Important Facts About Immunotherapy for Mesothelioma

The FDA in 2020 approved Opdivo and Yervoy for mesothelioma. The drugs must be used together and only for cases where surgery isnt 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.

For patients interested in how to get mesothelioma immunotherapy treatment, here are three steps to receive this promising option:

Heres 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 whats normal and whats 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 advocatefor help finding a cancer center. If you dont already have a mesothelioma specialist, reach out to our team. We can direct you to nearby cancer centers offering immunotherapy treatment.

Your immune system has various components. Each plays a role in detecting and responding to mesothelioma and other cancers:

The presence of antigens raises the immune systems alarm. The primary tumor antigen for mesothelioma is a protein called mesothelin.

Mesothelin is the signal for Bcells to produce antibodies. Once they attach to mesothelin, Tcells should identify and kill the labeled diseased cells.

Immunotherapy can signal to Bcells to produce more antibodies or enhance Tcells against mesothelioma.

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.

Heres how some immunotherapy drugs fight cancers like mesothelioma:

1

Immune cells dont 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 patients immune cells recognize cancerous antigens and target cells with similar antigens.

4

The patients immune cells seek out the remaining cancer cells, leaving healthy cells unharmed.

Other immunotherapy drugs add labaltered Tcells or labproduced antibodies to aid the immune system.

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.

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 block mesothelioma cells from subduing the immune system Tcells. 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 Tcells proteins. The most familiar to doctors and researchers are PDL1 and PD1.

PDL1, the acronym for programmed deathligand 1, is a surface protein on mesothelioma cells. PD1, the acronym for programmed cell death protein 1, is a surface protein receptor on Tcells.

When PD1 binds with PDL1, the Tcells ignore mesothelioma cells. PD1/PDL1 checkpoint inhibitors act as a wall between the protein and receptor. The drugs prevent, or break, the binding and allow Tcells to defend the body.

Examples of PD1/PDL1 checkpoint inhibitors include:

Another example is a CTLA4/B7 checkpoint inhibitor. These drugs block CTLA4 (immune cell receptor) and B7 (mesothelioma cell protein).

The main example is Yervoy, the brand name for ipilimumab.

Oncolytic viruses deliver an antigen into the body to elicit an immune reaction. This is a combination of virotherapy and immunotherapy, and its another form of active immunotherapy.

Oncolytic viruses work like regular viruses except they dont attack healthy cells. They kill only diseased cells, which release antigens that cause an immune response.

An example is mesothelioma oncolytic virus ONCOS102. The therapy breaks up mesothelioma cells, which releases antigens. The virus then requests for the Tcells to swarm to the site of the cancer.

Adoptive cell therapy alters immune system cells in a laboratory to better fight cancers like mesothelioma. Usually immunotherapy experts will alter Tcells, which are the soldiers protecting the body from diseases.

The most familiar adoptive cell therapy for mesothelioma is CAR Tcell therapy. CAR is an acronym for chimeric antigen receptor. This form of immunotherapy uses labcreated receptors to target mesothelioma specifically.

IcasM28z is an example of adoptive cell therapy. The CAR Tcells target mesothelin, a protein found on the surface of mesothelioma cells.

Monoclonal antibodies are labgenerated antibodies inserted into the body to fight mesothelioma. Its 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 LMB100, ramucirumab and anetumab ravtansine.

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 PD1/PDL1 checkpoint inhibitor (FDA-approved)

2

Ipilimumab (Yervoy), a CTLA4/B7 checkpoint inhibitor (FDAapproved)

3

Pembrolizumab (Keytruda), a PD1/PDL1 checkpoint inhibitor (limited FDA approval)

4

ONCOS102, an oncolytic virus (close to FDA approval)

5

Ramucirumab, monoclonal antibody

6

IcasM28z, an adoptive CAR Tcell therapy

7

LMB100, a monoclonal antibody

8

Durvalumab (Imfinzi), a PD1/PDL1 checkpoint inhibitor

9

Anetumab ravtansine, a monoclonal antibody

Each is either FDAapproved or part of mesothelioma clinical trials.

FDAapproved mesothelioma immunotherapy options range in median survival from 1820 months. Survival variables include the type of immunotherapy, the patients 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:

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:

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 PDL1 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 PDL1 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.

Doctors often pair investigative immunotherapy drugs with mesothelioma chemotherapy in clinical studies. The combination of cancerkilling drugs with immuneenhancing 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 oneyear survival rate of 56% compared to seven months for just chemotherapy.

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 Tcells prepared to fight.

Radiation also can partially kill tumors, clumps of diseased cells, which then release antigens. These antigens are what the Tcells look for, and immunotherapy can amplify the immune systems 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.

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 diseases progress and extends the patients life. Numerous studies report survival times of multiple years thanks to immunotherapy.

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.

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 PDL1 tumor burden. PDL1 is a cancerous protein that links with PD1, an immune system receptor, and inhibits the immune system response. Keytruda blocks the connection.

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 dont meet the FDAs criteria can enroll in clinical trials to receive immunotherapy on an experimental basis.

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.

Last Edited: July 6, 2021.

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Immunotherapy for Mesothelioma: Types, Drug Options and Survival Rates - Mesothelioma Guide