Case report: targeted therapy of malignant pleural mesothelioma with anaplastic lymphoma kinase receptor tyrosine kinase gene fusion mutation by crizotinib

Our plain-English summary of Case report: targeted therapy of malignant pleural mesothelioma with anaplastic lymphoma kinase receptor tyrosine kinase gene fusion mutation by crizotinib, by Y. Wu, Y. Zhao, L. Yu, et al (The Journal of International Medical Research, 2024).

The study

• Authors: Y. Wu, Y. Zhao, L. Yu, R. Wang, W. Feng, Y. Wu, L. Wang, H. Chen, Z. He, Q. Wang
• Journal: The Journal of International Medical Research
• Published: 2024;52(11):3000605241287320
• Type of article: Case report
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma is a rare highly invasive tumour originating from the mesothelial cells of the pleura, peritoneum and pericardium. Malignant pleural mesothelioma (MPM) is the most common type in all malignant mesothelioma. The onset of MPM is associated with exposure to asbestos and it can have an incubation period of up to 40 years. The incidence of MPM has been increasing worldwide in recent years, so more attention has been focused on its diagnosis, treatment and prognosis. Activating mutations, amplifications and fusions/rearrangements of the anaplastic lymphoma kinase receptor tyrosine kinase (ALK) gene are commonly seen in patients with non-small cell lung cancer. However, it is rare in MPM. This current case report describes a female patient with advanced MPM with an ALK gene fusion mutation. In this particular case, treatment with crizotinib demonstrated some initial efficacy, which suggests that this might be a promising strategy for patients with advanced MPM with an ALK gene mutation. This required further research and evaluation in the future.

In plain English

This was a case report of one patient treated at a cancer hospital in Zhengzhou, Henan Province, China. The patient, a woman in her early 70s admitted in March 2022 with a lung mass and pleural nodules, had no history of smoking, family history of disease, or asbestos exposure. Biopsy and laboratory tests, including one showing CDKN2A gene deletion, led to a diagnosis of stage IV malignant pleural mesothelioma rather than lung adenocarcinoma. Gene sequencing found an EML4-ALK gene fusion. The patient took the drug crizotinib, 250 mg by mouth twice a day, for 150 days. Side effects were mild skin itching, nausea and vomiting, which the authors called tolerable. After 3 months, scans showed the lung mass and pleural thickening had become smaller, chest tightness and abdominal distension eased, and the response was rated a partial response. After 5 months, the mass and pleural thickening had grown slightly, but the authors rated this a maintained partial response. The authors reported progression-free survival of 5 months. They concluded that crizotinib is a potential new option for patients with this mutation, noting that only one case was reported and more cases 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 (single patient)
• Who was studied: One woman in her early 70s, admitted in March 2022 to The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan Province, China, with a lung mass and pleural nodules
• Exposure: The patient had no history of asbestos exposure, smoking or family history of disease. The treatment studied was crizotinib, 250 mg orally twice a day for 150 days.
• Main results:
  • In the patient's biopsy specimen, FISH staining was positive for deletion of the CDKN2A gene. The authors took this as confirming malignant pleural mesothelioma rather than lung adenocarcinoma.
  • Next generation sequencing of 26 lung cancer-related genes found an EML4-ALK subtype 3 (E6a: A20) gene rearrangement. The patient was diagnosed with advanced MPM with an EML4-ALK fusion, T4N2M1, stage IV.
  • During crizotinib treatment, the patient had mild skin itching and nausea and vomiting, which were tolerable.
  • After 3 months of crizotinib, CT showed the left lower lobe mass and left pleural thickening with nodules were smaller.
  • After 3 months, the patient's chest tightness and abdominal distension were alleviated, and the response was evaluated as a partial response (PR).
  • After 5 months of crizotinib, CT showed the lung mass and pleural nodule had increased slightly, with pleural effusion. The response was evaluated as PR maintenance.
  • The authors reported the patient's progression-free survival as 5 months.
• The authors' conclusion: The authors concluded that this case indicates crizotinib is a potential new option for patients with MPM with an ALK mutation, and that further studies of its effectiveness and safety are needed.
• Limitations the authors state:
  • Only one case was reported. More cases are needed to verify the efficacy and mechanism of crizotinib in MPM with an ALK gene mutation.

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: Targeted Therapy, Pleural Mesothelioma, Malignant Mesothelioma, Mesothelial Cells, Pleura, Peritoneum, Pericardium, Prognosis.

Related studies

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• Coactivation of receptor tyrosine kinases in malignant mesothelioma as a rationale for combination targeted therapy — M. Brevet, S. Shimizu, et al. (2011)
• Acquired multiple mutations ALK I1171N, L1196M and G1202R mediate lorlatinib resistance in EML4-ALK-rearranged malignant pleural mesothelioma: a case report — J. Hu, B. Zhang, et al. (2020)
• Treatment status and safety of crizotinib in 2028 Japanese patients with ALK-positive NSCLC in clinical settings — N. Ueno, S. Banno, et al. (2019)
• Patients with peritoneal mesothelioma lack epidermal growth factor receptor tyrosine kinase mutations that would make them sensitive to tyrosine kinase inhibitors — N. Kalra, A. Ashai, et al. (2012)
• FISH Analysis of Crizotinib Target Genes ROS1/ALK/MET in Malignant Mesothelioma — S. Salvi, S. Varesano, et al. (2017)

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