Written By: Karen Selby, RN,
Last modified: September 21, 2021

What Is Mesothelioma Immunotherapy?

Immunotherapy is a new first-line treatment for mesothelioma. In October 2020, the U.S. Food and Drug Administration approved the Opdivo and Yervoy combination immunotherapy for malignant mesothelioma. Also known as nivolumab and ipilimumab respectively, these drugs are available for patients not eligible for surgery. 

Immunotherapy drugs for mesothelioma cancer, such as pembrolizumab (Keytruda), have extended the life expectancy of some patients by almost a year. Success rates for immunotherapy treatments vary for each patient.

Keytruda was the first FDA-approved immunotherapy for mesothelioma patients with advanced or metastatic disease. Mesothelioma specialists use Keytruda as second-line therapy for these patients, meaning after the initial treatment has failed.

Which Immunotherapies Work the Best Against Mesothelioma?

Several immunotherapy agents are now more widely available at specialized treatment centers. In addition, these medications have shown promising anti-cancer activity against mesothelioma in recent clinical trials. FDA-approved immunotherapies for malignant mesothelioma include:

  • Keytruda
  • Opdivo
  • Yervoy

Keytruda is effective against mesothelioma in some patients and helps them live longer when cancer recurs after first-line treatment. Speaking with The Mesothelioma Center, one mesothelioma survivor described a surgical treatment plan with Keytruda that saved his life. Another survivor reported that chemotherapy, Keytruda and surgery saved her life.

Opdivo and Yervoy combination immunotherapy is a beneficial option for patients newly diagnosed with mesothelioma who are not candidates for surgery. A 2017 French clinical trial reported that tumors shrank in 26% of participants treated with the Opdivo and Yervoy combination.

A 2021 clinical trial found that patients treated with Opdivo and Yervoy had a median overall survival of 18.1 months, compared with 14.1 months for chemotherapy patients. In addition, the two-year survival rate was 41% for patients treated with the immunotherapy combination, but only 27% for the chemotherapy group.

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Benefits of Immunotherapy

Immunotherapy is the hottest topic in cancer research and is widely considered the future of cancer treatment. Compared to chemotherapy or radiation, immunotherapy is a targeted therapy, which means it aims only to affect cancer cells and avoid damaging healthy tissue.

There are many types of immunotherapies, and researchers continue to uncover the best combinations and methods for treating all types of cancer. Aside from the ultimate advantage of potentially keeping cancer growth under control, the benefits of immunotherapy are numerous:

  • It harnesses the natural processes of your immune system to fight cancer internally.
  • Immunotherapy takes a targeted approach that kills only cancer cells, whereas chemotherapy also kills healthy cells.
  • Immunotherapy can create long-lasting protection against cancer for many years.
  • Some types of immunotherapies are specific to the cancer DNA of individual patients.
  • Immunotherapy available through clinical trials is paid for by the study sponsor.
  • The side effects of immunotherapy are fewer and often more manageable compared to other anticancer therapies.
Immunotherapy targeting cancer cells
Mesothelioma immunotherapy helping immune system kill cancer cells

Side Effects of Immunotherapy for Mesothelioma Patients

Most side effects of immunotherapy involve the body producing a heightened immune response, such as fevers or body aches when you’re fighting an infection. 

Most immunotherapy patients experience only mild or no side effects. Almost all side effects that do occur are reversible with medication or after treatment has ended. In rare cases, more severe reactions can damage sensitive tissue or organs over time. 

Typical immunotherapy side effects include:
  • Nausea
  • Diarrhea
  • Constipation
  • Fever
  • Weight loss
  • Fatigue
  • Diarrhea
  • Mouth sores
  • Skin irritation
  • Coughing
  • Muscle or joint pain

Serious side effects can occur when the immune system becomes hyperactive and antibodies accumulate in delicate organs such as the lungs or kidneys. Generally, these conditions are associated with inflammation, which can cause scarring or organ damage after long periods of time.

Severe immunotherapy adverse reactions include:
  • Pneumonia: Chest pain, shortness of breath and persistent cough
  • Colitis: Inflammation of the colon that causes bloody stools, abdominal pain and intestinal tearing
  • Hepatitis: Liver inflammation characterized by eye and skin discoloration, changes in urine and right-side abdominal pain
  • Hormone Gland Problems: Hormonal side effects include muscle aches, increased heart rate, headaches and weight loss
  • Kidney Problems: Nephritis, or inflammation of the kidneys, leads to changes in urine, back pain, hormone imbalance and potential kidney failure

Early treatment of immunotherapy side effects can help prevent long-term damage. In every patient’s case, it’s essential to discuss with a mesothelioma specialist the potential benefits versus risks of treatment.

