Pseudoprogression Associated with Clinical Deterioration and Worsening Quality of Life in Malignant Pleural Mesothelioma

Our plain-English summary of Pseudoprogression Associated with Clinical Deterioration and Worsening Quality of Life in Malignant Pleural Mesothelioma, by M.B. Barnet, R.R. Zielinski, A. Warby, et al (Journal of Thoracic Oncology, 2018).

The study

• Authors: M.B. Barnet, R.R. Zielinski, A. Warby, C.R. Lewis, S. Kao
• Journal: Journal of Thoracic Oncology
• Published: 2018;13(1):e1-e2
• Type of article: Case report
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

This letter reported two patients with malignant pleural mesothelioma (MPM), described by the authors as an aggressive asbestos-related malignancy, who responded to the immune checkpoint inhibitor pembrolizumab after pseudoprogression. Pseudoprogression is an apparent increase in tumour burden or new lesions caused by T cell infiltrate. Both patients were men with epithelioid MPM. The first, aged 65, had progressive disease after 4 cycles of carboplatin and pemetrexed. After 5 cycles of pembrolizumab, his CT scan showed progressive disease by RECIST criteria, with worsening symptoms and patient-reported outcomes (PRO). Treatment was stopped and he received best supportive care. Thirty-three weeks later his scans showed a near complete response and his PRO improved. He remained untreated 42 weeks after stopping. The second patient, aged 79, began pembrolizumab 53 months after diagnosis, following two lines of chemotherapy. Treatment was stopped after 10 cycles because of radiological progression, clinical deterioration and worsening PRO. Sixteen weeks later his scans showed a significant partial response and his PRO improved beyond baseline. He remained untreated without progression at 41 weeks. The authors stated that, to their knowledge, these were the first reported cases of pseudoprogression in MPM and that the responses could be durable. Because both patients deteriorated clinically during pseudoprogression, they questioned guidance that uses clinical status to judge immunotherapy progression. They called for research on how often pseudoprogression occurs in MPM and on biomarkers of response.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This short letter reported two cases of malignant pleural mesothelioma (MPM), epithelioid subtype, treated with the immunotherapy drug pembrolizumab. The authors described "pseudoprogression", which they defined as an increase in tumour burden and/or new lesions due to T cell infiltrate. The first patient was a 65-year-old man whose disease had progressed on chemotherapy. After 5 cycles of pembrolizumab, his CT scan showed progressive disease, and his symptoms and patient-reported quality of life worsened, so treatment was stopped. Thirty-three weeks later, with only supportive care, scans showed a near complete response. The second patient was a 79-year-old man previously given two lines of chemotherapy. He stopped pembrolizumab after 10 cycles for similar reasons. Sixteen weeks later, scans showed a significant partial response. Both men were still being observed without treatment 41 to 42 weeks after stopping. The authors stated that, to their knowledge, these were the first reported cases of pseudoprogression in MPM. They concluded that clinical status during radiological progression was not correlated with ultimate clinical benefit, and called for more research. Asbestos exposure was not described.

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 (short letter)
• Who was studied: Two men with malignant pleural mesothelioma of epithelioid subtype, aged 65 and 79. Treatment setting and dates are not stated beyond the authors' Australian (NSW) affiliations.
• Exposure: The exposure studied was treatment with the immunotherapy drug pembrolizumab. The article printed the doses as 2mg/kg every three weeks for the first patient and 200mg/m2 every three weeks for the second. Both men had earlier chemotherapy. No asbestos exposure history was reported for either patient.
• Main results:
  • The authors defined pseudoprogression as an increase in tumour burden and/or new lesions due to T cell infiltrate.
  • Patient 1: CT restaging after 5 cycles of pembrolizumab showed progressive disease by RECIST criteria, with worsening symptoms and patient-reported outcomes. Treatment was stopped.
  • Patient 1: thirty-three weeks after stopping pembrolizumab, scans showed a near complete response and patient-reported outcomes improved.
  • Patient 1 was still being observed without treatment forty-two weeks after stopping.
  • Patient 2: treatment was stopped after 10 cycles because of radiological progressive disease, clinical deterioration and worsening patient-reported outcomes.
  • Patient 2: sixteen weeks after stopping pembrolizumab, scans showed a significant partial response. Patient-reported outcomes improved beyond baseline.
  • Patient 2 was still being observed without treatment forty-one weeks after stopping.
  • The authors stated these were, to their knowledge, the first reported cases of pseudoprogression in MPM.
• The authors' conclusion: The authors concluded that these cases document pseudoprogression in MPM and show that later responses can be durable. They also concluded that clinical status during radiological progression was not correlated with ultimate clinical benefit, which raises questions about a guideline that uses clinical status in assessment.
• Limitations the authors state:
  • The authors stated that more research is needed to quantify how often pseudoprogression occurs in MPM and to identify accurate on-treatment biomarkers of response.

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: Quality of Life, Pleural Mesothelioma, checkpoint inhibitors, Pembrolizumab (Keytruda), Epithelioid, Carboplatin, Pemetrexed (Alimta), CT Scan.

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