Double immune checkpoint inhibitor therapy for unresectable pleural mesothelioma rarely induces hyperprogressive disease: a case report

Our plain-English summary of Double immune checkpoint inhibitor therapy for unresectable pleural mesothelioma rarely induces hyperprogressive disease: a case report, by G. Naulleau, I. Monnet, G. Rousseau-Bussac, et al (Translational Lung Cancer Research, 2024).

The study

• Authors: G. Naulleau, I. Monnet, G. Rousseau-Bussac, F. Vinas, G. Mangiapan, L. Jabot, A. Boudjemaa, C. Chouaïd, J.B. Auliac, J.B. Assié
• Journal: Translational Lung Cancer Research
• Published: 2024;13(9):2448-2452
• Type of article: Case report
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Use of immune checkpoint inhibitors (ICIs) is associated with new response types, such as hyperprogressive disease (HPD), whose definition is still being discussed. Some authors use dynamic indexes to define HPD. However, since the Checkmate-743 study, ICIs have been a first-line therapy for pleural mesothelioma (PM), thereby making use of dynamic indexes less appropriate. The aim of this study is to describe two cases of HPD and then discuss its definitions and implications.

Case Description: Herein, we report two cases of PM HPD on first-line ICI therapy. A 67-year-old man with right unresectable epithelioid PM, without BAP1 or CDKN2A losses, high neutrophil/lymphocyte ratio and rapid-onset pulmonary and mediastinal HPD after two ICI cycles, died of respiratory failure 1 month after starting treatment. A 40-year-old woman with left unresectable epithelioid PM had HPD at first assessment after 4 ICI infusions with jugular thrombosis, liver metastases and more dismal biological parameters. There are multiple different ways to describe HPD, some not applicable to PM. Suspected mechanisms include macrophage reprogramming to M2 cells. There are no known predictive factors of HPD, and future works should focus on identifying them.

Conclusions: HPD is a mode of progression for ICI-treated PM patients. Further investigation is needed to better define and anticipate HPD in these patients.

2024 AME Publishing Company. All rights reserved.

In plain English

This case report described two patients with unresectable epithelioid pleural mesothelioma whose disease worsened rapidly soon after starting first-line nivolumab plus ipilimumab. This pattern is called hyperprogressive disease. Neither patient had professional asbestos exposure. Patient 1, a 67-year-old man described as a non-smoker, received nivolumab plus ipilimumab, then nivolumab alone, in July 2022. He was then admitted with severe breathlessness; CT showed major progression with mediastinal invasion. He died of respiratory failure 1 month after starting treatment. Patient 2, a 40-year-old woman who was a hairdresser and active smoker, received four infusions. Her first follow-up scan showed major progression with jugular thrombosis and liver metastases. She then had six cycles of carboplatin-pemetrexed, with a partial response; her disease later progressed and she died 9 months after diagnosis. The authors noted that both cases met Lo Russo et al.'s criteria for hyperprogressive disease. The title's claim of rarity reflected the authors' clinical impression; two cases cannot measure a rate. The authors concluded that hyperprogressive disease is possible in pleural mesothelioma treated this way and that a consensus definition and predictive markers are needed.

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 of two patients
• Who was studied: Two patients with unresectable epithelioid pleural mesothelioma diagnosed in 2022, treated in the Department of Pneumology, Centre Hospitalier Intercommunal de Créteil, France. One was a 67-year-old man described as a non-smoker. The other was a 40-year-old woman, a hairdresser and active smoker. The article states that neither had professional asbestos exposure.
• Exposure: First-line immune checkpoint inhibitor therapy with nivolumab plus ipilimumab, followed by nivolumab alone. Asbestos exposure was not the subject of the report; both patients were reported to have no professional asbestos exposure.
• Main results:
  • Patient 1 (67-year-old man) was admitted 5 days after his second treatment (nivolumab alone) with severe breathlessness requiring oxygen. CT showed major mesothelioma progression with mediastinal invasion, and he died of respiratory failure 2 days later.
  • Patient 1 died 1 month after starting treatment.
  • Patient 2 (40-year-old woman) received four infusions from June 14 to August 16, 2022. Her first assessment scan showed major progression with jugular thrombosis and liver metastases. Her albumin fell to 24 g/L and her hemoglobin to 8.7 g/dL.
  • Patient 2 then received six cycles of carboplatin-pemetrexed with a partial response. She later had peritoneal carcinomatosis and died 9 months after initial diagnosis.
  • Both cases met the hyperprogressive disease criteria of Lo Russo et al.
• The authors' conclusion: The authors concluded that hyperprogressive disease is possible in pleural mesothelioma patients treated with immune checkpoint inhibitors, and that a consensus definition and predictive markers are needed. They described their view that it occurs rarely as a clinical impression.

Topics

Medical terms in this study, explained in our Lexicon: checkpoint inhibitors, Unresectable Pleural Mesothelioma, First-line Therapy, Pleural Mesothelioma, Unresectable, Epithelioid, BAP1, CDKN2A.

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