Immunotherapy for Pleural Mesothelioma: Biomarkers Urgently Needed

A new report says biomarkers are urgently needed to determine which patients would benefit from immunotherapy for pleural mesothelioma. 

Researchers made the statement in a review of immunotherapy drugs in testing for malignant mesothelioma. 

They say some of these drugs have proven to be more effective than others for asbestos cancer. But a set of biomarkers would go a long way to funneling patients into the right immunotherapy for pleural mesothelioma. 

The Status of Immunotherapy for Pleural Mesothelioma

Immunotherapy is believed to be the most promising up-and-coming cancer treatment. Immunotherapy treatments harness the strength of the body’s own immune response to attack cancer or help other drugs do so. 

Like other types of cancer, mesothelioma cells have ways of avoiding detection by the immune system. Immunotherapy drugs like Keytruda (pembrolizumab), Yervoy (ipilimumab), and Opdivo (nivolumab) have all been tried as immunotherapy for pleural mesothelioma. 

These and other immunotherapy drugs have produced mixed results. The authors of the new study say one reason is that doctors do not know which drugs to try in which patients. 

PD-L1 and the Immune System

There are some biomarkers for mesothelioma immunotherapy. The problem is that they are not consistently helpful. Keytruda, IMFINZI (durvalumab) and Opdivo all block a protein called PD-L1. PD-L1 is one of the ways that cancer cells hide from the immune system. 

Patients whose cells express high levels of PD-L1 are most likely to respond to PD-L1-blocking immunotherapy for pleural mesothelioma. But right now, doctors do not know which one is going to work best. 

“PD-L1 inhibitors show response rates between 10 and 29% in phase II trials, with a wide range in progression free and overall survival,” writes study author Cornedine de Gooijer of The Netherlands Cancer Institute. “However, single agent pembrolizumab was not superior to chemotherapy (gemcitabine or vinorelbine) in the recent published PROMISE-Meso trial in pre-treated patients.”

CTLA-4 Blockers as Mesothelioma Immunotherapy

CTLA-4 blockers fall into another category of immunotherapy for pleural mesothelioma. The CTLA-4 protein sends a signal to immune system T-cells not to attack the mesothelioma cells. Yervoy is an example of a CTLA-4 blocker. 

Small studies show some mesothelioma patients respond to CTLA-4 blockers but they do not help them live longer. The study authors say some of the best responses have come from combining a PD-L1 blocker with standard chemotherapy. 

The final type of immunotherapy for pleural mesothelioma reviewed in the article is dendritic cell therapy. MesoPher is an example of dendritic cell therapy. Dendritic cell therapy “reprograms” the patient’s own immune system cells. The authors of the new report say it shows “remarkable anti-tumor activity” in three clinical trials. 

They conclude that checkpoint inhibitors do not help much on their own. They say the key to more effective immunotherapy for pleural mesothelioma is to come up with better combinations of these drugs. 

To do that, they need ways to decide which ones are right for individual patients. 

“There is an urgent need for biomarkers to select the optimal candidates for immunotherapy among MPM patients in terms of efficacy and tolerance,” concludes Dr. de Gooijer. 

Source:

De Gooijer, CJ, et al, “Immunotherapy in Malignant Pleural Mesothelioma”, February 21, 2020, Frontiers in Oncology, https://www.frontiersin.org/articles/10.3389/fonc.2020.00187/full