01. What Is Immunotherapy?
What Is Immunotherapy for Mesothelioma?
Mesothelioma immunotherapy is a type of treatment that uses the patient’s immune system to find and attack cancer cells. Many types of immunotherapy are used to treat mesothelioma and other cancers. For mesothelioma, researchers have focused on a few types of immunotherapy, including:
- Cancer vaccines
- CAR T-cell therapy
- Immune checkpoint inhibitors
- Monoclonal antibodies
- Oncolytic viruses
The most promising immunotherapy treatment for mesothelioma has been immune checkpoint inhibitors. These new drugs have extended survival and improved quality of life for mesothelioma patients. Checkpoint inhibitors also tend to be less toxic than chemotherapy drugs.
The United States Food and Drug Administration (FDA) has approved some immunotherapy drugs for mesothelioma. But patient eligibility depends on many factors. Patients can talk to their doctors to see if immunotherapy is right for them.
FDA-Approved Mesothelioma Immunotherapy
Some immunotherapy treatments are FDA-approved for mesothelioma. Others have FDA approval to treat tumors with characteristics found in some mesotheliomas. FDA-approved immunotherapies for mesothelioma include:
- Opdivo® + Yervoy®: Opdivo (nivolumab) has FDA approval to treat inoperable malignant pleural mesothelioma when combined with Yervoy (ipilimumab). In one pleural mesothelioma study, this combination improved overall survival versus chemotherapy. Study patients treated with the combination had a median survival of 18.1 months.
- Keytruda®: Keytruda (pembrolizumab) is not approved specifically for mesothelioma. However, Keytruda is approved to treat tumors in the “tumor mutational burden-high” (TMB-H) category. If a patient’s mesothelioma tumor falls into this category, doctors can prescribe Keytruda as a treatment. In one study, the median overall survival was 18 months with Keytruda.
Clinical trials continue to test the efficacy of immunotherapy drugs against mesothelioma. Immunotherapy drugs currently in clinical trials include tremelimumab, Imfinzi® (durvalumab), Tecentriq® (atezolizumab) and Avastin® (bevacizumab).
02. Immunotherapy Benefits
Benefits of Immunotherapy for Mesothelioma
Researchers have found many benefits for mesothelioma patients who receive immunotherapy. These advantages include improvements to mesothelioma prognosis and quality of life. Benefits vary depending on the type of immunotherapy, the type of cancer and patient factors.
Some specific areas where researchers have observed benefits include:
- Preparation: Some immunotherapy drugs do not require pre-treatment preparations like certain chemotherapy drugs. For example, patients receiving pemetrexed chemotherapy get vitamin injections the week before treatment. Checkpoint inhibitors do not require this preparation.
- Quality of life: Research suggests that patients receiving immunotherapy may see quality-of-life benefits. In studies, patients receiving Opdivo and Yervoy experienced improved quality of life.
- Side effects: Immunotherapy can cause side effects, but they may not be as severe as chemotherapy and radiation. Common immunotherapy side effects include fatigue, muscle aches, fever, chills, dizziness and weakness.
- Survival: Some immunotherapies have improved survival rates versus other treatments. In one study, patients treated with Opdivo + Yervoy had a 1-year survival rate of 68%. Study patients treated with chemotherapy had a 1-year survival rate of 58%.
To learn more about potential immunotherapy benefits, mesothelioma patients should contact their doctor. Mesothelioma doctors can further explain the benefits relating to a patient’s individual case.
03. Immunotherapy Side Effects
Side Effects of Immunotherapy for Mesothelioma
Side effects are possible with immunotherapy as they are with any type of treatment. However, common immunotherapy treatments generally have less severe side effects than chemotherapy.
Side effects from immunotherapy vary depending on many factors. These include the type of immunotherapy, type of cancer and patient factors. Patients can discuss possible side effects with their doctor in advance of treatment.
Patients receiving immunotherapy may experience mild to severe side effects. According to one expert, immune checkpoint inhibitors cause side effects in about 5% – 10% of patients. Of those, only 1% – 2% may be life threatening. Commonly reported side effects for checkpoint inhibitors include fatigue and inflammation.
- Fatigue: Many cancer treatments cause fatigue. It may stem from the energy required to process the treatment. Cancer itself can also cause fatigue.
- Inflammation: This may occur because the immune system is working harder than normal. Patients may notice inflammation throughout their bodies as their powered-up immune system does its work. For example, patients receiving immune checkpoint inhibitors may have inflammation in their organs.
Some patients may have severe immune reactions, called immune-related adverse events (irAEs). They may have symptoms similar to autoimmune disorders.
Patients may experience irAEs when the immune system attacks healthy tissue. Some common irAEs include skin reactions and thyroid inflammation. Doctors can manage irAEs by pausing or stopping treatment. In some cases, the doctor may also prescribe corticosteroids or other immunosuppressants.
It is important for patients to consult their doctor if they notice any treatment reactions. Working with a doctor can help manage these side effects.
Did You Know?
