What Is Mesothelioma Immunotherapy?

Mesothelioma immunotherapy is a targeted anti-cancer treatment that utilizes or modifies cells from a patient’s immune system.

In 2020, the U.S. Food and Drug Administration approved Opdivo and Yervoy combination immunotherapy treatment for mesothelioma. These drugs, known generically as nivolumab and ipilimumab, aid the immune system in recognizing cancer cells and stimulate the production of T cells.

Diagram of how immunotherapy drugs treat mesothelioma
Immune cells locate and destroy mesothelioma cancer cells.

Immunotherapy for mesothelioma cancer, such as pembrolizumab, has extended the life expectancy of some patients by almost a year. This drug, known by the brand name Keytruda, was the first FDA-approved immunotherapy for mesothelioma patients with advanced or metastatic disease. Success rates for immunotherapy treatments vary for each patient.

How Does Mesothelioma Immunotherapy Work?

Mesothelioma immunotherapy works by modifying and improving the immune system’s ability to recognize and eliminate cancer cells. This process is similar to how the body fights foreign pathogens such as viruses and bacteria that cause disease. Immune cells also help remove other cells that are damaged or dead.

Active vs. Passive Immunity

Active immunity occurs when the body creates antibodies, and passive immunity involves artificial immune cells that provide protection. After treatment with active immunotherapies, such as cancer vaccines or CAR T-cell therapy, the immune system remembers how to produce anti-cancer antibodies to decrease the cancer recurrence rate.

Passive immunotherapy, such as immune checkpoint inhibitors or cytokines, has no lasting immunologic memory. Once you stop treatment, the anti-cancer effects of the immune system fade over time. Unlike active immunity, these treatments do not stimulate the body to create long-lasting antibodies.

Patients and caregivers should weigh the benefits and risks of active or passive immunotherapy options. For example, cancer vaccines are most effective at preventing cancer from returning after success with other treatments. Immune checkpoint inhibitors are very effective for some mesothelioma patients but can cause severe side effects.

Types of Immunotherapy for Mesothelioma

There are several types of immunotherapy for mesothelioma, including immune checkpoint inhibitors, cancer vaccines, monoclonal antibodies and CAR T-cell therapy. Immunotherapy availability varies based on cancer stage and the patient’s previous treatment history.

Clinical trials continue to examine the safety and effectiveness of new types of mesothelioma immunotherapy. In recent years, thanks to FDA approval, Keytruda and other immune checkpoint inhibitors have made immunotherapy a viable treatment option for mesothelioma.

Cancer Vaccines

Cancer vaccines work like vaccines for the flu and other illnesses by helping prevent specific diseases from coming back. There are two types of cancer vaccines: Preventative and therapeutic. Preventative vaccines decrease the chance of recurrent cancer, and therapeutic vaccines attempt to treat active disease.

One preventative mesothelioma vaccine that targets the OX40 receptor has led to decreased tumor growth and increased survival in mice carrying mesothelioma tumors. Researchers are studying whether this vaccine could be safe in humans and effectively prevent mesothelioma recurrence.

Two therapeutic vaccines for mesothelioma, the listeria-based cancer vaccine CRS-207 and galinpepimut-S (WT1), have shown promise in clinical trials. A phase II 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 common immunotherapy for many cancers but not necessarily for mesothelioma. Antibody therapy is a targeted treatment focusing on a single site, called an antigen, within cancer cells or on their surface. The treatment involves making many copies of the effective antibody in a lab and transfusing them to patients.

Tremelimumab is both a monoclonal antibody and an immune checkpoint inhibitor under investigation for mesothelioma. Amatuximab (MORAb-009) is a monoclonal antibody that has progressed 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.

Cell and Protein Therapies

Adoptive cell transfer involves transferring whole immune cells into patients and is under study for use in patients with mesothelioma. This therapy has been successful for advanced melanoma and renal cell carcinoma. Another type of adoptive cell transfer, CAR T-cell therapy, modifies immune system T cells to make them cancer-specific.

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

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 work independently or as a coordinated attack to kill cancer cells or stop the birth of new cells.

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What Are the Best Immunotherapy Treatments for Mesothelioma?

