A landmark trial from Johns Hopkins has demonstrated that giving immunotherapy drugs before and after mesothelioma surgery is both safe and effective—a finding that could reshape treatment for patients whose tumors can be surgically removed.
The phase 2 study, published in Nature Medicine and presented at the World Conference on Lung Cancer in September 2025, tested a combination approach: patients received nivolumab (Opdivo) alone or paired with ipilimumab (Yervoy) for six weeks before surgery, then continued nivolumab for up to a year afterward. The results mark the first time this so-called “perioperative” immunotherapy strategy has been rigorously tested in mesothelioma—a rare, aggressive cancer linked to asbestos exposure.
“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,” says Dr. Valsamo Anagnostou, the study’s senior author at Johns Hopkins. The approach mirrors successful protocols already used in lung cancer, where immunotherapy before surgery has improved outcomes.
Strong Survival Signals From Early Data
Patients who received the combination therapy (nivolumab plus ipilimumab) lived a median of 28.6 months—significantly longer than the historical average of 18 months for mesothelioma. Nearly 36% of combination-treated patients remained alive and recurrence-free at follow-up, a meaningful improvement that suggests the strategy works for at least a subset of patients.
Over 80% of trial participants successfully underwent surgery within the planned window after receiving pre-operative immunotherapy, demonstrating the approach doesn’t delay or prevent surgical intervention. Side effects remained manageable across both treatment groups, with low rates of serious complications—an important safety benchmark for any new cancer treatment.
A Blood Test That Sees What Imaging Misses
Perhaps equally important, the trial incorporated an innovative monitoring tool: an ultra-sensitive liquid biopsy that detects circulating tumor DNA (ctDNA) in the bloodstream. Mesothelioma tumors carry few genetic mutations, making them historically difficult to track with standard blood tests. This new whole-genome sequencing method overcomes that limitation.
The clinical payoff is substantial. 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—information that could prompt doctors to adjust treatment sooner.
“Imaging doesn’t always capture what’s happening with mesothelioma, especially during treatment,” Anagnostou explains. “By using an ultra-sensitive genome-wide ctDNA sequencing method, we were able to detect microscopic signs of cancer that imaging missed.”
What Comes Next
These preliminary findings provide a foundation for larger confirmatory trials. If the benefits hold up in broader populations, the combination approach could become standard care for mesothelioma patients eligible for surgery—a population that currently faces few effective options. The ctDNA monitoring strategy may also enable personalized treatment decisions, helping doctors identify which patients need additional therapy and which can safely avoid it.
For mesothelioma patients and families, the trial offers a rare bright spot in a disease that has resisted treatment advances for decades.