04. How It Works
How Does Immunotherapy Work?
Immunotherapy works by empowering the immune system to recognize and attack cancer cells. Different types of immunotherapy use different immune system components to treat cancer.
In general, cancer cells are adept at avoiding immune system attacks. They commonly do this by exploiting immune checkpoints. These checkpoints normally allow immune cells to recognize and ignore healthy cells. But cancer cells can use immune checkpoints to pose as healthy cells and dodge immune cell attacks.
Checkpoint inhibitors block cancer cells from using immune checkpoints in this way. This allows the immune system to fight tumors.
Immunotherapy may extend patient life expectancy or relieve symptoms. If a doctor recommends immunotherapy for symptom relief alone, it may be considered a palliative treatment. Palliative care aims to relieve cancer symptoms and improve quality of life. For example, immunotherapy can be used to shrink a tumor. In turn, this may reduce pain from the tumor.
There are two main types of immunotherapy. They differ chiefly in how long they affect the body.
Active vs. Passive Immunotherapy
Active Immunotherapy: Active immunotherapy may evoke a lasting response through the use of immune memory. In some cases, this works a bit like vaccines. Immunotherapy can teach immune cells to recognize cancer cells. If the immune cells remember this lesson, the treatment may continue to work after it is initially administered.
Passive Immunotherapy: Passive immunotherapy evokes a short-term response. It commonly introduces synthetic immune proteins to help fight cancer. The synthetic proteins can trigger an immune response. However, the immune response is temporary. As a result, patients may need to undergo repeated doses of passive immunotherapy treatments.
Who Is Eligible for Immunotherapy?
Some mesothelioma patients may be candidates for immunotherapy. The only FDA-approved immunotherapies for mesothelioma are checkpoint inhibitor drugs. Eligibility for checkpoint inhibitors depends on multiple factors.
In general, mesothelioma patients who do not qualify for surgery may be eligible. This means many patients may qualify for this form of immunotherapy.
Immunotherapy may be available through a prescribed treatment plan or clinical trials. Clinical trials each have unique eligibility criteria. Requirements can include the type of mesothelioma, cell type, stage and patient age. A patient’s doctor can help determine if the patient is eligible for specific clinical trials.
As cancer research progresses, more clinical trials may open for enrollment. Continuing research may improve the efficacy of immunotherapy, making it more widely available.
Resources for Mesothelioma Patients
05. Immunotherapy Types
Types of Immunotherapy
Many different immunotherapies are available, some of which already have FDA approval. Others are under investigation as treatments for different mesothelioma types and other cancers. Thus far, several types of immunotherapy have been studied for mesothelioma, including:
- Cancer vaccines
- CAR T cells
- Immune checkpoint inhibitors
- Monoclonal antibodies
- Oncolytic viruses
Each type of immunotherapy has possible side effects and benefits.
A cancer vaccine teaches the immune system to recognize a specific cancer as an intruder. This allows immune cells to attack cancer cells. Cancer vaccines are a form of active immunotherapy. As such, they may allow the body to continue fighting cancer long after vaccination.
Cancer vaccines have shown some promise in treating pleural mesothelioma patients. In one study, pleural mesothelioma patients underwent dendritic cell vaccination and chemotherapy. Seven patients in the study achieved survival of 24 months or longer. As of the last follow-up, two patients were still alive 50 months or more after .
CAR T-Cell Therapy
CAR T-cell therapy uses modified immune cells to fight cancer. Normal T cells, also known as white blood cells, protect the body from disease. But cancer cells know how to avoid detection and attack from normal T cells. CAR T-cell therapies fix this by reprogramming T cells to recognize and fight cancer.
Scientists use technology called a chimeric antigen receptor (CAR) to accomplish this. The CAR turns normal T cells into CAR T cells. It also teaches the T cells to identify and attack cancer cells.
A recent combination treatment used this technology to treat pleural mesothelioma. Patients had already undergone treatment. In the study, they received CAR T cells and Keytruda® (pembrolizumab). This treatment achieved a median survival of 23.9 months. This represents an improvement of more than a year compared to other second-line treatments.
As of 2022, the FDA has not approved CAR T-cell therapy for treating mesothelioma. This technology does have FDA approval to treat some other forms of cancer. CAR T-cell therapies are an active area of mesothelioma research.
What Is Adoptive Cell Therapy (ACT)?
Adoptive cell therapy is any form of immunotherapy in which a patient is treated with T cells. Some forms of ACT collect a patient’s own T cells, modify them, then give them back to the patient. CAR T-cell therapy is an example of this approach.
Other forms of ACT may treat patients with T cells that come from a donor. ACT may also be called adoptive cell transfer or cellular adoptive immunotherapy.
Immune Checkpoint Inhibitors
Immune checkpoint inhibitors are a type of monoclonal antibody. They allow the immune system to recognize and attack cancer cells. The FDA has approved the checkpoint inhibitor combination Opdivo + Yervoy for inoperable pleural mesothelioma.
