Study Highlights Challenge of Selecting Patients for Mesothelioma Immunotherapy

A new study is casting some doubt on the value of a protein called PD-L1 as a way to select mesothelioma patients for targeted immunotherapy.

Several of the most promising new treatments for malignant mesothelioma, including pembrolizumab (Keytruda) and avelumab (Avastin), are designed to inhibit PD-L1, a protein cells used to evade detection by the immune system.

PD-L1 inhibitors like Keytruda have become an important focus of mesothelioma research in the past two years.

But a new Mayo Clinic study suggests that PD-L1 may not be the miracle target that scientists and mesothelioma patients have been hoping for. That is because PD-L1 levels can sometimes vary widely, depending on when and from where the tissue samples were collected.

PD-L1 Expression in Malignant Mesothelioma

In a new article in the medical journal Oncoimmunology, a team made up of Mayo Clinic pathologists, oncologists, urologists, immunologists, and pulmonary medicine specialists analyzed the pathology files on patients diagnosed with either pleural or peritoneal mesothelioma between 1995 and 2016.

Most of the study subjects were men and most had the epithelioid form of mesothelioma, which is the most common variety worldwide.

To be included in the study, the patients had to have had either a second tissue sample taken from their primary mesothelioma tumor at a separate time, or from a metastatic tumor, or both.

Levels Consistent in Most Mesothelioma Patients

In most cases, the PD-L1 expression was consistent between separate samples taken from the same patients, regardless of when or from which tumor they were taken.

However, in about 20 percent of cases, the PD-L1 level had changed when the same tumor was checked at a different time, or when tumors from different sites were compared to each other. The researchers say these differences make it difficult to rely on PD-L1 for planning and implementing effective mesothelioma treatment.

“Overall there is good agreement in PD-L1 expression between paired malignant mesothelioma lesions,” writes Mayo Clinic pathologist Simone BSP Terra. “However, the 19-31% of cases with discordant PD-L1 expression, and the dynamics of PD-L1 expression, may limit its use as a predictive biomarker for therapy.”

PD-L1 and Mesothelioma Survival

A recent Australian study found that 72.4% of mesothelioma patients overexpressed PD-L1, and that these patients had a significantly shorter mesothelioma survival rate than other patients. Other recent studies also support the idea that mesothelioma patients who overexpress PD-L1 are less likely to survive the asbestos cancer than those who produce less.

Although the current study does not address the value of PD-L1 as a predictor of mesothelioma survival, the fact that PD-L1 levels can fluctuate, even in the same patient, suggests that it may not be as reliable as previously thought.

Sources:

Terra, SBSP, et al, “Temporal and spatial heterogeneity of programmed cell death 1-Ligand 1 expression in malignant mesothelioma”, July 27, 2017, Oncoimmunology

Nguyen, BH, “PD-L1 expression associated with worse survival outcome in malignant pleural mesothelioma”, November 3, 2017, Asia Pacific Journal of Clinical Oncology, Epub ahead of print