01. What Is Immunotherapy?
What Is Immunotherapy?
Immunotherapy treatments use a patient’s immune system to fight diseases, such as cancer. As a cancer treatment, immunotherapy may be used in conjunction with other treatments, including surgery or chemotherapy.
As an emerging cancer treatment, immunotherapy research is ongoing. However, the Food and Drug Administration (FDA) has approved some immunotherapy drugs for certain cancers, including mesothelioma. FDA approval means the treatments could become more widely available outside of clinical trials.
In October 2020, the FDA approved the combination immunotherapy of Opdivo®️ and Yervoy®️ as a first-line treatment for unresectable malignant pleural mesothelioma. This was the first FDA approval for a drug regimen for mesothelioma treatment in 16 years.
How Does Immunotherapy Work?
Immunotherapy for cancer uses certain aspects of the immune system to fight and kill cancer cells. The basic functions of the immune system are to recognize, kill and remove intruders in the body.
Sometimes, the immune system fails to recognize cancer cells in the body or doesn’t have a strong enough response to kill the cells. With cancer immunotherapy, doctors use natural or modified components of the immune system to help recognize and fight the cancer cells.
|Important Immune System Components for Immunotherapy|
|Antibody||A protein component that recognizes foreign material and alerts the rest of the immune system.|
|Antigen||Proteins capable of triggering antibody production.|
|Immune Checkpoint||A point within the immune response that prevents immune cells from attacking healthy, native cells.|
|Natural Killer Cells||Immune cells that can kill virus-infected cells and early-stage cancer cells.|
|T Cell||White blood cells that can kill infected cells and recruit and stimulate other immune cells.|
Immunotherapy treatment can be broken up into two broad categories: passive and active. Doctors base the categories on how the treatment affects the immune system over time.
- Passive Immunotherapy: Passive immunotherapy introduces synthetic immune proteins into a patient’s body to help fight cancer. The synthetic proteins trigger an immune response. However, the immune response is temporary. As a result, patients may need to undergo repeated doses of passive immunotherapy treatments.
- Active Immunotherapy: Active immunotherapy evokes a lasting response within the immune system through use of immune memory. It works by stimulating the immune system to act against the cancer cells.
Immunotherapy treatments can be passive, active or a combination of the two.
02. Types of Immunotherapy
Types of Immunotherapy for Mesothelioma
There are many types of immunotherapy used to treat mesothelioma and other cancers. For mesothelioma, researchers have focused on a few types of immunotherapy, including:
- Adoptive cell therapy (also called adoptive cell transfer or ACT)
- Cancer vaccines
- Monoclonal antibodies
- Immune checkpoint inhibitors
- Oncolytic viruses
Each type of immunotherapy has possible side effects and benefits.
Adoptive Cell Therapy (ACT)
Adoptive cell therapy treats cancer by enhancing a patient’s T cells. T cells are white blood cells that help trigger an immune response and can attack cancer cells. Sometimes called adoptive cell transfer, ACT is a passive form of immunotherapy.
There are several types of ACT. In general, this form of immunotherapy involves transferring healthy T cells to a patient. The transferred T cells may have been removed from the patient and replicated in a lab. In other cases, the T cells are donated from another individual. The process to grow large amounts of T cells takes 2 – 8 weeks to complete.
Once replicated, the T cells are reintroduced to the patient via injection. The lab-grown T cells will then help the immune system fight cancer.
What Is CAR T-Cell Therapy?
CAR T-cell therapy is a type of ACT. CAR T-cell therapy has shown early promising results in malignant pleural mesothelioma patients. This kind of ACT uses special T cells called chimeric antigen receptor (CAR) T-cells to recognize and kill cancer cells. Ongoing clinical trials are investigating the efficacy of CAR T-cell therapy for mesothelioma cancer patients.
Cancer vaccines are different from traditional vaccines against viruses. This type of immunotherapy teaches the patient’s immune system how to recognize a specific cancer as an intruder. This allows the immune system to attack the cancer cells.
Cancer vaccines are a form of active immunotherapy. As a result, this therapy may result in lasting cell memory that allows the body to continue to attack the cancer long after vaccination.
Cancer vaccines have shown promise in treating pleural mesothelioma patients. In one clinical trial, doctors treated patients with a dendritic cell vaccination and chemotherapy. Seven patients in the study achieved survival of 24 months or longer. As of the last follow-up, researchers noted two patients survived for 50 and 66 months.
Monoclonal antibodies (mAbs) are antibodies targeting a specific protein to help the immune system recognize and/or attack cancer cells. They are lab-produced proteins engineered to attach to specific antigens found on cancer cells. This makes it easier for the immune system to identify the cancer cells and trigger a response.
