Peritoneal Mesothelioma Immunotherapy

How Does Immunotherapy for Cancer Work?

Immunotherapy is a class of cancer treatment that elevates the immune system’s response to cancer cells. Peritoneal mesothelioma cancer cells use different mechanisms to shut down the immune system and avoid attack from immune cells. Immunotherapy can reverse these activities.

One of the biggest benefits of immunotherapy is it doesn’t harm healthy tissue like chemotherapy, and therefore does not cause as severe of side effects.

The FDA has not yet approved any immunotherapy drugs for the treatment of peritoneal mesothelioma, but many peritoneal mesothelioma specialists support the use of this treatment option.

“For thoracic mesothelioma, there has been a recent advance in terms of using immunotherapy, which likely is going to be an opportunity for patients with peritoneal mesothelioma as well,” said Dr. Edward Levine, a peritoneal mesothelioma surgeon at Wake Forest Baptist Cancer Center.

How Does Immunotherapy Help the Immune System?

The human immune system is complex, and each part plays an important role in keeping our bodies healthy and safe from viruses and diseases, including cancer. The different components helping fight peritoneal mesothelioma are:

• Antigens – Foreign invaders, such as a virus, and could also refer to proteins on cancer cells (tumor antigens)
• Antibodies – Proteins that mark cancer cells for the T cells to attack
• T cells – The security guards of the immune system, tasked with attacking and eliminating cancer cells
• B cells – Cells that produce antibodies to defend against antigens
• Dendritic cells – Cells that download information about cancer cells and deliver the information to T cells

The presence of antigens alerts the immune system and initiates an immune response. The immune system signals for B cells to produce antibodies.

Once the antibodies attach to the peritoneal mesothelioma cell, T cells can identify and eliminate the diseased cells. Immunotherapy can send signals to B cells to produce more antibodies or improve the response of T cells.

Side Effects of Peritoneal Mesothelioma Immunotherapy 

Peritoneal mesothelioma immunotherapy is still an experimental treatment, but some scientists believe it is better for patients than chemotherapy. Immunotherapy usually has less severe side effects than chemotherapy.

Side effects of peritoneal mesothelioma immunotherapy may include: 

Checkpoint Inhibitor Immunotherapy for Peritoneal Mesothelioma

There are two main types of checkpoint inhibitor drugs for peritoneal mesothelioma:

• PD-1/PD-L1 inhibitors
• CTLA-4/B7 inhibitors

Both work in a similar manner. They block the connection of a protein on the surface of peritoneal mesothelioma cells with a protein on the surface of T cells. The connection of these proteins causes T cells to become less effective at finding and attacking mesothelioma.

“I think there’s an opportunity and (immunotherapy) has to be part of the conversation,” said Dr. Shanel Bhagwandin, a peritoneal mesothelioma surgeon at Jupiter Medical Center.

PD-1/PD-L1 Checkpoint Inhibitors

PD-1 stands for programmed cell death protein 1. It is a protein on the surface of T cells. PD-L1 stands for programmed death-ligand 1. It is a protein on the surface of peritoneal mesothelioma cells.

When PD-1 connects with PD-L1 the T cells are essentially shut down, which means the T-cells cannot identify and attach the mesothelioma cancer cells. PD-1/PD-L1 checkpoint inhibitors block or break the protein binding and activates the T cells to attach the  mesothelioma cells.

PD-1/PD-L1 checkpoint inhibitors for peritoneal mesothelioma include:

• Keytruda, brand name for pembrolizumab
• Opdivo, brand name for nivolumab

CTLA-4/B7 Checkpoint Inhibitors

CTLA-4 is a protein on the surface of T cells, while B7 is a protein on the surface of mesothelioma cells. These two also can bind and shut down T cells. CTLA-4/B7 checkpoint inhibitors act as a wall between the two and can activate the T cells.

The main example of a CTLA-4/B7 checkpoint inhibitor for mesothelioma is Yervoy, the brand name for ipilimumab.

Immunotherapy Drugs in Testing for Peritoneal Mesothelioma

There are a few peritoneal mesothelioma immunotherapy drugs in testing through clinical trials. One of them is apatinib, which is an anti-VEGF therapy that blocks the creation of blood vessels to provide tumors the oxygen and other nutrients they need.

In the clinical trial, the median overall survival was 59.4 months (nearly five years) and the overall response rate was 60%, meaning 3 out of every 5 patients had a positive tumor response to the immunotherapy.

The others are Opdivo, Yervoy and Keytruda. These three are all FDA-approved in some form for pleural mesothelioma, but they are not yet approved for peritoneal mesothelioma.

“We are trying immunotherapy in combination with traditional chemotherapy,” said Dr. Deepa Magge, the head of Vanderbilt University Medical Center’s peritoneal mesothelioma treatment. “There is going to be a trial. We just discussed this at one of the conferences. They do want to figure out a good trial for peritoneal mesothelioma for immunotherapy.”

Opdivo and Yervoy for Peritoneal Mesothelioma

A study at MD Anderson Cancer Center featured the immunotherapy drugs Opdivo and Yervoy for peritoneal mesothelioma. They led to an overall median survival of 19 months, the 1‑year survival rate was 68%, and the disease control rate was 65%. All three of these results are better than chemotherapy or no treatment at all.

A study at the University of Chicago Medicine started enrolling peritoneal mesothelioma patients in 2021 and features Opdivo and Yervoy. Patients receive the combination therapy prior to their cytoreduction and HIPEC surgery.

Another clinical trial is testing Opdivo and Yervoy before and after peritoneal mesothelioma surgery.

Keytruda for Peritoneal Mesothelioma

In a study published in 2023, the immunotherapy drug Keytruda was credited for a peritoneal mesothelioma survival average of 21 months. There were 24 patients in the study and all but one had a previous cycle of systemic chemotherapy. Two-thirds (16 of 24) underwent cytoreductive surgery with HIPEC.

One case of a 59-year-old man diagnosed with peritoneal mesothelioma had outstanding results thanks to Keytruda. The immunotherapy led to a complete response (meaning no signs of cancer in imaging scans), and the patient has been cancer-free for four years at the time of the case report in the medical journal Cureus.

These results are further proof of why medical experts believe there’s a future of using immunotherapy for peritoneal mesothelioma.

“I think there is a future for (immunotherapy). The data is sparse at best,” said Dr. Joel Baumgartner, a surgical oncologist at Moores Cancer Center at UC San Diego Health. “The earliest studies included just a handful of peritoneal patients among the many pleural patients.”