Real-World Outcomes of Patients With Malignant Pleural Mesothelioma Receiving a Combination of Ipilimumab and Nivolumab as First- or Later-Line Treatment

Our plain-English summary of Real-World Outcomes of Patients With Malignant Pleural Mesothelioma Receiving a Combination of Ipilimumab and Nivolumab as First- or Later-Line Treatment, by S. Schmid, L. Holer, K. Gysel, et al (JTO Clinical and Research Reports, 2024).

The study

• Authors: S. Schmid, L. Holer, K. Gysel, K.L. Koster, S.I. Rothschild, L.A. Boos, L. Frehner, S. Cardoso Almeida, C. Britschgi, Y. Metaxas, M. Mark, P. Froesch, W.D. Janthur, A. Allemann, C. Waibel, C. Von der Mühll-Schill, M. Früh, L.A. Mauti
• Journal: JTO Clinical and Research Reports
• Published: 2024;5(12):100735
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objectives: On the basis of the positive results of CheckMate-743, first-line (1L) treatment of malignant pleural mesothelioma (MPM) with the combination of ipilimumab and nivolumab (ipi-nivo) has become a standard-of-care. Furthermore, patients who received 1L platinum/pemetrexed chemotherapy are often considered for second or further-line (2L+) ipi-nivo on the basis of MAPS2 results. Here we report on real-world survival and safety outcomes of ipi-nivo for patients with MPM in Switzerland.

Methods: Twelve cancer centers contributed data to this retrospective cohort. Baseline characteristics including age, sex, histology, programmed death-ligand 1 expression, Eastern Cooperative Oncology Group performance status (ECOG PS), and previous/subsequent therapies were collected. The efficacy and safety outcomes were assessed by local investigators.

Results: Of the 109 patients with MPM treated with ipi-nivo between November 2017 and March 2023 (median follow-up of 16.6 months) 75% had epithelioid, 9% biphasic, and 16% sarcomatoid histology. The median age was 72 years; 91% were males, and 83% had an ECOG PS of 0 to 1. Ipilimumab in combination with nivolumab was given as 1L in 43% and as 2L+ treatment in 57% of patients. The objective response rate was 21% in 1L and 15% in 2L+. Median progression-free survival was 6.5 and 2.8 months, respectively. Median overall survival (OS) from the start of ipi-nivo was 12.6 months for 1L and 6.9 months for 2L+. No differences in OS were observed depending on age and programmed death-ligand 1 expression. Nevertheless, the median OS was significantly worse in patients with an ECOG PS of 2 or higher than those with an ECOG PS of 0 to 1 (2.4 versus 11.9 months, p < 0.001). Treatment-related adverse events (TRAEs) of any grade related to ipi-nivo treatment occurred in 65 patients (62%). The highest-grade TRAE was 1 to 2 in 58% of these patients and 3 or higher in 42% Treatment discontinuation due to a TRAE occurred in 22% of patients.

Conclusion: In this real-world cohort of patients with MPM treated with ipi-nivo survival outcomes were inferior to those reported in the CheckMate-743 and MAPS2 trials, whereas safety outcomes were similar.

© 2024 The Authors.

