Precision medicine at its best: Prolonged survival in a child presenting a secondary mesothelioma treated with crizotinib

Our plain-English summary of Precision medicine at its best: Prolonged survival in a child presenting a secondary mesothelioma treated with crizotinib, by A. Petit, S. Lantuejoul, A. Mc Leer, et al (Pediatric Blood & Cancer, 2021).

The study

• Authors: A. Petit, S. Lantuejoul, A. Mc Leer, J. Mondet, C. Piolat, C. Durand, D. Moro-Sibilot, B. Geoerger, G. Vassal, H. Sartelet, D. Plantaz
• Journal: Pediatric Blood & Cancer
• Published: 2021;68(2):e28666
• Type of article: Case report, Letter
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

In plain English

This letter to the editor described one 13-year-old girl in France with malignant pleural mesothelioma. Seven years earlier she had received chemotherapy, total body irradiation and a bone marrow transplant for acute lymphoblastic leukemia. The article does not mention asbestos. Biopsies showed grade I epithelioid mesothelioma. Pemetrexed and cisplatin gave a good partial response, but tumor cells remained. Tests found an ALK gene rearrangement in 25% of tumor cells, without ALK protein on staining, and strong c-MET protein in 100% of tumor cells, without MET gene amplification. RNA sequencing meant to confirm the ALK rearrangement and/or c-MET amplification failed because too few cancer cells were present. Crizotinib, which targets ALK and c-MET, gave a very good partial response lasting 3 years. It was stopped because of digestive side effects. The cancer returned 15 days later and responded again when crizotinib was restarted. Eight months later it relapsed during treatment. Pembrolizumab in a clinical trial produced a partial response; she received it for 2 years. The authors concluded that molecular analysis found treatment targets allowing prolonged survival in this case.

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 (letter to the editor) describing one patient
• Who was studied: One 13-year-old girl treated at the university hospital in Grenoble, France (author affiliations); dates of care not given
• Exposure: No asbestos exposure is mentioned. The mesothelioma, called 'secondary' in the title, followed treatment 7 years earlier for acute lymphoblastic leukemia. That treatment was chemotherapy and allogeneic bone marrow transplantation with a conditioning regimen that included total body irradiation. The treatments studied were pemetrexed plus cisplatin, crizotinib and pembrolizumab.
• Main results:
  • The tumor was diagnosed as grade I malignant pleural mesothelioma of epithelioid subtype, with loss of BAP1 expression. The Mesopath network experts confirmed the diagnosis.
  • After four courses of pemetrexed and cisplatin, imaging showed a good partial response. Biopsies of the remaining tumor still showed tumor cells.
  • FISH showed an ALK rearrangement in 25% of tumor cells. ALK protein expression was not shown by immunohistochemistry.
  • c-MET protein was overexpressed in 100% of tumor cells at 3+ intensity. FISH showed no MET gene amplification.
  • Crizotinib produced a prolonged, very good partial response lasting 3 years. It was then stopped because of gastro-intestinal side effects.
  • Symptoms and radiological relapse returned 15 days after crizotinib was stopped. Restarting crizotinib was immediately effective.
  • A second relapse occurred eight months later while she was on crizotinib.
  • The PD-L1 tumor proportion score on the initial sample was 1%. Pembrolizumab, given in a clinical trial (NCT02332668), produced a radiological partial response, and she was treated for 2 years.
• The authors' conclusion: The authors concluded that in this case molecular analysis highlighted targets for a specific treatment that allowed prolonged survival. They also concluded that exceptionally rare pediatric tumors such as childhood pleural mesothelioma warrant thorough molecular analysis to give access to innovative drugs.
• Limitations the authors state:
  • Targeted RNA sequencing tests meant to confirm the ALK rearrangement and/or c-MET amplification failed because of the low number of malignant cells.

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: Mesothelioma.

Related studies

• Treatment status and safety of crizotinib in 2028 Japanese patients with ALK-positive NSCLC in clinical settings — N. Ueno, S. Banno, et al. (2019)
• Case report: targeted therapy of malignant pleural mesothelioma with anaplastic lymphoma kinase receptor tyrosine kinase gene fusion mutation by crizotinib — Y. Wu, Y. Zhao, et al. (2024)
• Prolonged Progression-Free Survival in a Patient With Malignant Pleural Mesothelioma Following Korean Herbal Medicine Treatment Alone: A Case Report — S.S. Yoon, E.H. Kim, et al. (2020)
• Low ERCC1 expression in malignant pleural mesotheliomas treated with cisplatin and vinorelbine predicts prolonged progression-free survival — Z.G. Zimling, J.B. Sørensen, et al. (2012)
• Immunotherapy strategies for mesothelioma - the role of tumor specific neoantigens in a new era of precision medicine — L. Ye, S. Ma, et al. (2019)
• Yale Cancer Center Precision Medicine Tumor Board: molecular findings alter a diagnosis and treatment plan — J.A. Gibson, K.E. Finberg, et al. (2021)

Browse more research in Pediatric Blood & Cancer, or return to medical research.