Tumor PD-L1 expression in malignant pleural and peritoneal mesothelioma by Dako PD-L1 22C3 pharmDx and Dako PD-L1 28-8 pharmDx assays

Our plain-English summary of Tumor PD-L1 expression in malignant pleural and peritoneal mesothelioma by Dako PD-L1 22C3 pharmDx and Dako PD-L1 28-8 pharmDx assays, by D.B. Chapel, R. Stewart, L.V. Furtado, et al (Human Pathology, 2019).

The study

• Authors: D.B. Chapel, R. Stewart, L.V. Furtado, A.N. Husain, T. Krausz, G. Deftereos
• Journal: Human Pathology
• Published: 2019;87:11-17
• Cited by: 43 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma (MM) is an aggressive neoplasm with poor prognosis. The Dako PD-L1 22C3 and 28-8 pharmDx assays are approved by the US Food and Drug Administration (FDA) as companion and complementary diagnostics for the anti-PD-1 drugs pembrolizumab and nivolumab, respectively. Data from multiple clinical trials indicate that immunotherapy has antitumor activity in advanced malignant pleural (MPM) and peritoneal mesothelioma (MPeM). However, large studies of PD-L1 expression in MM using the FDA-approved anti-PD-L1 assays are lacking. We stained tissue microarray sections (N = 125; 112 MPM and 13 MPeM) using 2 FDA-approved clinical immunohistochemical makers for PD-L1 expression: Dako PD-L1 22C3 pharmDx and Dako PD-L1 28-8 pharmDx. Overall, 22% (27/125) of MMs were positive using the 22C3 assay, whereas 27% (32/117) were positive using the 28-8 assay, using a tumor proportion score cutoff of 1%. Tumor cell PD-L1 expression was strongly correlated with PD-L1 expression on tumor-associated immune cells. No significant difference in PD-L1 expression was observed by patient sex, age, treatment history, pathologic stage, or histologic subtype. However, the proportion of cases positive for PD-L1 expression was higher among MPeM compared to MPM (P = .007 for 22C3 assay; P = .04 for 28-8 assay). PD-L1 is expressed in a substantial proportion of MM cases, as measured by FDA-approved companion assays for widely used immunotherapeutic drugs. PD-L1 expression is particularly prevalent in MPeM. These findings support large clinical studies to further examine PD-L1 as a biomarker for a subset of MM patients that may benefit from immunotherapy.

Copyright © 2019 Elsevier Inc. All rights reserved.

In plain English

This laboratory study, by pathologists at the University of Chicago and the University of Utah and ARUP Laboratories, tested tumor tissue from 125 people with malignant mesothelioma: 112 pleural and 13 peritoneal cases. The authors stained the tissue with two FDA-approved tests (22C3 and 28-8) for PD-L1, tests linked to the immunotherapy drugs pembrolizumab and nivolumab. With the 22C3 test, 20 of 112 pleural cases (18%) and 7 of 13 peritoneal cases (54%) were PD-L1 positive. With the 28-8 test, 25 of 104 usable pleural cases (24%) and 7 of 13 peritoneal cases (54%) were positive. Peritoneal tumors were positive significantly more often than pleural tumors. In pleural cases, PD-L1 status was not significantly related to age, sex, recorded asbestos exposure, treatment history or stage. It was not significantly linked to survival in either group. The authors concluded that PD-L1 is present in about one-fifth to one-quarter of pleural and about half of peritoneal mesotheliomas. They noted that the number of peritoneal cases was small.

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: Laboratory pathology study measuring PD-L1 in mesothelioma tumor tissue on tissue microarrays. It used two FDA-approved assays, Dako 22C3 and 28-8 pharmDx, which are companion and complementary diagnostic tests for pembrolizumab and nivolumab.
• Who was studied: 125 malignant mesothelioma cases from the University of Chicago and University of Utah (ARUP Laboratories) pathology departments: 112 malignant pleural mesotheliomas (56 epithelioid, 48 biphasic, 10 sarcomatoid) and 13 malignant peritoneal mesotheliomas (all epithelioid). Dates of the cases are not given.
• Exposure: The main measurement was tumor PD-L1 staining. History of asbestos exposure was collected from medical records as one clinical variable; fiber types and amounts were not reported. Table 1 lists asbestos exposure in 84 of 125 cases (78 of 112 pleural, 6 of 13 peritoneal). The pleural and peritoneal groups did not differ significantly in asbestos exposure (P = .12).
• Main results:
  • With the 22C3 assay (all 125 cases usable), tumor PD-L1 was positive in 20/112 pleural cases (18%) and 7/13 peritoneal cases (54%).
  • With the 28-8 assay (117 cases usable), tumor PD-L1 was positive in 25/104 pleural cases (24%) and 7/13 peritoneal cases (54%).
  • The difference between the two assays in detecting tumor cell PD-L1 was not statistically significant, for all cases or for pleural cases only (P = .11).
  • The 28-8 assay detected PD-L1 on immune cells significantly more often than the 22C3 assay (P = .04 for all cases and for pleural cases only).
  • Tumor cell PD-L1 expression was significantly more common in peritoneal than in pleural mesothelioma (P = .007 for 22C3, P = .04 for 28-8, P = .009 for cases positive by both assays).
  • In pleural mesothelioma, tumor cell PD-L1 expression had no significant relationship with age at diagnosis, sex, asbestos exposure, treatment history, or pathologic stage.
  • Overall survival was not significantly associated with tumor cell PD-L1 expression in pleural mesothelioma (P = .73 for 28-8, P = .65 for 22C3) or in peritoneal mesothelioma (P = .80).
  • Tumor cell PD-L1 expression was strongly correlated with PD-L1 expression on tumor-associated immune cells for both assays (P less than .001).
  • With the 22C3 assay only, tumor PD-L1 expression was significantly higher in biphasic pleural mesothelioma than in epithelioid or sarcomatoid (P = .03). This was not seen with the 28-8 assay (P = .25).
  • The two assays agreed completely (100% concordance) for the 13 peritoneal cases.
• The authors' conclusion: The authors concluded that, measured by the two FDA-approved assays, tumor PD-L1 expression is present in about one-fifth to one-quarter of pleural mesotheliomas and about half of peritoneal mesotheliomas.
• Limitations the authors state:
  • The number of peritoneal mesothelioma cases was relatively low, and the authors said larger studies are warranted.
  • The use of tissue microarrays may be a shortcoming because PD-L1 expression varies within a tumor. The authors argued that four cores per tumor gave sufficient representation.
  • Three pleural patients had received chemotherapy before surgery (cisplatin plus pemetrexed), which might have changed their PD-L1 expression.

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: PD-L1, Peritoneal Mesothelioma, Malignant Mesothelioma, Neoplasm, Prognosis, Pembrolizumab (Keytruda), Nivolumab (Opdivo), Clinical Trial.

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