Immune Checkpoint Inhibitors for Mesothelioma

Immune checkpoint inhibitors are a class of immunotherapy drugs that help the immune system fight cancer. Clinical trials are currently testing these drugs on mesothelioma.

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This page features: 11 cited research articles

Immune checkpoint inhibitors target specific proteins on the surface of cancer cells called antigens. In turn, the inhibitory effects of tumor cells on immune cells are minimized. This allows the immune system to better control the cancer

Clinical trials are testing these innovative drugs to discover if they could play a role in the treatment of mesothelioma.

Immune checkpoint inhibitors that have or are being been tested on mesothelioma include:

None of these immunotherapy drugs have been approved to treat mesothelioma by the U.S. Food and Drug Administration (FDA), but several ongoing clinical trials could lead to approval.

The FDA has approved several immune checkpoint inhibitors to treat other cancers.

  • Yervoy was approved in 2011 to treat melanoma.

  • Keytruda was approved in 2014 to treat melanoma and was later approved to treat lung cancer, head and neck cancer, Hodgkin lymphoma, bladder cancer, gastric cancer and solid tumors with certain biomarkers.

  • Opdivo was approved in 2014 to treat melanoma and was later approved to treat lung cancer, kidney cancer, Hodgkin lymphoma, head and neck cancer, bladder cancer, colorectal cancer and liver cancer.

  • Atezolizumab (Tecentriq) was approved in 2016 to treat bladder cancer and was later approved to treat lung cancer.

  • Avelumab (Bavencio) was approved in 2017 to treat Merkel cell carcinoma and bladder cancer.

  • Imfinzi was approved in 2017 to treat bladder cancer.

Research on mesothelioma has shown that several immune checkpoint inhibitors are effective against the asbestos-related cancer, especially Keytruda and the combination of Opdivo and Yervoy.

How Do Immune Checkpoint Inhibitors Work?

Checkpoint inhibitors are antibodies that block antigens on the surface of cancer cells or block proteins on immune cells called T cells. Antigens work like a mask to hide cancer cells from the immune system.

These antigens are also called immune checkpoints.

Drugs that inhibit checkpoint antigens effectively unmask cancer cells, allowing the immune system to recognize and attack the cancer.

The antigens that checkpoint inhibitors block include CTLA-4 and PD-L1.

  • Imfinzi targets PD-L1.

  • Yervoy and tremelimumab target CTLA-4.

Keytruda and Opdivo target PD-1, a checkpoint protein on the surface of T cells. PD-1 normally attaches to PD-L1. By preventing this interaction, T cells are not fooled into thinking cancerous cells are healthy, allowing for an immune response.

Out of all of these drugs, Keytruda is the most well-known. In 2015, former U.S. President Jimmy Carter said Keytruda put his malignant melanoma into remission.

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Side Effects of Immune Checkpoint Inhibitors

Immune checkpoint inhibitors can cause side effects that are similar to other anti-cancer treatments such as chemotherapy and radiation therapy.

Common Side Effects of Checkpoint Inhibitors

  • Fatigue
  • Cough
  • Nausea
  • Loss of appetite
  • Diarrhea
  • Skin rash
  • Itchy skin

A concern with immune checkpoint inhibitors is that they may cause the immune system to attack healthy cells and organs. Because they serve to stimulate the immune system against cancer, it can lead to serious side effects.

These serious side effects are less common and usually affect the following organs: lungs, liver, intestines, kidneys and the endocrine glands.

Clinical Trials Testing Mesothelioma Immune Checkpoint Inhibitors

The majority of mesothelioma clinical trials testing these drugs involve two immune checkpoint inhibitors. Combining drugs that target different antigens has a synergistic effect.

Some trials combine immune checkpoint inhibitors with chemotherapy or a mesothelioma vaccine.

  • Yervoy and Opdivo

    Positive results from phase I and phase II trials of Yervoy and Opdivo in mesothelioma patients has led to a phase III clinical trial.

    This is significant because phase III trials for mesothelioma are rare. It isn’t common for a therapy to work well enough in a phase II mesothelioma trial to warrant further study. Researchers have high hopes for this study.

  • Imfinzi and Tremelimumab

    Trials of Imfinzi and tremelimumab in mesothelioma patients began in 2016 and 2017. These trials are too new to produce results.

    However, in 2015, an Italian clinical trial that combined these drugs proved clinical activity in mesothelioma, which means the study proved these drugs are effective but did not prove whether the drugs improved survival.

  • Imfinzi and Chemotherapy

    In 2017, the Seattle Cancer Care Alliance opened a phase II clinical trial combining Imfinzi with the chemotherapy drugs cisplatin and pemetrexed (Alitma).

  • Keytruda and Mesothelioma Vaccine CRS-207

    In 2017, the Moffitt Cancer Center in Tampa, Florida, opened a phase II clinical trial combining Keytruda with the mesothelioma vaccine CRS-207. The trial is available at five other cancer centers in the U.S.

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Joining the team in February 2008 as a writer and editor, Michelle Whitmer has translated medical jargon into patient-friendly information at Asbestos.com for more than eight years. Michelle is a registered yoga teacher, a member of the Academy of Integrative Health & Medicine, and was quoted by The New York Times on the risks of asbestos exposure. Read More

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Last Modified June 6, 2018
Sources
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    Retrieved from: http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)
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  8. ClinicalTrials.gov. (2015, October 27). A Study of Tremelimumab Combined With the Anti-PD-L1 MEDI4736 Antibody in Malignant Mesothelioma (NIBIT-MESO-1).  
    Retrieved from: https://www.clinicaltrials.gov/ct2/show/NCT02588131 
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