In plain English

This retrospective study pooled records from 12 Swiss cancer centers on 109 patients (median age 72, 91% men) with malignant pleural mesothelioma given ipilimumab plus nivolumab between November 2017 and March 2023. Seventy-nine (86% of those with information; 17 had none) had a history of asbestos exposure. Forty-seven received the drugs as first-line systemic therapy and 62 after earlier chemotherapy. In the first-line group, 21% had an objective tumor response; median progression-free survival was 6.5 months (95% CI 3.5 to 10.6) and median overall survival 12.6 months (95% CI 6.5 to 16.5). Later-line figures were 15%, 2.8 months (95% CI 2.3 to 3.4) and 6.9 months (95% CI 4.5 to 11.6). Survival did not differ significantly by age, histology or PD-L1 expression. Median survival was 2.4 months with ECOG performance status 2 or higher (poorer everyday functioning) versus 11.9 months at 0 to 1 (p less than 0.001). Of 105 patients with safety data, 65 (62%) had treatment-related side effects; three were fatal. The authors concluded survival was inferior to the CheckMate-743 and MAPS2 trials but safety was similar.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective multicenter cohort study of patients treated in routine (real-world) care
• Who was studied: 109 patients with malignant pleural mesothelioma (MPM) treated at 12 cancer centers in Switzerland between November 2017 and March 2023, with data cut-off May 1, 2023. Median age was 72 and 91% were male. 47 patients received ipilimumab plus nivolumab as first-line systemic therapy and 62 received it second or later line. 23 patients had undergone surgery before receiving the drugs. Histology was 75% epithelioid, 9% biphasic and 16% sarcomatoid.
• Exposure: The exposure studied was treatment with ipilimumab plus nivolumab, given first-line or after prior platinum-doublet chemotherapy. A history of asbestos exposure was recorded in 79 patients (86% of those with data). Asbestos data were missing for 17 patients. Fiber types were not reported.
• Main results:
  • First-line group (47 patients): objective response rate 21% with no complete responses. Median progression-free survival was 6.5 months (95% CI: 3.5 to 10.6). Median overall survival was 12.6 months (95% CI: 6.5 to 16.5).
  • Second- or later-line group (62 patients): objective response rate 15% with no complete responses. Median progression-free survival was 2.8 months (95% CI: 2.3 to 3.4). Median overall survival from the start of later-line treatment was 6.9 months (95% CI: 4.5 to 11.6).
  • Both groups pooled: no significant differences in overall survival by age, histology or PD-L1 expression.
  • Both groups pooled: patients with ECOG performance status 0 to 1 had a median overall survival of 11.9 months, compared with 2.4 months for those with ECOG performance status 2 or higher (p less than 0.001).
  • Safety population (105 patients): treatment-related adverse events of any grade occurred in 65 (62%). The highest grade was grade 3 in 21%, grade 4 in 2% and grade 5 in 3%.
  • Safety population: three treatment-related adverse events were fatal (one colitis, two pneumonitis). Adverse events led to treatment discontinuation in 24 patients.
  • Treatment-related adverse events occurred in 15 of 17 patients with a history of atopy or allergy, compared with 49 of 87 patients without such a history.
• The authors' conclusion: The authors concluded that in this real-world cohort, survival outcomes with ipilimumab plus nivolumab were inferior to those reported in the CheckMate-743 and MAPS2 trials, while safety outcomes were similar. They also concluded that ECOG performance status of 2 or higher is a relevant poor prognostic factor with this regimen, which questions its use in this frail population.
• Limitations the authors state:
  • The retrospective design and the small number of patients limit the strength of the findings.
  • There was no centralized review of scans, mesothelioma response criteria were not used consistently at all centers, and progression was assessed by imaging at intervals chosen by the treating physicians.
  • A history of atopy or allergy was assigned by the physician without a strict prespecified definition.
  • PD-L1 expression was available for only a subset of patients and was assessed locally.
  • There was no statistical control for multiple testing.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Ipilimumab (Yervoy), Nivolumab (Opdivo), Pemetrexed (Alimta), Chemotherapy, Histology, Performance Status, Epithelioid.

Related studies

• Follow-up after first-Line nivOlumab plus ipilimumab in patients with diffuse pleuRal mesotheliomA: a real-world Dutch cohort study-FLORA — L.H. Douma, M.M. Hofman, et al. (2025)
• First-Line Nivolumab Plus Ipilimumab in Inoperable Epithelioid Malignant Pleural Mesothelioma: Real-World Experience From an Indian Tertiary Care Center — A. Shah, A. Agarwal, et al. (2026)
• Five-Year Clinical Outcomes With Nivolumab Plus Ipilimumab Versus Chemotherapy as First-Line Treatment for Unresectable Pleural Mesothelioma in CheckMate 743 — A. Scherpereel, P. Baas, et al. (2026)
• Real-world outcomes of first-line immunotherapy and subsequent systemic therapies in pleural mesothelioma: a multicenter study in China — B. Tian, B. Sun, et al. (2025)
• Cost-effectiveness of nivolumab plus ipilimumab as first-line treatment for American patients with unresectable malignant pleural mesothelioma — Z.M. Ye, Z.Q. Tang, et al. (2022)
• Cost-effectiveness analysis of nivolumab plus ipilimumab versus chemotherapy as the first-line treatment for unresectable malignant pleural mesothelioma — L. Yang, X. Cao, et al. (2022)

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