Advantages and Disadvantages of Immunotherapy Treatments for Mesothelioma
Advantages:
  • Uses the immune system and the body’s cells to fight cancer
  • Targeted immunotherapy reduces damage to healthy tissues
  • When enrolled in a clinical trial, the research sponsor covers the cost of experimental immunotherapy
  • Side effects are fewer and more manageable than conventional mesothelioma treatment
Disadvantages:
  • Inflammation reactions such as skin irritation, pneumonitis or colitis
  • Potential organ damage such as scarring in the lungs or kidney issues
  • Fevers, nausea, diarrhea, body aches and other flu-like symptoms

How Does Immunotherapy Work?

A basic knowledge of the immune system helps people understand how immunotherapy works. The immune system has evolved to protect the body from foreign pathogens such as viruses and bacteria that cause disease. Immune cells also help remove other cells that are damaged or dead.

Dr. Jacques Fontaine video on malignant mesothelioma

Watch: Thoracic surgeon Dr. Jacques Fontaine describes how immunotherapy is one of the most innovative mesothelioma treatments available right now.

Your immune system recognizes internal and external causes of illness, including cancerous cells. At birth, your immune system carries the necessary information to protect you from many sicknesses. Your immune system develops as you grow, and it learns to recognize different types of disease. 

Active vs. Passive Immunity

Cancer immunotherapy drugs can be active or passive. Active immunotherapy creates a memory in the immune system that teaches immune cells how to recognize tumors. 

B cells are the immune agents responsible for producing antibodies that are the key to how your body “sees” diseases such as cancer. For example, even long after treatment with active immunotherapy, the body produces cancer-specific antibodies that identify tumor cells and mark them for destruction.

Examples of active immunotherapy:

  • Cancer Vaccines
  • CAR-T Cell Therapy

Passive immunotherapy has no lasting immunologic memory. Once you stop treatment, the effect goes away. Examples of passive immunotherapy include the monoclonal antibodies that characterize checkpoint inhibitors, such as Keytruda and Opdivo.

Examples of passive immunotherapy:

  • Immune Checkpoint Inhibitors
  • Cytokines

Researchers create monoclonal antibodies in a lab and then deliver those antibodies into the blood as medicine. In most cases, since your body did not make those antibodies, once they disappear the immune system doesn’t retain its memory of when they were present and no longer attacks tumors.

Types of Immunotherapy for Mesothelioma

Clinical trials have studied different types of immunotherapy for mesothelioma since the 1970s. However, recent breakthroughs in research, such as Keytruda and other immune checkpoint inhibitors, made immunotherapy a more viable treatment option for mesothelioma.

Immune Checkpoint Inhibitors

Immune checkpoint inhibitors are drugs that stop cancer cells from hiding in the body as healthy cells. Checkpoint inhibitors remove the checkpoints or blockades that cancer uses to disguise itself, allowing the immune system to recognize them as cancer and attack. Checkpoint inhibitors for mesothelioma target checkpoints such as CTLA-4PD-1 and PD-L1.

The most promising checkpoint inhibitors for mesothelioma include Keytruda, Opdivo, Yervoy and Imfinzi (Durvalumab). Another checkpoint inhibitor called SS1P helped control tumors in mesothelioma patients, but not enough to warrant further study.

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Cancer Vaccines

Research is underway in Hawaii to develop a preventative mesothelioma vaccine. Cancer vaccines work like vaccines for the flu and other illnesses by helping prevent specific diseases from coming back.

Quick Fact:
There are two types of cancer vaccines: Preventive and therapeutic. Preventive vaccines decrease the chance of recurrent illness, and therapeutic vaccines attempt to treat active disease.

Clinical trials have studied therapeutic vaccines for mesothelioma. Two in particular, the listeria-based cancer vaccine CRS-207 and galinpepimut-S (WT1), have shown the most promise. A phase II clinical trial of the WT1 vaccine reported significantly longer survival and better tumor control among participants who received the vaccine versus the placebo.

Monoclonal Antibodies

Monoclonal antibody therapy (mAb) is the most used cancer immunotherapy, but it’s not necessarily the most common immunotherapy for mesothelioma. Antibody therapy, like all immunotherapy, is a targeted treatment focusing on a single site, called an antigen, within cancer cells or on their surface. 

