New Strategy for Difficult Therapy Mesothelioma: Immunotherapy and CTDNA Insights

People with diffuse pleural mesothelioma can benefit from immunotherapy before and after surgery, based on the results of a clinical trial investigating the treatment sequence and the role of surgery so it is difficult to cure cancer.

Mesothelioma is a rare cancer that affects the tissue that aligns many organs of the body. About 30,000 cases are diagnosed each year worldwide, most of them in the pleura or lung lining. It occurs more frequently in people who have been exposed to asbestos.

“Mesothelioma is a difficult tumor for treatment,” said lead author Joshua Reuss, MD, thoracic medical oncologist with the integrated Lombardi Cancer Center in Georgetown. “Our study has shown the feasibility and safety of the use of immunotherapy before surgery for patients who may be surgically removed.

“Immunotherapy contributes significantly to the expansion of the lives of patients with lung cancer and many other solid tumors. This is an important step in detecting patients that could benefit from immunotherapy at hospital and hospital hospital.”

Reuss designed the clinical trial during a scholarship at Johns Hopkins Kimmel Cancer Center, the primary space where the study was conducted. Presented the results of Phase II, Neoadjuvant Nivolumab or Nivolumab Plus ipililumab on a re -extensive diffuse mesothelium, at the World Congress of 2025 on Lung Cancer in Barcelona, ​​Spain on September 8 and is the leader of the author of the study published at the same time Natural medicine (DOI 10.1038/S41591-025-03958-3).

Phase II clinical trials are designed to evaluate if it is possible to provide innovative treatments to specific patient populations and whether the potential benefits of treatment compensate for any adverse effects that patients face.

“When we look at the results of patients to date, the question of whether any mesothelioma is truly constant is controversial,” Reuss said. “Several important studies have not shown improvement in survival when surgery is incorporated into systemic treatment for mesothelioma. This study incorporates immunotherapy into patients who may benefit from surgery.

“Since they appear in the tissue that defines the lungs, the mesotheliomas do not grow and spread like other cancers.” Said Reuss. “They do not formally form solid masses or nodules. These tumors are more fluid or pervasive throughout the lung lining, which makes it more difficult to use our usual methods to determine how extensive the tumor is or to measure if a treatment is effective.

In this study, the clinical team worked closely with scientists in the laboratory to test a new approach that is studying circulated DNA volume (CTDNA) in their patient’s blood. Tumors often drop the DNA of blood cancer. Oncologists can test the blood to detect the presence of this CTDNA, but their role in clinical decision -making is an evolving area of ​​interest. This is particularly difficult in mesothelioma, a type of tumor that has a low number of cancer mutations that can be detected with traditional CTDNA techniques.

“Imaging does not always record what is happening with mesothelioma, especially during treatment,” said senior study author, Valsamo Anagnostou, MD, PhD, professor Alex Grass oncology and co-director of the Upper Aerodigestive Cancers program at Johns Hopkins. “Using an extremely sensitive CTDNA sequence method at genome level, we were able to detect tiny signs of cancer that the imaging lost and predicts which patients were more likely to benefit from treatment or recurrence of experience.”

“This approach can give us a basic line to watch the effectiveness of this treatment,” Reuss said. “If CTDNA decreases or disappears. It is a good indication that treatment works, if not, shows that a change in treatment can be justified.” Reuss added that further validation of this methodology is needed before it can be systematically integrated into clinical practice.

These analyzes contribute to our understanding of which mesothelioma patients may be candidates for surgery. So far, CTDNA evaluations are not part of the clinical landscape in the management of diffuse mesothelioma, but our analyzes suggest that this may be approaching a change in the future. “

Joshua Reuss, MD, chief author of the study, thoracic medical oncologist with the full cancer of Georgetown Lombardi

Phase II clinical trials are not designed to measure the clinical efficacy of treatment options, but both arms of this test showed improvements in time from treatment to when tumors began to grow again and the overall duration of survival.

Reuss warns against drawing conclusions about these data, but notes that the results provide positive signals about the possible value of neo -adolescent immunotherapy for patients with tumors that can be surgically removed and show the way to future studies.

“This is a small study,” he said, “and does not tell us if new -business immunotherapy will improve the results for these patients, but opens opportunities.

The study was conducted in multiple academic cancer centers. The trial was funded by Bristol Myers Squibb. The survey was partially supported by Congress of Congress of the Department of Defense, Grant CA190755 Medical Research Programs, Johns Hopkins Kimmel Cancer Center NCI Support Grant NCI CCSG P30 CA006973, US Administration and the Administration U01FD005942-FDA, National Institutes Health Grant CA12113, The Bloomberg ~ Kimmeltish for Cancerother, The Thoracic Misses ECOG-ACRin Integrated Translation Sciences Grant UG1CA233259 Commonwealth Foundation, the Mark For Cancer Research Foundation and Florence Lomax Eley Fund.

Reuss reports receive research funding through the University of Georgetown from Genentech/Roche, Verastem, Nuvalent, Arcus, Revolution Medicines, Regeneron, Amgen, Dualitybio and Astrazeneca and Regeneron. Summit Therapeutics, Pfizer, Lilly, Natera, Merck, Emd Serono, Roche Diagnostics and Oncohost. Anagnostou reports receiving funding from Astra Zeneca and the diagnosis of personal genomes, Bristol-Myers Squibb and Delfi Diagnostics, are consultant to Astra Zeneca and Neogenomics and receives Honoraria from his Medicine Personal genome diagnostics. Other authors’ revelations are included in the manuscript.

Additional authors include Paul K. Lee, Reza J. Mehran, Chen Hu, Suqi Ke, Amna Jamali, Mimi Najjar, Noushin Niknafs, Jaime Wehr, Ezgi One, Qiong Meng, Gavin Pereira, Samira Hosseini, Mark Sausen, Marian Zahurak, Rushard, Russellano Hales, Joseph Friedberg, Boris Sepesi, Julie S. Deutsch, Tricia Cottrell, Janis Taube, Peter B. Illei, Kellie N. Smith, Drew M. Pardoll, Anne S. Tsao, Julie R. Brahmer and Patrick M. Forde.