Pseudo-hyperprogression of Malignant Pleural Mesothelioma Treated with Nivolumab

Our plain-English summary of Pseudo-hyperprogression of Malignant Pleural Mesothelioma Treated with Nivolumab, by M. Yanai, T. Sakamoto, T. Nonaka, et al (Internal Medicine, 2025).

The study

• Authors: M. Yanai, T. Sakamoto, T. Nonaka, T. Nakada, S. Matsuoka, S. Moriyama, N. Yamamoto, Y. Teruya, Y. Funaki, T. Harada, N. Kinoshita, K. Yamaguchi, M. Kodani, A. Yamasaki
• Journal: Internal Medicine
• Published: 2025;64(15):2386-2389
• Type of article: Case report
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Currently, immune checkpoint inhibitors (ICIs) are the standard treatment for malignant pleural mesothelioma (MPM). The characteristic responses to ICI treatment include pseudoprogression (PP) and hyperprogressive disease (HPD), which require attention. Reports on PP of MPM are rare. We herein report a 59-year-old woman with MPM whose pleural lesions rapidly increased in size after initiating nivolumab treatment. This was initially judged as HPD but was subsequently diagnosed as PP owing to a marked reduction in tumor size. This case highlights the importance and difficulty of differentiating between PP and true progression, including HPD, during treatment of MPM with ICIs.

In plain English

This case report from Japan described one 59-year-old woman, a never-smoking dental technician with a history of asbestos exposure, who had stage IIIB epithelial-type malignant pleural mesothelioma. Her disease progressed after two cycles of cisplatin and pemetrexed, so she was started on nivolumab, an immune checkpoint inhibitor. After three cycles, the pleural tumor filled almost the entire right chest cavity, and she had respiratory failure, swelling and very poor general condition (performance status 4). The doctors suspected hyperprogressive disease, meaning rapid tumor growth. They stopped nivolumab and gave supportive care only. Two months after the last dose, her right lung had re-expanded and the tumor had shrunk. The doctors then concluded that the earlier growth was pseudoprogression, a temporary enlargement followed by shrinkage. They restarted nivolumab, the tumor shrank further, and treatment continued for six months. A blood-count ratio proposed elsewhere as a sign of pseudoprogression did not fit this case. The authors concluded that telling pseudoprogression from true progression was difficult but essential, and that immunotherapy-specific response criteria such as iRECIST should be used.

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 (one patient)
• Who was studied: One 59-year-old woman, a non-smoker, with cT4N0M0 stage IIIB epithelial-type malignant pleural mesothelioma, referred to the authors' hospital (the authors are affiliated with Tottori University Hospital, Japan)
• Exposure: Occupational: the patient was a dental technician with a history of asbestos exposure (no fiber type or dose given). Treatment studied: nivolumab as second-line therapy after cisplatin and pemetrexed, dose printed as 240 mg/kg body weight every 2 weeks
• Main results:
  • The disease progressed after two cycles of first-line cisplatin and pemetrexed
  • After three cycles of nivolumab, CT showed the pleural lesion had grown until it occupied almost the entire right thoracic cavity; this was judged progressive disease by modified RECIST
  • Hyperprogressive disease was suspected and nivolumab was stopped; with performance status score 4, she received best supportive care only
  • Two months after the last nivolumab dose, the right lung had expanded and CT showed the pleural lesion had decreased in size
  • The authors concluded that the initial growth was pseudoprogression and resumed nivolumab
  • After nivolumab was resumed, the pleural lesion shrank further and treatment continued for six months
  • The patient's respiratory failure from a collapsed lung, edema and decreased performance status had pointed toward true progression
  • The neutrophil-lymphocyte ratio, proposed elsewhere as a marker of pseudoprogression when low, did not fit this case: pre-treatment 7.2 and post-treatment 9.1
• The authors' conclusion: The authors concluded that distinguishing pseudoprogression from hyperprogressive disease was difficult in this case. They wrote that in patients on immune checkpoint inhibitors it is essential to distinguish pseudoprogression from true progression, using response criteria such as iRECIST rather than conventional RECIST.
• Limitations the authors state:
  • Serum soluble mesothelin-related peptides, which the authors say may help tell pseudoprogression from true progression, were not measured in this case

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Nivolumab (Opdivo), checkpoint inhibitors.

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