Complete clinical remission of malignant peritoneal mesothelioma with systemic pemetrexed and bevacizumab in a patient with a BAP1 mutation

Our plain-English summary of Complete clinical remission of malignant peritoneal mesothelioma with systemic pemetrexed and bevacizumab in a patient with a BAP1 mutation, by J. Lee, J. Turetsky, E. Nasri, et al (BMJ Case Reports, 2023).

The study

• Authors: J. Lee, J. Turetsky, E. Nasri, S.C. Rogers
• Journal: BMJ Case Reports
• Published: 2023;16(12)
• Type of article: Case report
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant peritoneal mesothelioma (MPeM) is a rare malignancy with historically poor prognosis. Recent research has started to reveal increasingly prevalent genetic mutations seen in this malignancy. Here, we report a case of complete clinical remission of unresectable, metastatic MPeM with systemic chemotherapy. Immunohistochemistry of our patient's malignant cytology sample showed loss of Breast Cancer Gene 1-associated protein-1 expression (BAP1). The patient had synchronous diagnoses of primary squamous cell carcinoma of the anus, benign schwannoma and meningioma. Following the completion of 18 cycles of pemetrexed and bevacizumab, the patient has remained in clinical remission for 8 months. We examine the unusual susceptibility of unresectable MPeM to systemic chemotherapy and attribute susceptibility to the molecular milieu created by mutations in multiple DNA repair pathways. We encourage increased testing for and analysis of mutations in DNA repair pathways to improve future treatment outcomes in this rare malignancy.

© BMJ Publishing Group Limited 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

In plain English

This case report described a woman in her 60s with malignant peritoneal mesothelioma, a cancer of the abdominal lining. The article reported no known asbestos exposure. She also had anal squamous cell carcinoma, a recurrent meningioma and a benign schwannoma. The mesothelioma was found incidentally in her right abdominal wall and later spread, causing fluid around the heart. Tests on that fluid showed loss of the BAP1 protein and a likely disease-causing BAP1 gene variant. Whether the variant was inherited is unknown because germline testing was not completed. Surgery was not an option, and platinum drugs were withheld because of her tinnitus and leg nerve damage. Over 13 months she received 18 cycles of pemetrexed and bevacizumab. Afterwards, a PET/CT scan showed no evidence of disease. Eight months into a treatment break, scans showed no definitive evidence of progression. The authors suggested the response was likely linked to other genetic changes in addition to BAP1 loss, and called for more systematic testing for DNA repair mutations. The report describes one patient and cannot show how often such responses occur.

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
• Who was studied: One woman in her 60s with unresectable, metastatic malignant peritoneal mesothelioma, who also had anal squamous cell carcinoma, recurrent meningioma and a benign schwannoma; the authors are at the University of Florida, USA
• Exposure: No known asbestos exposure was reported. The treatment studied was systemic pemetrexed 500 mg/m2 with bevacizumab 15 mg/kg every 3 weeks, 18 cycles over 13 months.
• Main results:
  • Biopsy of an incidental lesion in the right lateral abdominal wall showed peritoneal mesothelioma involving skeletal muscle and fibroadipose tissue
  • A large pericardial effusion appeared 5 months later. Its cytology matched the mesothelioma, and testing showed loss of BAP1 with a likely pathogenic BAP1 variant.
  • After 18 cycles of pemetrexed and bevacizumab, PET/CT showed no evidence of disease and the patient had no symptoms
  • The patient had been off treatment for 8 months at the time of the report, with serial PET/CTs showing no definitive evidence of progression
  • Her performance status (ECOG) was 2 at first visit and 0 after completing treatment
• The authors' conclusion: The authors concluded that the remission can likely be attributed to other genetic alterations in addition to loss of BAP1 expression, perhaps in BRCA1 or other DNA repair pathways. They recommended increased, systematic testing of patients with peritoneal mesothelioma for germline and somatic DNA repair mutations.
• Limitations the authors state:
  • It is unknown whether the patient had an inherited (germline) BAP1 mutation
  • Germline genetic sequencing was ordered but not completed by the patient
  • All imaging methods have limitations in detecting peritoneal lesions

Topics

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

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma, Pemetrexed (Alimta), Bevacizumab, BAP1, Prognosis, Unresectable, Chemotherapy, Immunohistochemistry.

Related studies

• BAP1 Is Altered by Copy Number Loss, Mutation, and/or Loss of Protein Expression in More Than 70% of Malignant Peritoneal Mesotheliomas — N. Leblay, F. Leprêtre, et al. (2017)
• BAP1 mutation is a frequent somatic event in peritoneal malignant mesothelioma — H. Alakus, S.E. Yost, et al. (2015)
• Complete pathological response to neoadjuvant pemetrexed/cisplatin in combination with regional hyperthermia in a patient with sarcomatoid peritoneal mesothelioma — S. Kruger, M.K. Angele, et al. (2014)
• Systemic chemotherapy with pemetrexed and cisplatin for malignant peritoneal mesothelioma: a single institution experience — G. Lainakis, F. Zagouri, et al. (2011)
• Detecting germline BAP1 mutations in patients with peritoneal mesothelioma: benefits to patient and family members — M. Kittaneh, C. Berkelhammer (2018)
• A Tumor-Specific Neo-Antigen Caused by a Frameshift Mutation in BAP1 Is a Potential Personalized Biomarker in Malignant Peritoneal Mesothelioma — J. Lai, Z. Zhou, et al. (2016)

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