Monoclonal antibodies are an example of passive immunotherapy.
So far, the FDA has approved a couple of monoclonal antibody treatments for cancer. Approved monoclonal antibodies include ramucirumab (Cyramza®️) and bevacizumab (Avastin®️). So far, the FDA has not approved either for mesothelioma. However, the drugs have shown promising results in clinical trials.
Bevacizumab + Chemotherapy May Extend Mesothelioma Survival
Researchers tested bevacizumab combined with two chemotherapy drugs (cisplatin and pemetrexed) for pleural mesothelioma. They found an overall median survival of 18.8 months for 223 patients treated with the combination therapy. Patients in the trial treated with chemotherapy alone had a median overall survival of 16.1 months. On average, pleural mesothelioma patient life expectancy is 6 – 12 months after diagnosis.
The National Comprehensive Cancer Network (NCCN) added a combination of pemetrexed, cisplatin and bevacizumab as a recommended first-line treatment for mesothelioma patients who cannot undergo surgery.
Immune Checkpoint Inhibitors
Immune checkpoint inhibitors are a type of monoclonal antibody. They make it difficult for cancer cells to hide from the immune system.
Cancer cells often mimic healthy cells. As a result, the immune system overlooks the cancer cells and doesn’t attack. Checkpoint inhibitors make it harder for cancer cells to appear healthy by targeting specific proteins, such as PD-L1 or CTLA-4. This allows the immune system to recognize the cancer cells and kill them.
The two most well-known PD-1 checkpoint inhibitors for mesothelioma are Keytruda® and Opdivo®️.
Immune checkpoint inhibitors are currently FDA approved for the treatment of bladder cancer, non-small cell and small cell lung cancers, and melanoma. Studies have shown similarities between melanoma and mesothelioma in the past. As a result, researchers are investigating using checkpoint inhibitors for mesothelioma cancer treatment.
Oncolytic viruses are capable of infecting and killing cancer cells without damaging normal, healthy cells. As a result, they may make first-line treatments, such as chemotherapy, more effective against cancer.
Specialists modify these viruses in a laboratory to kill cancer cells. Oncolytic viruses are a potential second-line treatment for patients who have not had success with other immunotherapy treatments.
In one study, researchers tested an oncolytic virus on patients with various types of cancer, including mesothelioma, ovarian cancer and lung cancer. The oncolytic virus (ONCOS-102) stimulated the immune system to invade and attack solid tumors. Researchers consider this a promising result, as immune cells do not often migrate inside of solid tumors. Research into ONCOS-102 and other oncolytic viruses is ongoing.
Resources for Mesothelioma Patients
03. How Immunotherapy Treats Mesothelioma
How Does Immunotherapy Treat Mesothelioma?
Immunotherapy treatments work by enhancing the immune system response to mesothelioma cancer cells. However, it is not used to cure the cancer. Mesothelioma has no cure, but therapeutic options like immunotherapy may help patients extend life expectancy.
Mesothelioma immunotherapy treatments may have a few main goals, including:
- To reduce the possibility of cancer recurrence
- To maximize the efficacy of first-line treatments, such as chemotherapy and radiation
- To extend patient life expectancy after first-line treatments
Researchers continue to test immunotherapy treatments for mesothelioma and other cancers. As medical research for immunotherapy continues, the success and limitations of the treatment could become more clear.
Who Is Eligible for Immunotherapy?
Many mesothelioma patients may be candidates for immunotherapy. Only a mesothelioma specialist can determine which patients are best suited to immunotherapy. Some patients with pre-existing immune conditions may not be eligible for 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. Patients should discuss potential benefits and risks of immunotherapy with their medical team before enrolling in a trial.
As cancer research progresses, more clinical trials will likely become available. Continuing research may improve the efficacy of the treatment, allowing it to be widely available to more patients.
04. How Successful Is Mesothelioma Immunotherapy?
How Successful Is Immunotherapy for Mesothelioma?
Various clinical trials have found success in treating some mesothelioma patients with immunotherapy. The efficacy of immunotherapy varies based on the type of treatment, cancer progression and previous treatment methods.
Researchers have seen promising results treating mesothelioma with Keytruda® or Opdivo® in combination with Yervoy®.
In some studies, researchers have also found the following immunotherapy drugs extended life expectancy for some mesothelioma patients:
- Avastin®️ (bevacizumab): In one study, researchers found a median survival of 18.8 months for mesothelioma patients treated with a combination of chemotherapy drugs and bevacizumab.
