Retreatment With Nivolumab and Ipilimumab in Pleural Mesothelioma Following Disease Progression After a Durable Response: Case Series

Our plain-English summary of Retreatment With Nivolumab and Ipilimumab in Pleural Mesothelioma Following Disease Progression After a Durable Response: Case Series, by I. Smesseim, P. Baas, J.A. Burgers (JTO Clinical and Research Reports, 2025).

The study

• Authors: I. Smesseim, P. Baas, J.A. Burgers
• Journal: JTO Clinical and Research Reports
• Published: 2025;6(7):100835
• Type of article: Case report
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The CheckMate 743 trial established nivolumab and ipilimumab as the standard first-line treatment for unresectable pleural mesothelioma. However, optimal management following disease progression after a durable response to dual immunotherapy remains unclear. We report two cases of patients with pleural mesothelioma (epithelioid subtype) initially treated with nivolumab-ipilimumab, achieving prolonged disease control. Both patients experienced disease progression several years after treatment discontinuation and were subsequently retreated with nivolumab-ipilimumab on regulatory approval. In both cases, retreatment resulted in stable disease for at least 12 months. However, immune-related toxicities occurred, with one patient developing recurrent colitis and the other experiencing nephrotic syndrome, ultimately leading to treatment discontinuation. These cases suggest that retreatment with dual immunotherapy may be a viable strategy for selected patients with previous durable responses, although the risk of immune-related toxicity remains significant. Given the lack of prospective data, further research is needed to determine whether rechallenge with nivolumab-ipilimumab offers superior outcomes compared with chemotherapy or best supportive care in this setting. Rechallenging patients with pleural mesothelioma with nivolumab-ipilimumab after a durable response is feasible but associated with immune-related toxicity.

© 2025 The Authors.

In plain English

This case report described two patients with pleural mesothelioma (epithelioid subtype) treated at the Netherlands Cancer Institute. Both had first received carboplatin-pemetrexed chemotherapy and then the immunotherapy drugs nivolumab and ipilimumab in the INITIATE study. The first patient, aged 66, had a partial response, but treatment was stopped after 6 months because of grade 3 colitis (bowel inflammation). The disease then stayed stable for 5 years. The second, aged 82, had a partial response and no immunotherapy-related side effects over 2 years of treatment, and progression was found after 3 years of follow-up. Both were then given the same drugs again, and in both no further tumor growth was seen for at least 12 months. The first patient again developed grade 3 colitis after 1 year. The second stopped after 1.5 years because of grade 3 nephrotic syndrome, a kidney disorder, and later died. The article did not address asbestos exposure. The authors concluded that retreatment may be a viable option but carries a risk of immune-related toxicity, and that two cases cannot be generalized.

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: Case series (case report of two patients)
• Who was studied: Two patients with pleural mesothelioma (epithelioid subtype) at the Netherlands Cancer Institute, Amsterdam: a 66-year-old with right-sided disease (programmed death-ligand 1 unknown) and an 82-year-old (programmed death-ligand 1: 30%). Both had earlier been treated in the INITIATE study. No dates were given.
• Exposure: No asbestos or other fiber exposure was reported. The treatment studied was retreatment with nivolumab plus ipilimumab after the disease progressed following an earlier durable response to the same drugs.
• Main results:
  • Case 1 (66-year-old): after the first nivolumab-ipilimumab course, which was stopped after 6 months because of grade 3 colitis, the disease remained stable for 5 years.
  • Case 1: retreatment with the same drugs resulted in stable disease.
  • Case 1: after 1 year of retreatment, grade 3 immunotherapy-related colitis occurred again and immunotherapy was stopped. The disease stayed stable for more than a year, then progressed, and the patient was being treated with chemotherapy.
  • Case 2 (82-year-old): the first course of nivolumab-ipilimumab lasted 2 years with a partial response and no immunotherapy-related toxicity. Progression was detected after 3 years of follow-up.
  • Case 2: retreatment lasted another 1.5 years with stable disease.
  • Case 2: retreatment was stopped because of grade 3 immunotherapy-related nephrotic syndrome. The patient's condition then worsened and the patient died a few months later.
  • In both patients, no further tumor growth was observed for at least 12 months after retreatment.
• The authors' conclusion: The authors concluded that rechallenge with nivolumab-ipilimumab in pleural mesothelioma may be a viable option, though it carries a risk of immune-related toxicity, and that further research is needed to compare it with chemotherapy or best supportive care.
• Limitations the authors state:
  • Because only two patients were described, the findings cannot be generalized to a broader population.
  • The authors cannot rule out that both patients would also have responded if they had received chemotherapy instead.

Topics

Medical terms in this study, explained in our Lexicon: Nivolumab (Opdivo), Ipilimumab (Yervoy), Pleural Mesothelioma, Disease Progression, CheckMate 743, Unresectable Pleural Mesothelioma, Immunotherapy, Epithelioid.

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• Safety of First-Line Nivolumab Plus Ipilimumab in Very Old (≥ 80 Years) Patients With Unresectable Malignant Pleural Mesothelioma: A Retrospective Single-Center Case Series — T. Shimamoto, Y. Morimoto, et al. (2024)
• Haemophagocytic Lymphohistiocytosis Following Ipilimumab and Nivolumab in Malignant Pleural Mesothelioma: A Case Report — C.M. Than, M. Moe, et al. (2026)
• Major response of a peritoneal mesothelioma to nivolumab and ipilimumab: a case report, molecular analysis and review of literature — M.F. Reveneau, J. Masliah-Planchon, et al. (2024)
• Comparison of FDG-PET/CT and CT for evaluation of tumor response to nivolumab plus ipilimumab combination therapy and prognosis prediction in patients with unresectable malignant pleural mesothelioma — K. Kitajima, K. Kuribayashi, et al. (2024)
• Discordant Response to Nivolumab Plus Ipilimumab and Identification of BRAF V600E Mutation in Biphasic Malignant Pleural Mesothelioma: Case Report — O. Wilkins, A. Omogbehin, et al. (2025)
• Partial Response to Nivolumab and Ipilimumab in a Patient With Malignant Pleural Mesothelioma and Pre-Existing Myasthenia Gravis Without Severe Flares or Immune-Related Adverse Events: A Case Report — M. Higa, T. Kuda, et al. (2025)

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