Discordant Response to Nivolumab Plus Ipilimumab and Identification of BRAF V600E Mutation in Biphasic Malignant Pleural Mesothelioma: Case Report

Our plain-English summary of Discordant Response to Nivolumab Plus Ipilimumab and Identification of BRAF V600E Mutation in Biphasic Malignant Pleural Mesothelioma: Case Report, by O. Wilkins, A. Omogbehin, P.J. Bergquist, et al (JTO Clinical and Research Reports, 2025).

The study

• Authors: O. Wilkins, A. Omogbehin, P.J. Bergquist, C. Kim, S.V. Liu, J.E. Reuss
• Journal: JTO Clinical and Research Reports
• Published: 2025;6(5):100820
• Type of article: Case report
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Therapeutic advancement for malignant pleural mesothelioma (MPM) has been limited. Combination immunotherapy with nivolumab plus ipilimumab is a frontline treatment option for advanced MPM that is typically deployed for patients with sarcomatoid or biphasic MPM. Here, we present a case of biphasic MPM that exhibited a unique response pattern to first-line treatment with nivolumab plus ipilimumab, with brisk response in pleural and mediastinal sites of disease, but rapid progression in osseous/soft tissue sites of disease complicated by pathologic spinal cord compression. Pathologic findings from bony metastasis at progression found pure epithelioid histology without any evidence of sarcomatoid differentiation. Next-generation sequencing of this specimen revealed a BRAF V600E mutation, and the patient was subsequently treated with dabrafenib plus trametinib, achieving ongoing clinical and imaging response in all sites of the disease, including bones. This case supports the use of next-generation sequencing profiling in MPM, particularly in circumstances in which novel discordant response patterns are observed.

© 2025 The Authors.

In plain English

This case report described one 56-year-old man with occupational asbestos exposure as a tunnel inspector for the local subway/metro system. In late 2023 he was diagnosed with biphasic malignant pleural mesothelioma, with 70% spindle cell and 30% epithelioid cell components. Scans showed advanced disease, including bone lesions. After one cycle of nivolumab plus ipilimumab, disease in the pleura and mediastinum nearly resolved. However, new bone metastases appeared, and he developed spinal cord compression at T8 and then at T3, each requiring surgery. Tissue removed from the spine showed only epithelioid mesothelioma, without sarcomatoid components. Genetic testing (next-generation sequencing) of that tissue found a BRAF V600E mutation. After palliative radiotherapy and one cycle of carboplatin plus pemetrexed, he began dabrafenib plus trametinib in February 2024. Scans through October 2024 showed improving bone disease and ongoing disease control. The authors concluded that sequencing may help guide treatment in such cases. They noted that no sequencing was done before treatment. So it is unclear whether the mutation was present from the start, which they considered more likely, or was acquired as the cancer resisted immunotherapy.

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 (single patient)
• Who was studied: One 56-year-old man with no documented past medical history, who first presented in October 2023
• Exposure: Occupational exposure to asbestos as a tunnel inspector for the local subway/metro system; fiber type not stated
• Main results:
  • The left pleural mass showed biphasic malignant pleural mesothelioma with 70% spindle cell and 30% epithelioid cell components
  • PET imaging in November 2023 confirmed advanced disease, including scattered bone lesions
  • After one cycle of nivolumab plus ipilimumab, imaging showed an acute T8 compression fracture with cord compression, along with new spinal metastases
  • CT showed numerous new bony metastases alongside near resolution of pleural nodularity, mediastinal adenopathy and pleural effusion
  • Pathology from the T8 laminectomy showed an epithelioid tumor consistent with epithelioid mesothelioma, with no sarcomatoid components seen
  • The patient developed recurrent malignant spinal cord compression at T3, requiring a second laminectomy
  • The patient received palliative radiotherapy to T4 to L2 and one cycle of carboplatin plus pemetrexed
  • Next-generation sequencing of the T8 laminectomy specimen found a pathogenic BRAF V600E mutation
  • Dabrafenib plus trametinib was started on February 19, 2024; imaging from April 20 to October 18, 2024 showed improvement in bone disease and ongoing disease control
  • The authors reported disease control on targeted therapy exceeding 35 weeks
  • The authors interpreted the pattern as the sarcomatoid sites presumably responding to immunotherapy while the epithelioid sites progressed
• The authors' conclusion: The authors concluded that the case shows a novel discordant response to immunotherapy in biphasic mesothelioma and a situation in which next-generation sequencing may be useful in choosing treatment
• Limitations the authors state:
  • No next-generation sequencing was done before treatment began
  • It is unclear whether the BRAF mutation was present from the start, which the authors consider more likely, or was acquired during immunotherapy resistance

Topics

Medical terms in this study, explained in our Lexicon: Nivolumab (Opdivo), Ipilimumab (Yervoy), BRAF V600E, Biphasic Mesothelioma, Pleural Mesothelioma, Immunotherapy, Sarcomatoid, Metastasis.

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• Sarcomatoid diffuse pleural mesothelioma in an 80-year-Old woman with long-term response to nivolumab plus ipilimumab: A case report — Y. Yoshida, H. Mizugaki, et al. (2025)
• Perioperative nivolumab or nivolumab plus ipilimumab in resectable diffuse pleural mesothelioma: a phase 2 trial and ctDNA analyses — J.E. Reuss, P.K. Lee, et al. (2025)
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