- CAR T-cell therapy: In an ongoing clinical trial, researchers are testing an intrapleural infusion of CAR T-cells. So far, researchers found tumor reduction in about 50% of pleural mesothelioma patients who underwent this treatment.
Currently, only Opdivo®️ in combination with Yervoy®️ is FDA approved as a first-line treatment for mesothelioma patients. However, other modes of immunotherapy are recommended for second-line treatment.
Researchers continue to study and research additional immunotherapies in clinical trials.
Keytruda® is an immune checkpoint inhibitor that is effective against mesothelioma in some patients. It functions by blocking the PD-L1 protein, which exists on normal and cancerous cells. The protein can trick the immune system into thinking cancer cells are healthy cells. As a result, the immune system doesn’t attack the cancer cells.
By blocking this PD-L1 protein, Keytruda® allows the immune system to attack cancer cells.
In clinical trials, Keytruda® has successfully extended patient life expectancy and contributed to tumor size reduction. In a prominent clinical trial dubbed KEYNOTE-028, researchers found an average survival of 18 months for mesothelioma patients treated with Keytruda®.
Keytruda® is not yet FDA approved for mesothelioma. However, the National Comprehensive Cancer Network (NCCN) recommends it as a subsequent treatment option for pleural mesothelioma patients who have already received chemotherapy.
Opdivo®️ (nivolumab) and Yervoy®️ (ipilimumab)
The first-line treatment combination of Opdivo®️ and Yervoy®️ is the first FDA-approved treatment for malignant pleural mesothelioma patients in 16 years. These drugs are monoclonal antibodies functioning as immune checkpoint inhibitors.
This treatment is especially promising for patients unable to undergo surgery.
In one clinical trial, researchers treated 605 patients with unresectable pleural mesothelioma with Opdivo® and Yervoy®. They found the combination immunotherapy treatment increased median survival compared to patients treated solely with chemotherapy. Patients in this study had a median survival of 18.1 months when treated with Yervoy®️ and Opdivo®️. Those treated with just chemotherapy had a median survival of 14.1 months.
05. What Can Patients Expect From Immunotherapy?
What Can Patients Expect From Immunotherapy Treatment?
The success and side effects of immunotherapy vary on a case-by-case basis. Some variables include patient age, cancer progression and cancer stage at diagnosis. Side effects also differ depending on the specific immunotherapy drug.
Common side effects of immunotherapy treatments include:
- Body aches
- Loss of appetite
- Rash or itching
Common side effects related to immunotherapy are mild. However, there are rare instances of more serious issues. More severe side effects may include problems within the organs such as the lungs, intestines or liver.
In addition to potential side effects, researchers have also noted other potential drawbacks and benefits.
Benefits and Drawbacks of Immunotherapy for Mesothelioma
Immunotherapy uses natural immune functions to fight cancer. This may lead to fewer side effects during treatment. Immunotherapy is also targeted at killing cancer cells, leaving most healthy cells intact. With systemic treatments, like traditional chemotherapy, healthy cells can face damage and lead to side effects.
Immunotherapies trigger immune responses to fight cancer, so patients may experience flu-like symptoms or other signs of a very active immune system. Additionally, while active immunotherapy treatments have prolonged effects, patients may need to undergo multiple treatments with passive immunotherapies.
Is Immunotherapy Painful?
Immunotherapy side effects can be mild, moderate or severe depending on an individual’s unique case. In some trials, patients report few to no side effects.
Pain associated with immunotherapy treatment varies from patient to patient. For patients who do experience pain or other side effects, doctors may recommend palliative care options. Palliative treatments can help manage symptoms and improve patient quality of life. Doctors will help patients assess how to move forward if side effects are unacceptable.
Is Immunotherapy Better Than Chemotherapy?
Every patient’s case is unique and success rates for treatments vary. As such, it is difficult for doctors to definitively say if immunotherapy is better than chemotherapy. There are benefits and drawbacks for each kind of treatment.
Chemotherapy treatments have long been a standard cancer treatment. For instance, the FDA approved cisplatin or carboplatin with pemetrexed for mesothelioma treatment in 2004. Immunotherapy is still a new treatment undergoing trials for mesothelioma and other cancers. As such, researchers are still learning about its efficacy and potential drawbacks.
Standard chemotherapy is often administered systemically and targets fast-growing cells. As a result, chemotherapy drugs do not distinguish between healthy and cancerous cells. Patients undergoing chemotherapy often experience a wide range of uncomfortable side effects.
Immunotherapy is a targeted treatment that often results in fewer side effects. However, researchers continue to study the success and potential side effects of immunotherapy.
Mesothelioma patients should discuss potential risks and benefits of treatment options with their doctor.