The best immunotherapy medications for mesothelioma, such as Opdivo and Yervoy, have shown promising anti-cancer activity in recent clinical trials. Newer experimental treatments include immune checkpoint inhibitors for peritoneal mesothelioma and targeted therapies, such as the WT1 vaccine. 

FDA-approved immunotherapies for malignant mesothelioma include:
  • Keytruda
  • Opdivo
  • Yervoy

Keytruda is effective against mesothelioma when cancer recurs after first-line treatment. It has led to an average overall patient survival of 18 months. Opdivo and Yervoy combination immunotherapy is a beneficial option for patients newly diagnosed with pleural mesothelioma who are not candidates for surgery.

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.

Benefits of Immunotherapy for Mesothelioma

The primary benefit of immunotherapy for mesothelioma is that it is a targeted treatment and aims only to affect cancer cells and avoid damaging healthy tissue, unlike chemotherapy or radiation. The side effects of immunotherapy are fewer and often more manageable compared to other anti-cancer treatments.

Immunotherapy and other targeted therapies are widely considered the future of cancer treatment for mesothelioma patients. By taking advantage of the natural processes of your immune system, immunotherapy can create long-lasting protection against mesothelioma for many years.

Advantages And Disadvantages Of Immunotherapy Treatments For Mesothelioma
  • 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
  • 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

Other benefits of immunotherapy for mesothelioma include personalized treatment and financial support. Some types of immunotherapies are specific to the cancer DNA of individual patients, and immunotherapy available through clinical trials is paid for by the study sponsor.

Side Effects of Immunotherapy for Mesothelioma Patients

Side effects of immunotherapy for mesothelioma patients involve reactions resulting from a heightened immune response, such as fevers or body aches, like fighting an infection. Some side effects, such as coughing or fatigue, can be more uncomfortable for mesothelioma patients experiencing shortness of breath due to cancer.

Most mesothelioma patients experience only mild side effects with immunotherapy, and doctors monitor whether there is a need to slow or stop treatment. Almost all immunotherapy side effects are reversible with rest or medication. In rare cases, more severe reactions can damage sensitive tissue or organs.

Typical Immunotherapy Side Effects Include:
  • Nausea
  • Diarrhea
  • Constipation
  • Fever
  • Weight loss
  • Fatigue
  • Mouth sores
  • Skin irritation
  • Coughing
  • Muscle or joint pain

Serious side effects can occur when the immune system overproduces antibodies that 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. Lifestyle changes and habits, such as a mesothelioma diet, can improve energy and reduce the severity of some side effects. 

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Cost of Immunotherapy

The cost of immunotherapy for mesothelioma patients can be prohibitively expensive for many people, often costing over $10,000 per month. According to a recent Reuters report, Yervoy and Opdivo combination therapy can cost more than $250,000 annually. Other immune checkpoint inhibitors can cost roughly $150,000 per year.

Medicare and many insurance plans cover cancer immunotherapy, but out-of-pocket expenses and lost wages can significantly impact personal finances. VA benefits cover immunotherapy with limited to no out-of-pocket fees, but the veterans claims system can be complicated.

Patient Advocates can help patients and their families identify financial assistance opportunities for medical care, such as clinical trials or legal compensation. The Veterans Outreach team at The Mesothelioma Center can also help patients file VA claims.

Future of Immunotherapy for Mesothelioma

Immunotherapy for mesothelioma in the future will likely involve a combination 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.

Future immunotherapy options for mesothelioma could include tumor-infiltrating lymphocytes, a type of white blood cell that invades tumors. This therapy signals a broader immune response alongside other treatments and may improve mesothelioma prognosis. Advanced preventative vaccines could disrupt the ability of asbestos to cause cancer, reducing risk after exposure.

Mesothelioma specialists provide access to the latest experimental immunotherapies through 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 the type and stage of cancer and 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.

Is immunotherapy equally effective for men and women?

A systematic review and meta-analysis of 20 studies published in 2018 in Lancet Oncology included 11,351 people with various types of metastatic cancer. Researchers reported men receiving checkpoint inhibitors had a 28% reduced risk of dying during the study period vs a 14% reduced risk for women.

However, a July 2020 report in Biomedicines found that there was an overall survival benefit of immunotherapy for both men and women. No statistically significant difference between men and women’s responses to immunotherapy were found.

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 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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