Toxicities Potentially Linked to Combination Immunotherapy for Mesothelioma

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The combination of ipilimumab and nivolumab may result in a higher levels of toxicities in patients with unresectable pleural mesothelioma than was reported in the CheckMate 743 trial, according to a recent study published by McNamee et al in the Journal of Thoracic Oncology.


Australia has one of the highest rates of asbestos-associated diseases such as mesothelioma—which remains an area of unmet need, with a 5-year overall survival rate of 10%.

Based on the results of the CheckMate 743 trial and supportive data from the later-line single-arm MAPS2 trial, first-line ipilimumab plus nivolumab may be the standard of care for the treatment of this patient population.

Study Methods and Results

In the new RIOMeso study, investigators retrospectively collected demographic and clinicopathologic data from 119 patients, with a median age of 72, who had pleural mesothelioma and received treatment with ipilimumab plus nivolumab in both first-line and subsequent settings. A total of 83% of the patients were male, 92% had Eastern Cooperative Oncology Group (ECOG) scores ≤ 1, 50% were current or former smokers, and 78% had known asbestos exposure. Additionally, 50%, 19%, and 14% of the patients had epithelioid, sarcomatoid, and biphasic mesothelioma, respectively.

The investigators further assessed the patients’ survival and toxicity outcomes using the Kaplan-Meier method and the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, respectively.  

The investigators reported the median overall survival among all patients was 14.5 months. First-line use of ipilimumab and nivolumab was observed in 75% of patients. Those treated with the drug combination in a second- or later-line setting had a median overall survival of 15.4 months.

The investigators reported no statistically significant differences in median overall survival between patients with epithelioid and nonepithelioid histology. Approximately 24% of the patients experienced CTCAE grade ≥ 3 adverse events—with colitis being the most frequent.


According to the investigators, their new findings may mark a significant milestone as one of the first detailed reports of real-world survival and toxicity outcomes in patients undergoing ipilimumab and nivolumab treatment for pleural mesothelioma. They suggested that in real-world practice, the immunotherapy combination may have poorer survival outcomes and cause more toxicities compared with clinical trial data—underscoring the significance of understanding the treatment landscape beyond controlled trial settings.

However, the investigators urged caution when interpreting the results of their recent study. “There is certainly survival benefit of the CheckMate 743 regimen over chemotherapy, especially in the nonepithelioid group; however, perhaps there is more equipoise in [patients with] epithelioid [mesothelioma]. Careful patient selection may mitigate some of the risk of toxicity, but our study demonstrates that the nonchemotherapy option is not necessarily less toxic,” concluded Ned McNamee, MMed, of the Kinghorn Cancer Centre & St. Vincent's Hospital in Australia.

Disclosure: For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.