Brief Report: Real-world toxicity and survival of combination immunotherapy in pleural mesothelioma – RIOMeso

Journal of Thoracic Oncology 2023 November 15 [Link]

N McNamee, C Harvey, L Gray, T Khoo, L Lingam, B Zhang, U Nindra, P Y Yip, A Pal, T Clay, S Arulananda, M Itchins, N Pavlakis, S Kao, S Bowyer, V Chin, L Warburton, I Pires da Silva, T John, B Solomon, M Alexander, A Nagrial


Background: Australia has one of the highest rates of asbestos-associated diseases. Mesothelioma remains an area of unmet need with a 5-yr overall survival (OS) of 10%. First line immunotherapy with ipilimumab and nivolumab is now a standard of care for unresectable pleural mesothelioma following the CheckMate743 (CM743) trial, with supportive data from the later line single arm MAPS2 trial. RIOMeso examines survival and toxicity of this regimen in real-world practice.

Methods: Demographic and clinicopathological data of Australian patients treated with ipilimumab and nivolumab in first and subsequent line settings for pleural mesothelioma was collected retrospectively. Survival was reported using the Kaplan-Meier method and compared between subgroups with the log rank test. Toxicity was investigator-assessed using CTCAE v5.0.

Results: 119 patients were identified from 11 centres. The median age was 72, 83% were male, 92% were ECOG ≤1, 50% were past or current smokers and 78% had known asbestos exposure. 50% were epithelioid, 19% sarcomatoid, 14% biphasic and 17% unavailable. Ipilimumab and nivolumab was used first line in 75% of patients. Median OS (mOS) was 14.5 months (95%CI 13.0-NA) for the entire cohort. For patients treated first line, mOS was 14.5 months (95%CI 12.5-NA) and in second or later line patients was 15.4 months (95%CI 11.2-NA). There was no statistically significant difference in mOS for epithelioid histology compared to non-epithelioid (19.1 months [95%CI 15.4-NA] vs 13.0 months [95%CI 9.7-NA] respectively, P=0.064). 24% of patients had a CTCAE grade ≥ 3 adverse event, including 3 treatment-related deaths. Colitis was the most frequent adverse event.

Conclusion: Combination immunotherapy in real-world practice has poorer survival outcomes and appears more toxic compared with clinical trial data. This is the first detailed report of real-world survival and toxicity outcomes using ipilimumab and nivolumab treatment of pleural mesothelioma.