Tremelimumab is both a monoclonal antibody and an immune checkpoint inhibitor under investigation for mesothelioma. Amatuximab (MORAb-009) is a monoclonal antibody that made it to a phase II clinical trial for mesothelioma patients. Overall survival was 14.8 months, almost 25% longer than the average survival for mesothelioma patients.

One mesothelioma patient, Andy A., responded abnormally well to amatuximab during a clinical trial. As a result, Andy was allowed to stay on the drug for years after the study technically ended because it continued to keep his mesothelioma in control. However, when the drug suddenly stopped working, Andy turned to complementary therapies and cannabis oil.

Other Immunotherapies

Other types of immunotherapies for mesothelioma include adoptive cell transfer and cytokines. These treatments use different ways of producing an immune response so the body can identify and attack cancer cells.  

Adoptive Cell Transfer

Transferring live, whole immune cells into patients is a practice researchers use on those with advanced metastatic melanoma or renal cell carcinoma. Researchers are also investigating adoptive cell transfer for use in patients with mesothelioma.

Injection of dendritic cells following chemotherapy has been tested in phase I clinical trials. Ten patients previously treated with cisplatin and pemetrexed tolerated the therapy well, and the study’s participants showed strong immune responses. 

Another type of adoptive cell transfer undergoing mesothelioma clinical trials is CAR T-cell therapy. This therapy modifies patients’ immune cells, called T cells, to make them cancer-specific. T cells help B cells make antibodies and raise an immune response after identifying an antigen, a marker on the surface of diseased cells and foreign pathogens such as viruses.

Cytokines

Cytokines are proteins made by T cells that coordinate immune responses against cancer and foreign pathogens. Cytokines such as tumor necrosis factor, interferon and interleukin-2 are used in immunotherapy to kill cancer cells or stop the birth of new cells. 

These proteins interact directly with the tumor cells and either work independently or as a coordinated attack to produce a more robust immune reaction.

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Future of Immunotherapy for Mesothelioma

Immunotherapy will likely become an effective treatment option for mesothelioma in the future, especially when combined with other cancer therapies. For example, some studies have paired immunotherapy with chemotherapy or surgery, and recent results show significant survival benefits for certain patients.

I believe immunotherapy will become the fourth pillar of treatment for mesothelioma [joining surgery, radiation and chemotherapy]. It could help turn mesothelioma into a chronic disease that people can live with for a long time.
Dr. Dan Sterman
Director of pulmonary medicine at New York University

Researchers have discovered a direct correlation between tumor-infiltrating lymphocytes, which are white blood cells that can penetrate tumors, and mesothelioma prognosis. These results indicate that an enhanced immune response may improve patient outcomes. 

Studies suggest that asbestos, the mineral that causes mesothelioma, compromises immune cells, contributing to its ability to cause cancer. In the future, preventive cancer vaccines for people exposed to asbestos could significantly decrease mesothelioma cancer risk.

Mesothelioma specialists offer immunotherapy to patients as a standard-of-care therapy, matching clinical trials or compassionate use programs. The recent FDA approval of Keytruda, Opdivo and Yervoy to treat mesothelioma represents the first steps in the broader availability of immunotherapy options.

Common Questions About Immunotherapy for Mesothelioma

Can immunotherapy be used to treat mesothelioma?

Immunotherapy is an experimental mesothelioma treatment option. Clinical research trials are currently ongoing to test the safety and effectiveness of this new therapy. Immunotherapy boosts a patient’s immune system to help treat cancer and works in conjunction with chemotherapy, surgery and other treatments.

What is the success rate of immunotherapy?

Immunotherapy success varies for each patient based on type and stage of cancer as well as the patient’s immune system. Pembrolizumab (Keytruda) is one of the most promising immunotherapy options for malignant pleural mesothelioma. In many cases, Keytruda has extended the life expectancy of patients by almost a year.

What are the disadvantages of immunotherapy?

Immunotherapy results vary because treatment is predominantly dependent on the activity of the patient’s immune system and the presence of biomarkers on the tumor’s surface. Mesothelioma symptoms and treatment side effects may also be more severe in some patients based on the intensity of the immune reaction.

Is immunotherapy better than chemotherapy?

There are advantages and disadvantages to each treatment. Some patients might find they have fewer side effects with immunotherapy, while chemotherapy for mesothelioma may better control their tumor growth. Many oncologists use a combination approach that employs both therapies for optimal impact.


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