Who Responds Best to Mesothelioma Immunotherapy Treatment?

Immunotherapy for mesothelioma works, just not in every case.

The goal is to determine who will benefit from this emerging therapy — and who won’t.

The National Cancer Institute (NCI) awarded a $2.5 million grant to Baylor College of Medicine for an immune checkpoint inhibitor study. Dr. Bryan Burt, the chief of thoracic surgery at Baylor St. Luke’s Medical Center, is leading the study. It’s officially titled “Proteomic Determinants of Response to Checkpoint Blockade in Malignant Pleural Mesothelioma.”

Dr. Burt, a mesothelioma specialist, wants to develop a test to determine which patients would respond to immune checkpoint inhibitors. It’ll protect people who won’t respond to the treatment from immunotherapy-related side effects.

“We want to be able to predict not only who is going to respond, but also the strength of the response,” Dr. Burt said in a press release on the Baylor College of Medicine website.

“In other words, whether the tumor will completely or partially shrink or just remain stable for long periods of time, which is important too. We hope to design a test that would allow us to predict those possible outcomes.”

 

Baylor College of Medicine Study on Checkpoint Inhibitors

The test requires an examination of malignant mesothelioma tissue, specifically the genetics.

Cancer forms due to genetic changes at the cellular level. Mesothelioma is no different, forming when asbestos fibers irritate cells and affecting the DNA.

Since genes are involved, each mesothelioma case is at least a little different than all others. Some patients have different levels of cancerous genes than others, and this can dictate how patients respond to treatment.

“Preliminary data collected retrospectively showed that the tumors of patients who respond to (immune checkpoint inhibitors) tend to have a certain cell composition, which is quite complex,” Dr. Burt said in the press release.

So he developed a test to analyze 30 cell types in miniscule tumor samples. Dr. Burt also will look at the architecture and organization.

Another element is the level of cancerous proteins, or neoantigens, in the cancer. Tumor surface molecules block immune system T-cells from defending against cancer.

Dr. Burt will also look for molecules called MHC, which deliver neoantigens to the immune system and quicken the response from T-cells.

“We have found that when both neoantigens and certain MHC molecules are there, the patient responds well to the therapy,” Dr. Burt said in the press release.

 

Checkpoint Inhibitors for Mesothelioma

Three immune checkpoint inhibitors for mesothelioma are Opdivo (brand name of nivolumab), Yervoy (ipilimumab) and Keytruda (pembrolizumab).

The U.S. Food and Drug Administration (FDA) approved Opdivo and Yervoy together for unresectable mesothelioma cases. It has an average survival of 18.4 months, which is better than chemotherapy.

The FDA also approved Keytruda in cases with high levels of PD-L1, the cancerous protein that stifles the immune system. The Baylor College of Medicine study follows the mentality that some, not all, mesothelioma cases should get immunotherapy.