Study Implies Future Immunotherapy Success in Peritoneal Mesothelioma

The gloved hand of a researcher places a slide onto the viewing stage of a microscope. The slide contains tissue from a peritoneal mesothelioma tumor.

Recently, the mesothelioma community has been brimming with good news about immunotherapy. For example, one duo of immune checkpoint inhibitor (ICI) drugs more than doubled survival for some patients. This treatment has only been vetted in pleural mesothelioma. Doctors do not yet know its efficacy in treating peritoneal mesothelioma patients. But a recent study from Rutgers University may shed some light on this topic.

Mesothelioma is an asbestos-linked cancer that occurs in the linings of some tissues and organs. Pleural mesothelioma occurs in the lining around the lungs. Peritoneal mesothelioma arises in the lining surrounding the abdomen. The rarest forms of this cancer can occur in the lining around the heart or the testicles.

The team at Rutgers ran tests to estimate how peritoneal mesothelioma might respond to ICI drugs. Their results suggest peritoneal tumors may be responsive to ICI drugs.

Study Researchers Checked Biopsy Tissue for Immune Checkpoint Proteins

Rutgers researchers tested peritoneal mesothelioma tumors for a specific protein called PD-L1. PD-L1 forms one half of the PD-1/PD-L1 immune checkpoint. Tumor cells can make PD-L1 and use it to disguise tumors to look like healthy tissue. That causes immune cells to not attack tumors.

ICI drugs block cancer cells from using this trick. This allows immune cells to attack tumors. In the past, this strategy has been effective against cancers that make PD-L1 protein.

Immune checkpoints are safeguards within the immune system. They work like a handshake that tells immune cells to ignore healthy cells. Healthy cells have proteins (like PD-L1) that “shake hands” with checkpoint proteins (like PD-1) on immune cells. When this interaction occurs, immune cells know not to attack their handshake partners. But cancer cells can make PD-L1 and use it to keep immune cells from attacking. Checkpoint inhibitor drugs help prevent them from doing this.

Testing for these protein markers can help identify cancers likely to respond to ICIs. If a tumor biopsy sample tests positive for PD-L1 protein, the tumor has a good chance of responding to ICI treatment.

Peritoneal Biopsy Tissue Tested Positive for Predictor of ICI Response

The Rutgers team tested 21 peritoneal mesothelioma samples for PD-L1 protein. More than 75% tested positive. This means the tumors may be using PD-L1 to dodge attacks from immune cells. It also means ICI treatment may help these patients.

Senior study author H. Richard Alexander, Jr., MD, FACS was optimistic about these results.

“We are excited for checkpoint inhibition to be an effective treatment option for patients with this rare cancer.”

 - H. Richard Alexander, Jr., MD, FACS

Dr. Alexander and other researchers plan to continue exploring this treatment with another study.

Do Drugs That Work for Pleural Mesothelioma Also Work for Peritoneal Cases?

The U.S. Food and Drug Administration (FDA) approved an ICI combo for inoperable pleural cases in late 2020. Because of this, some may assume they will work equally well in other types of mesothelioma. But according to experts, such an assumption could turn out to be wrong.

Which immunotherapy has FDA approval for treating pleural mesothelioma? The checkpoint inhibitor duo of Opdivo® (nivolumab) and Yervoy® (ipilimumab) is FDA-approved for inoperable pleural mesothelioma. These drugs more than doubled survival for patients with PD-L1-linked tumors.

Travis Grotz, MD, spoke recently about the differences between mesothelioma types and how they affect interpretation of study results. He said they are “different tumors with different biologies.”

If pleural mesothelioma responds well to a treatment, doctors still don’t know if the treatment will work as well in peritoneal cases. A successful pleural mesothelioma study does not guarantee a similarly successful study in peritoneal cases.

So it remains unclear whether the success of Opdivo+Yervoy for pleural mesothelioma will translate to peritoneal cases. More research may help clarify this question. In the meantime, the Rutgers research may provide reason to hope.

Rutgers Study Hints at Checkpoint Inhibitor Efficacy for Peritoneal Mesothelioma

The Rutgers study tested peritoneal mesothelioma tumors for checkpoint proteins and found them. In fact, the percentage of tumors with these proteins was higher than that of pleural tumors tested in a prior study. According to experts, this kind of testing is a promising predictor of how tumors will respond to ICI therapy.

This might mean that ICI therapy could be even more effective for peritoneal patients than pleural. More research is needed to answer this and other questions about ICI therapy.

What Does This Mean for Mesothelioma Patients?

Peritoneal mesothelioma patients may have a new treatment option down the road, but it is still a bit too soon to tell. Researchers will likely do larger studies, possibly comparing ICI treatment to chemotherapy. The results of those studies will give doctors and regulators a better understanding of ICI drugs. In the meantime, peritoneal mesothelioma patients may be able to access ICI therapy through clinical trials.