Checkpoint inhibitors make it harder for cancer cells to fool the immune system at checkpoints. Immune checkpoints are safeguards that allow T cells to recognize and ignore healthy cells. But cancer cells can mimic healthy cells at these checkpoints. As a result, the immune system overlooks the cancer cells and does not attack.
Checkpoint inhibitors block these checkpoints so immune cells can fight cancer. These drugs can accomplish this by targeting specific checkpoints. In mesothelioma, these drugs target the PD-1/PD-L1 checkpoint and/or the CTLA-4 checkpoint.
Currently, the duo of Opdivo and Yervoy has FDA approval as a first-line treatment for some types of mesothelioma. In a clinical trial, Opdivo + Yervoy achieved a median survival of 18.1 months. Study patients also experienced improved quality of life with Opdivo + Yervoy versus chemotherapy. Other checkpoint inhibitors are the subject of ongoing clinical trials.
Monoclonal antibodies (mABs) are antibodies that help the immune system identify dangerous materials or cells in the body. In cancer treatment, mABs can be used to let immune cells identify and fight tumors.
So far, the FDA has approved a few monoclonal antibody treatments for cancer. Approved mAB treatments for mesothelioma include immune checkpoint inhibitors, a type of monoclonal antibody. As more clinical trials are completed, additional drugs may be approved.
Other Types of Immunotherapy
Researchers continue to test other types of immunotherapy. For example, they are testing immune system modulators which may enhance the immune system’s response to cancer. Some other types, like oncolytic viruses, have had promising results in early tests.
As research continues, other types of immunotherapies may come to the forefront of treatment options.
Oncolytic viruses are designed to infect and kill cancer cells without hurting healthy cells. Researchers tested an oncolytic virus called ONCOS-102 in a small trial. They treated patients who had mesothelioma, ovarian cancer and lung cancer. About 40% of patients saw their tumors stop growing in response to treatment. But these results were short-lived. Within six months, 100% of patients experienced continued growth of their cancer.
The short-term effect of this oncolytic virus may stem from shortcomings of this technology. Researchers have noted several weaknesses in oncolytic virus treatments, including:
- They may be discovered and inactivated by the immune system.
- They only reach the outer layers of tumor tissue.
Researchers continue to study oncolytic viruses. Their efforts may yet find a way to make these viruses an effective cancer treatment.
06. Future of Immunotherapy
The Future of Immunotherapy for Mesothelioma
Based on the success of checkpoint inhibitors, the future of immunotherapy seems bright. Continued research may help find even more safe, effective treatments.
Scientists are looking into immunotherapy combinations. Some may investigate cancer vaccines combined with checkpoint inhibitors. Others are testing immunotherapies in combination with surgery, chemotherapy or radiation.
Recent and Upcoming Clinical Trials
Immunotherapy and standard chemotherapy for pleural mesothelioma: Researchers are investigating the effectiveness of chemotherapy followed by a course of Imfinzi.
Immunotherapy with standard treatments for peritoneal mesothelioma: This study will investigate combining standard treatment with Tecentriq for peritoneal mesothelioma. This approach will be compared to standard treatment alone.
Cancer vaccine plus immune checkpoint inhibitors: This study focuses on using a cancer vaccine, galinpepimut-S, with a course of Opdivo. Results may help determine if the combination can help the immune system fight mesothelioma.
Opdivo + Yervoy for peritoneal mesothelioma: This phase II study will examine the effectiveness of Opdivo + Yervoy for peritoneal mesothelioma. This combination has FDA approval for some cases of pleural mesothelioma.
07. Common Questions
Common Questions About Mesothelioma Immunotherapy
Can immunotherapy be used for mesothelioma?
- Yes, some forms of immunotherapy are FDA-approved to treat different types of mesothelioma. For instance, Opdivo + Yervoy is approved for inoperable pleural mesothelioma. Patients interested in immunotherapy for mesothelioma should talk to their doctors about which options might be best suited for them.
What is the success rate of immunotherapy for mesothelioma?
- Determining the immunotherapy success rate for mesothelioma is difficult because many different types of immunotherapies and combinations are available. Finding the best immunotherapy for mesothelioma also depends on several factors. In a study, patients treated with Opdivo+Yervoy had better one- and two-year survival rates than patients treated with chemotherapy.
How long does immunotherapy work for mesothelioma?
- In some cases, immunotherapy treatments may have lasting effects after treatment ends. In studies, patients who had to discontinue treatment with Opdivo and Yervoy still saw benefits three years after discontinuing treatments.
Is immunotherapy better than chemotherapy?
Doctors may consider checkpoint inhibitors superior to chemotherapy in some cases. Checkpoint inhibitors generally cause more manageable side effects. In a pleural mesothelioma study, they improved survival and quality of life compared with chemotherapy.
This may not hold true for other immunotherapies. In such cases, chemotherapy may be right for some patients. People considering these therapies can discuss them with their doctors. An oncologist can help weigh the benefits and risks for each patient’s unique situation.