Mesothelioma Treatment: Hopkins Immunotherapy Trial

A phase 2 trial from Johns Hopkins has demonstrated that giving immunotherapy drugs both before and after mesothelioma surgery is safe and effective. The study, published in Nature Medicine on September 8, 2025, found that combination immunotherapy produced a median overall survival of 28.6 months, a 59% improvement over the historical average of approximately 18 months. The results were also presented at the World Conference on Lung Cancer in September 2025.

The finding is significant because treatment options for people with operable mesothelioma have remained limited for decades. This trial tested a perioperative approach, meaning immunotherapy was given in two phases: before surgery to shrink the tumor and prime the immune system, and after surgery to target any remaining cancer cells.

How the Trial Worked

Patients enrolled in the trial received nivolumab (Opdivo) alone or combined with ipilimumab (Yervoy) for six weeks before surgery. After surgical removal of the tumor, they continued nivolumab for up to one year. The trial enrolled people with operable (resectable) diffuse pleural mesothelioma at Johns Hopkins and collaborating institutions, including Georgetown University.

The research team was led by Dr. Valsamo Anagnostou, Alex Grass Professor of Oncology at the Johns Hopkins Kimmel Cancer Center, alongside Dr. Julie Brahmer, co-director of the Bloomberg-Kimmel Cancer Immunotherapy Institute, and Dr. Joshua Reuss from Georgetown University.

“This is the first published clinical trial to show that perioperative combination immune checkpoint blockade is not only feasible but potentially beneficial in resectable mesothelioma,” Dr. Anagnostou said.

Survival and Response Rates

Patients who received the combination therapy (nivolumab plus ipilimumab) lived a median of 28.6 months. That compares favorably to the historical average of roughly 18 months for people with operable mesothelioma receiving standard treatment. Nearly 36% of combination-treated patients remained alive and recurrence-free at follow-up.

Over 80% of trial participants successfully underwent surgery within the planned window after receiving pre-operative immunotherapy. This is an important finding because one concern with neoadjuvant (pre-surgery) treatment is that side effects could delay or prevent the operation. The trial showed that the immunotherapy regimen did not meaningfully interfere with surgical timing. Side effects remained manageable across both treatment groups, with low rates of serious complications.

The approach mirrors protocols already used successfully in lung cancer, where perioperative immunotherapy has improved outcomes. This trial provides the first rigorous evidence that the same strategy can benefit people with mesothelioma.

Liquid Biopsy: A Blood Test That Sees What Imaging Misses

One of the trial’s most notable innovations was the incorporation of an ultra-sensitive liquid biopsy that detects circulating tumor DNA (ctDNA) in the bloodstream. Mesothelioma tumors carry relatively few genetic mutations compared to other cancers, making them historically difficult to track with standard blood tests. The Hopkins team used a whole-genome sequencing method to overcome that limitation.

The results were clinically significant. Patients whose ctDNA became undetectable after pre-operative immunotherapy, or whose levels dropped by 95% or more, experienced significantly longer survival and longer periods without cancer recurrence. Conversely, patients with persistent ctDNA were more likely to experience early disease progression, even when their imaging scans appeared normal.

“Imaging doesn’t always capture what’s happening with mesothelioma, especially during treatment,” Dr. Anagnostou explained. “By using an ultra-sensitive genome-wide ctDNA sequencing method, we were able to detect microscopic signs of cancer that imaging missed.”

This capability could eventually allow doctors to make more personalized treatment decisions, identifying which patients need additional therapy after surgery and which may safely forgo it.

What These Findings Mean

These results are preliminary but promising. They provide a foundation for larger confirmatory trials that could establish perioperative immunotherapy as standard care for people with mesothelioma eligible for surgery. The ctDNA monitoring approach could also become a valuable tool for guiding treatment decisions in real time, rather than relying solely on periodic imaging scans.

For people with mesothelioma and their families, the trial represents a meaningful step forward for a disease that has historically resisted treatment advances. The combination of improved survival numbers, manageable side effects, and a new molecular monitoring tool addresses several longstanding challenges in mesothelioma care.