Major response of a peritoneal mesothelioma to nivolumab and ipilimumab: a case report, molecular analysis and review of literature

Our plain-English summary of Major response of a peritoneal mesothelioma to nivolumab and ipilimumab: a case report, molecular analysis and review of literature, by M.F. Reveneau, J. Masliah-Planchon, M. Fernandez, et al (Frontiers in Oncology, 2024).

The study

• Authors: M.F. Reveneau, J. Masliah-Planchon, M. Fernandez, A. Ouikene, B. Dron, I. Dadamessi, C. Dayen, L. Golmard, B. Chauffert
• Journal: Frontiers in Oncology
• Published: 2024;14:1410322
• Type of article: Case report
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant peritoneal mesothelioma (MPM) is a rare tumor associated with a poor prognosis and a lack of consensus regarding treatment strategies. While the Checkmate 743 trial demonstrated the superiority of first-line nivolumab and ipilimumab over chemotherapy in malignant pleural mesothelioma (MPlM), few studies have assessed the effectiveness of immunotherapy against MPM, due to its rarity. Here, we report a major and sustained 12-month response in a 74-year-old female patient who received the anti-PD-1 nivolumab and the anti-CTLA4 ipilimumab as first-line therapy for diffuse MPM. PD-L1 was expressed and BAP1 expression was lost, as shown by immunohistochemistry, however the BAP1 gene was not mutated. Our findings suggest a role for ICI in non-resectable diffuse MPM exhibiting PD-L1 overexpression and loss of BAP1 expression, and instill new hope in their treatment. To our knowledge, this is the second reported case of dual immunotherapy used as first-line in MPM with a major clinical response. To investigate the clinical outcome, we conducted additional molecular analyses of the MPM tumor and we reviewed the literature on immunotherapy in MPM to discuss the role of PD-L1 and BAP1.

Copyright © 2024 Reveneau, Masliah-Planchon, Fernandez, Ouikene, Dron, Dadamessi, Dayen, Golmard and Chauffert.

In plain English

This article is a case report from Saint Quentin Hospital in France. It also describes molecular testing of the tumor and reviews published reports on immunotherapy for malignant peritoneal mesothelioma. The patient was a 74-year-old woman with diffuse epithelioid-type peritoneal mesothelioma that could not be completely removed by surgery. The article states she had no history of exposure to asbestos. Her tumor had lost the BAP1 protein and expressed the PD-L1 protein, with a combined positive score of 10. As her first treatment, from April 2022 to April 2023, she received 10 injections of the immunotherapy drug nivolumab every 3 weeks, together with the immunotherapy drug ipilimumab every 6 weeks. Her abdominal pain disappeared, her general condition improved, and CT scans showed less disease in the peritoneum. In May 2023 the disease grew again, and she was switched to chemotherapy with pemetrexed, carboplatin and bevacizumab. In March 2024, 24 months after diagnosis, she remained well while receiving pemetrexed and bevacizumab maintenance therapy. Gene sequencing found no changes in the BAP1 gene or in the other genes examined. The authors suggested a potential role for this treatment in similar tumors, but cautioned that response rates should not be extrapolated from this single case.

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 report with molecular analysis of the tumor and a review of the literature on immunotherapy in malignant peritoneal mesothelioma
• Who was studied: One 74-year-old woman treated at Saint Quentin Hospital, France, referred in February 2022 and diagnosed with diffuse epithelioid-type malignant peritoneal mesothelioma that could not be completely resected
• Exposure: No asbestos exposure was reported for this patient. The treatment studied was 10 injections of nivolumab, 360 mg every 3 weeks, given with ipilimumab, 1 mg/kg every 6 weeks, from April 2022 to April 2023
• Main results:
  • Immunohistochemistry of the patient's tumor showed loss of BAP1 protein expression and expression of PD-L1, with a combined positive score of 10. Tumor mutational burden was low.
  • During nivolumab and ipilimumab treatment the patient's abdominal pain disappeared and her performance status improved. CT scans showed reduced peritoneal infiltration.
  • In May 2023 the patient had renewed pain, and CT showed new nodules in the peritoneum and right pleura. Immunotherapy was stopped.
  • Subsequent chemotherapy with pemetrexed, carboplatin and bevacizumab led to a sustained major response. In March 2024, 24 months after diagnosis, the patient remained well while on pemetrexed and bevacizumab maintenance therapy.
  • Gene sequencing of the patient's tumor found no alterations in the BAP1 gene despite the loss of the protein. No mutations were found in the other tumor suppressor genes and oncogenes examined.
• The authors' conclusion: The authors concluded that the case suggests a potential role for immune checkpoint inhibitors in non-resectable diffuse peritoneal mesothelioma with PD-L1 overexpression and loss of BAP1 expression. They also called for cautious interpretation.
• Limitations the authors state:
  • Response rates should not be extrapolated from a single case report, and the authors cite publication bias in this field
  • The gene panel may not have detected structural changes in BAP1 regulatory regions, such as promoter deletions
  • EZH2 protein levels were not analyzed; only EZH2 mutations were tested

Topics

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma, Nivolumab (Opdivo), Ipilimumab (Yervoy), Prognosis, CheckMate 743, Chemotherapy, Pleural Mesothelioma, Immunotherapy.

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• 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)
• Retreatment With Nivolumab and Ipilimumab in Pleural Mesothelioma Following Disease Progression After a Durable Response: Case Series — I. Smesseim, P. Baas, et al. (2025)
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