A phase 2 trial from Johns Hopkins has demonstrated that giving immunotherapy drugs before and after mesothelioma surgery is both safe and effective, producing a 59% improvement in median survival over historical averages. The findings, published in Nature Medicine on September 8, 2025, and presented at the World Conference on Lung Cancer, could reshape treatment for the subset of people with mesothelioma whose tumors can be surgically removed.
The trial tested a perioperative approach: patients received nivolumab (Opdivo) alone or combined with ipilimumab (Yervoy) for six weeks before surgery, then continued nivolumab for up to one year afterward. This marks the first time this strategy has been rigorously tested in mesothelioma.
Survival Numbers
Patients who received the combination therapy (nivolumab plus ipilimumab) lived a median of 28.6 months, compared to the historical average of approximately 18 months for people with operable mesothelioma. 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, demonstrating that the approach does not delay or prevent surgical intervention. 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 evidence that the same strategy can benefit people with mesothelioma.
“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,” said Dr. Valsamo Anagnostou, the study’s senior author and Alex Grass Professor of Oncology at the Johns Hopkins Kimmel Cancer Center.
A Blood Test That Sees What Imaging Misses
The trial incorporated an innovative monitoring tool: an ultra-sensitive liquid biopsy that detects circulating tumor DNA (ctDNA) in the bloodstream using whole-genome sequencing. Mesothelioma tumors carry few genetic mutations, making them historically difficult to track with standard blood tests. This method overcomes that limitation and represents the first use of tumor-informed liquid biopsy in operable mesothelioma.
The clinical implications are significant. Patients whose ctDNA became undetectable after pre-operative immunotherapy, or whose levels dropped 95% or more, experienced significantly longer survival and longer periods without cancer recurrence. Conversely, persistent ctDNA predicted early disease progression even when imaging scans appeared normal, providing doctors with information that could prompt earlier treatment adjustments.
Traditional imaging often fails to detect microscopic mesothelioma. This liquid biopsy uses ultra-sensitive whole-genome sequencing to find fragments of tumor DNA circulating in the blood. By comparing blood samples taken before, during, and after treatment, doctors can determine whether immunotherapy is working at a molecular level, even when scans look normal.
Study Design and Participants
The trial enrolled people with operable (resectable) diffuse pleural mesothelioma at Johns Hopkins and collaborating centers, including Georgetown University. Patients were randomized to receive either nivolumab alone or nivolumab combined with ipilimumab during the pre-operative phase. The research team was led by Dr. Anagnostou alongside co-director Dr. Julie Brahmer and Dr. Joshua Reuss from Georgetown.
Key design features:
- Pre-operative phase: Six weeks of immunotherapy before surgery
- Surgery: Pleurectomy/decortication or extrapleural pneumonectomy
- Post-operative phase: Up to one year of maintenance nivolumab
- Monitoring: Serial ctDNA measurements and standard imaging
What Comes Next
These findings provide a foundation for larger confirmatory trials. If the benefits hold up in broader populations, the perioperative combination approach could become standard care for the subset of people with mesothelioma eligible for surgery, a population that currently faces limited effective options.
The ctDNA monitoring strategy may also enable more personalized treatment decisions, helping doctors identify which patients need additional therapy after surgery and which may safely forgo it, avoiding unnecessary treatment and its side effects.
What did the Johns Hopkins mesothelioma trial find?▼
The phase 2 trial found that giving immunotherapy (nivolumab and ipilimumab) before and after mesothelioma surgery is safe and effective. Patients receiving combination therapy achieved 28.6-month median survival, a 59% improvement over the historical 18-month average. Nearly 36% of combination patients were alive and recurrence-free at follow-up.
What is perioperative immunotherapy?▼
Perioperative immunotherapy means giving immune checkpoint inhibitor drugs both before surgery (neoadjuvant) and after surgery (adjuvant). In this trial, patients received nivolumab alone or with ipilimumab for six weeks before their mesothelioma surgery, then continued nivolumab for up to one year afterward. The approach has already proven effective in lung cancer.
What is the ctDNA liquid biopsy?▼
The trial used an ultra-sensitive blood test that detects tiny fragments of tumor DNA circulating in the bloodstream using whole-genome sequencing. This liquid biopsy can identify cancer that standard imaging misses. Patients whose tumor DNA became undetectable after immunotherapy had significantly better survival outcomes.
Who is eligible for this treatment approach?▼
The trial enrolled people with operable (resectable) diffuse pleural mesothelioma. Not all people with mesothelioma are candidates for surgery. Eligibility depends on the stage of disease, tumor location, overall health, and lung function. A thorough evaluation at a specialized mesothelioma center can determine whether surgical options are appropriate.