Predicting effectiveness of mesothelioma immunotherapy

• Maja Belamaric
• Featured News

In recent years, immunotherapy has revolutionized cancer treatment for most cancers, and even the notably difficult-to-treat mesothelioma has reaped benefits. However, despite two new FDA treatment approvals featuring immunotherapy, this treatment only works for a minority of mesothelioma patients and the benefit is most obvious in the most aggressive, sarcomatoid group.  This fact, paired with concerns of immune toxicity, can make some patients and physicians wish they had more tools to gauge if immunotherapy will be more useful than harmful. But are we able to predict its effectiveness before starting treatment?

Drs. Farhad Kosari and Maria Disselhorst of the Mayo Clinic, among others, have been studying exactly this problem. In their paper “Tumor Junction Burden and Antigen Presentation as Predictors of Survival in Mesothelioma Treated with Immune Checkpoint Inhibitors” published in the Journal of Thoracic Oncology, the authors conclude that an analysis of tumor genetics for mutations may facilitate patient selection for immunotherapy treatments based on checkpoint inhibitors.

Why is mesothelioma so difficult to treat?

There are many reasons for mesothelioma’s resistance to treatment. When it comes to the immune system’s role in this cancer’s proliferation, patients may hear researchers discuss its “low mutation burden.” What this means is that the cancer cells don’t look that different from the body’s non-cancerous cells on a genetic level. In other words, the number of gene mutations in a mesothelioma tumor are so few that the tumor looks like a normal cell to the immune system, which is in part how it evades it.

Based on scientific studies, the tumor mutation burden generally predicts the effectiveness of the immune checkpoint inhibitor therapy used for other cancers. The more mutations there are on the tumor that differentiate it from normal tissue, the easier it is for the primed immune system to see it and attack it, and the easier it is to target the tumor with therapies.

The flipside of this, of course, is that with mesothelioma that’s not the case, which begs the question: why do some mesothelioma patients respond to immunotherapy, while others don’t? What is so different about the ones who respond?

Tumor junction burden and antigen presentation as predictors of survival in mesothelioma

Researchers looked at 68 patients who had been treated with nivolumab and ipilimumab and nivolumab alone. Of these patients, 44 had sufficient DNA and RNA content derived from biopsy to be part of this analysis. What they concluded is that patients with a high tumor junction burden and antigen presentation survived longer than those without suggesting that it may be possible to use this information to select which patients might benefit from immunotherapy.

As mesothelioma treatment continues to head in the direction of targeted therapies, the expectation is that molecular and genetic knowledge acquired over the last decade will be incorporated into new generation treatment paradigms so doctors and patients can make fully informed decisions about treatment based on each individual patient’s circumstances.