Early severe immune-related pneumonitis, hepatitis, and agranulocytosis with radiographic response in sarcomatoid malignant pleural mesothelioma treated with nivolumab and ipilimumab: a case report highlighting dual liver biopsies and rechallenge decision-making

Our plain-English summary of Early severe immune-related pneumonitis, hepatitis, and agranulocytosis with radiographic response in sarcomatoid malignant pleural mesothelioma treated with nivolumab and ipilimumab: a case report highlighting dual liver biopsies and rechallenge decision-making, by T. Oba, K. Itogawa, Y. Machida, et al (Therapeutic Advances in Medical Oncology, 2025).

The study

• Authors: T. Oba, K. Itogawa, Y. Machida, Y. Ono, Y. Morita, D. Nakatani, K. Akasaka, A. Adachi, H. Matsushima
• Journal: Therapeutic Advances in Medical Oncology
• Published: 2025;17:17588359251397331
• Type of article: Case report
• Read it: PubMed · Publisher · Free full text

Abstract

Sarcomatoid malignant pleural mesothelioma (MPM) is a rare and aggressive cancer with limited therapeutic options. We describe an exceptionally rare case of sarcomatoid MPM in a man in his 50s who developed three severe immune-related adverse events (irAEs)-Grade 3 pneumonitis, Grade 3 hepatitis, and Grade 4 agranulocytosis-within 55 days of initiating nivolumab plus ipilimumab. Corticosteroid treatment and granulocyte colony-stimulating factor resulted in recovery from these toxicities, while two liver biopsies provided essential diagnostic insights, distinguishing drug-induced liver injury from immune-related hepatitis. Despite receiving only a limited number of immune checkpoint inhibitor doses and discontinuing therapy, the patient exhibited rapid pleural tumor regression and sustained clinical benefit. This case highlights the potential association between severe immune-related side effects and favorable treatment response in MPM, and underscores the importance of pathology-supported diagnosis and shared decision-making in managing complex irAEs.

© The Author(s), 2025.

In plain English

This case report described a 59-year-old man with sarcomatoid malignant pleural mesothelioma. He was a former smoker who had worked as an electrician and had lived near an asbestos-related factory in childhood. The article gave no fiber type or exposure measurements. He began nivolumab plus ipilimumab on April 8, 2025 (Day 0). On Day 8 he developed grade 3 immune-related pneumonitis, which was treated with corticosteroids. After a second dose, of nivolumab alone, on Day 38, he developed grade 3 immune-related hepatitis. His liver enzymes peaked at AST 295 and ALT 511 U/L. A liver biopsy at that time showed features the authors called typical of immune-related hepatitis. An earlier biopsy had shown tumor plus drug-induced injury. On Day 46 he developed grade 4 agranulocytosis (neutrophil count 5/μL), which recovered with G-CSF and higher-dose steroids. A scan on Day 73 showed marked tumor shrinkage and resolution of the pleural effusion. As of August 2025 he was alive with immunotherapy suspended. The authors stated that causality cannot be confirmed from a single case and called for larger studies.

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 59-year-old man, a former smoker, with sarcomatoid malignant pleural mesothelioma, diagnosed and treated in 2024–2025
• Exposure: Asbestos history: worked as an electrician and lived near an asbestos-related factory in childhood (no fiber type or dose given). Treatment studied: nivolumab (360 mg) plus ipilimumab (1 mg/kg), followed by a second dose of nivolumab alone
• Main results:
  • On Day 8 after starting treatment, the patient developed grade 3 immune-related pneumonitis
  • After nivolumab alone was given as the second dose on Day 38, liver enzymes rose on Day 45 (AST 208, ALT 326 U/L) and peaked the next day at AST 295 and ALT 511 U/L. This was grade 3 immune-related hepatitis, and viral, autoimmune and drug-induced causes were excluded
  • The second liver biopsy showed interface hepatitis with CD3+ and CD8+ T-cell infiltration, which the authors described as typical of immune-related hepatitis
  • The first liver biopsy, taken before immunotherapy after liver injury during anti-tuberculosis treatment, showed both tumor cell infiltration and acute drug-induced hepatitis
  • On Day 46 the patient developed grade 4 agranulocytosis, with a neutrophil count of 5/μL. It recovered with 7-day G-CSF and methylprednisolone 110 mg/day
  • A CT scan on Day 73 showed marked tumor shrinkage, re-expansion of the left lung and resolution of the pleural effusion
  • As of August 2025 the patient was alive, with his general condition maintained, and immunotherapy was suspended
• The authors' conclusion: The authors concluded that the case raises the possibility that severe immune-related side effects may predict treatment benefit in malignant pleural mesothelioma. They said this is hypothesis-generating and needs study in larger groups of patients.
• Limitations the authors state:
  • A single case cannot confirm causality or be generalized
  • Follow-up was too short to draw conclusions about how long the response lasts
  • No bone marrow examination was done, so acute blood disorders such as leukemia could not be ruled out
  • The liver biopsies showed both tumor infiltration and immune-related changes, making it hard to attribute the damage
  • No biomarker analyses (driver mutations, PD-L1 expression, tumor mutational burden) were performed
  • The patient's recovery had more than one possible cause (G-CSF plus corticosteroids)
  • Restarting immunotherapy after grade 3 pneumonitis went against international guidelines and cannot be generalized

Topics

Medical terms in this study, explained in our Lexicon: Pneumonitis, Sarcomatoid, Pleural Mesothelioma, Nivolumab (Opdivo), Ipilimumab (Yervoy), Immune-Related Adverse Events, checkpoint inhibitors, Pathology.

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• Case Report: IL-6 suppression: a potential strategy for mitigating severe immune-related adverse events in nivolumab and ipilimumab therapy for malignant pleural mesothelioma — A. Yanagisawa, T. Fukaya, et al. (2025)
• Nephrotic Syndrome During Ipilimumab Plus Nivolumab Therapy for Sarcomatoid Malignant Pleural Mesothelioma: A Case Report of Nivolumab Rechallenge Without Recurrence of Nephrotic Syndrome — K. Shimaya, J. Ota, et al. (2026)
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