment more easily accessible through cancer centers. The combination of Opdivo and Yervoy is available to patients who cannot undergo surgery. Patients who don’t meet the FDA’s criteria can enroll in clinical trials to receive immunotherapy on an experimental basis.
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.