Immunotherapy for Mesothelioma: Who Are the Best Candidates?

Immunotherapy is emerging as one of the most promising new treatment approaches for a wide range of cancers, including malignant pleural mesothelioma, the treatment-resistant lung-related cancer caused by asbestos exposure.

Every year, more than 2,500 Americans are diagnosed with pleural mesothelioma. Most will die of the illness within 18 months, even with the most advanced chemotherapeutic, radiotherapeutic, and surgical treatments.

But immunotherapy, which recruits the body’s own immune system to help fight the cancer, may be a more effective option for some mesothelioma patients.

Now, a new study conducted by researchers in Italy, with support from California-based Genentech, suggests that there may be a way to identify which mesothelioma patients are most likely to benefit from immunotherapy.

Molecular and Histopathological Testing

The secret to identifying good candidates for mesothelioma immunotherapy, say the researchers, lies in analysis of gene expression, either in the mesothelioma tumor cells themselves or in the immune system cells that infiltrate the tumor.

Using tumor samples from 99 people with advanced malignant pleural mesothelioma, the team used a gene analysis tool called NanoString to test for 800 different genes.

They discovered that mesothelioma tumors could be categorized into three different subgroups, and that two of those groups had certain genetic characteristics that might make them more responsive to cancer immunotherapy.

“These data suggest that 60% of MPM patients characterized by either PD-L1 expression or an inflamed status present an attractive candidate for cancer immunotherapeutic options,” writes lead researcher Namrata Patil in a summary of the study in the Journal of Thoracic Oncology.

PD-L1 Expression and Mesothelioma Outcomes

Other recent mesothelioma studies have also focused on the significance of the PD-L1 protein. The KEYNOTE trial of the immune checkpoint inhibitor pembrolizumab (Keytruda), which blocks PD-L1, produced an overall response rate among mesothelioma patients of 20 percent.

PD-L1 blocker avelumab produced a mesothelioma control rate of 56.6% and previously-treated Dutch mesothelioma patients given the immune checkpoint inhibitor nivolumab had a median survival of more than a year.  

Malignant pleural mesothelioma is a rare and highly invasive cancer. The current median survival time with standard cancer treatment is less than 12 months.

Sources:

Patil, NS, et al, “Molecular and Histopathological Characterization of the Tumor Immune Microenvironment in Advanced Stage of Malignant Pleural Mesothelioma”, Octber 24, 2017, Journal of Thoracic Oncology, Epub ahead of print

Thapa, B, et al, “Immunotherapy for malignant mesothelioma: reality check”, October 2016, Expert Review of Anticancer Therapy, Epub ahead of print