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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Written by Jenna Campagna, RN

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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:

1

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.

2

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.

3

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:

1

Immune cells don’t recognize cancerous cells as a threat, which allows them to replicate and spread.

2

Immunotherapy attaches to or kills cancerous cells, which alarms the immune system.

3

The patient’s immune cells recognize cancerous antigens and target cells with similar antigens.

4

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.

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

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

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

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:

1

Nivolumab (Opdivo), a PD‑1/PD‑L1 checkpoint inhibitor (FDA-approved)

2

Ipilimumab (Yervoy), a CTLA‑4/B7 checkpoint inhibitor (FDA‑approved)

3

Pembrolizumab (Keytruda), a PD‑1/PD‑L1 checkpoint inhibitor (limited FDA approval)

4

ONCOS‑102, an oncolytic virus (close to FDA approval)

5

Ramucirumab, monoclonal antibody

6

IcasM28z, an adoptive CAR T‑cell therapy

7

LMB‑100, a monoclonal antibody

8

Durvalumab (Imfinzi), a PD‑1/PD‑L1 checkpoint inhibitor

9

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:

  • Surgery
  • Chemotherapy
  • Radiation

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.

A report published in the Annals of Thoracic Surgery noted a very poor survival for these cases. All 75 cases in the study involved a mesothelioma surgery and PD‑L1 seemed to erase the progress of a resection.

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.

An example is the pairing of ramucirumab, a monoclonal antibody, with the chemotherapy drug gemcitabine. The combination led to median survival of 14 months — and a one‑year survival rate of 56% — compared to seven months for just chemotherapy.

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.

“As immunotherapy is coming more in favor, that may make radiation more in favor,” said Dr. Charles Simone, the chief medical officer of the New York Proton Center. “We have more evidence that immunotherapy and radiation together may have a synergistic effect.”

Common Questions About Immunotherapy for Mesothelioma

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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.

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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.

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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.

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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

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About the Writer, Jenna Campagna, RN

Jenna Campagna is a registered nurse and patient advocate who is passionate about helping mesothelioma patients navigate their health care. She has over seven years of experience working with patients diagnosed with rare diseases including mesothelioma. Jenna is also a member of the Academy of Oncology Nurse & Patient Navigators and her goal is to connect patients to top mesothelioma specialists, treatment facilities, and clinical trials. Through her writing, she aims to simplify the complicated journey through mesothelioma by offering helpful tips and advice.