Programmed Death Ligand-1 Immunohistochemistry: Friend or Foe?

Kerr, Keith M.; Hirsch, Fred R.

doi:10.5858/arpa.2015-0522-sa

Cited by 125 publications

(83 citation statements)

References 31 publications

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“…It is now understood that PD-L1 protein expression is not binary; it is a continuous variable whereby a range of PD-L1 expression levels are observed, with tumor heterogeneity also frequently noted (21,23,31), all of which may have biological and/or clinical significance. Staining cutoffs are used to classify patients with high or low/no tumor PD-L1 expression (20,23), and the cutoff appropriate for clinical decision making for each PD-1 or PD-L1 therapy is determined by clinical data.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Agreement between Programmed Cell Death Ligand-1 Diagnostic Assays across Multiple Protein Expression Cutoffs in Non–Small Cell Lung Cancer

Ratcliffe

Sharpe

Midha

et al. 2017

Clinical Cancer Research

276

219

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Purpose: Immunotherapies targeting programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) demonstrate encouraging antitumor activity and manageable tolerability in non–small cell lung cancer (NSCLC), especially in patients with high tumor PD-L1 expression, as detected by companion or complementary diagnostic assays developed for individual agents. A laboratory is unlikely to use multiple assay platforms. Furthermore, commercially available diagnostic assays are not standardized, and different assay methods could lead to inappropriate treatment selection. This study establishes the extent of concordance between three validated, commercially available PD-L1 IHC diagnostic assays for NSCLC patients [Ventana SP263 (durvalumab), Dako 22C3 (pembrolizumab), and Dako 28-8 (nivolumab)]. Experimental Design: Five hundred formalin-fixed, paraffin-embedded archival NSCLC samples were obtained from commercial sources. Stained slides were read in batches on an assay-by-assay basis by a single pathologist trained in all methods, in a Clinical Laboratory Improvements Amendments program–certified laboratory. An additional pathologist performed an independent review of 200 stained samples for each assay. Results: PD-L1 expression was evaluable with all assays in 493 samples. The three assays showed similar patterns of tumor membrane staining, with high correlation between percent PD-L1 staining. An overall percentage agreement of >90% was achieved between assays at multiple expression cutoffs, including 1%, 10%, 25%, and 50% tumor membrane staining. Conclusions: This study builds optimism that harmonization between assays may be possible, and that the three assays studied could potentially be used interchangeably to identify patients most likely to respond to anti-PD-1/PD-L1 immunotherapies, provided the appropriate clinically defined algorithm and agent are always linked. Clin Cancer Res; 23(14); 3585–91. ©2017 AACR.

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Section: Discussionmentioning

confidence: 99%

“…Staining cutoffs are used to classify patients with high or low/no tumor PD-L1 expression (20,23), and the cutoff appropriate for clinical decision making for each PD-1 or PD-L1 therapy is determined by clinical data.…”

Section: Discussionmentioning

confidence: 99%

Agreement between Programmed Cell Death Ligand-1 Diagnostic Assays across Multiple Protein Expression Cutoffs in Non–Small Cell Lung Cancer

Ratcliffe

Sharpe

Midha

et al. 2017

Clinical Cancer Research

276

219

View full text Add to dashboard Cite

show abstract

“…194 Although it is not an optimal biomarker, PD-L1 expression is currently the best available biomarker to assess whether patients are candidates for pembrolizumab. 195,196 PD-L1 expression is continuously variable and dynamic; thus, a cutoff value for a positive result is artificial. Patients with PD-L1 expression levels just below and just above 50% will probably have similar responses.…”

Section: Immunotherapeutic Agentsmentioning

confidence: 99%

Non–Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

Ettinger¹,

Wood²,

Aisner³

et al. 2017

J Natl Compr Canc Netw

1,127

1,005

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“…clone from DAKO; SP142 clone and SP263 clone from Ventana) have been developed and used successfully in clinical trials for detection of PD-L1 protein expression in different tumor types (reviewed in [11]). Although PD-L1 overexpression is associated with greater clinical response (particularly to anti-PD1 antibodies) [11], the available clinical data indicate that only 10-30% tumors with PDL1 over expression respond to the PD-1/PD-L1 checkpoint inhibitors [11][12][13][14]. The reasons for this discrepancy might be due to different drugs, different antibody clones (validated for specific platforms, e.g.…”

Section: Introductionmentioning

confidence: 99%

PD-L1 status in refractory lymphomas

et al. 2016

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Targeted immunotherapy based on PD-1/PD-L1 suppression has revolutionized the treatment of various solid tumors. A remarkable improvement has also been observed in the treatment of patients with refractory/relapsing classical Hodgkin lymphoma (cHL). We investigated PD-L1 status in a variety of treatment resistant lymphomas. Tumor samples from 78 patients with therapy resistant lymphomas were immunohistochemically (IHC) investigated for the expression of PD-L1 using two antibody clones (SP142 and SP263, Ventana). Thirteen PD-L1+ cases were further analyzed for gene copy number variations (CNV) by NGS and for PD-L1/JAK2/PD-L2 co-amplification using fluorescent in-situ hybridization assay (FISH). PD-L1 positivity (!5% positive cancer cells, IHC) was present in 32/77 (42%) and 33/71 cases (46%) using SP142 and SP263 antibodies, respectively. Concordance between the two anti-PD-L1 clones was high with only three (4%) discrepant cases. The strongest and consistent (10/11 cases) expression was observed in cHL and primary mediastinal B-cell lymphomas (3/3). Diffuse large B-cell lymphomas (DLBCL) were frequently positive (13/26) irrespective of subtype. Follicular (1/8), peripheral T-cell (3/11) and mantle cell (1/8) lymphomas were rarely positive, while small lymphocytic lymphoma/CLL and marginal zone lymphomas were consistently negative (3/3). Co-amplification/CNVs of PD-L1/ JAK2/PD-L2 were observed in 3 cases of DLBCL and cHL, respectively. Of note, all three cHL-amplified cases were positive by FISH, but not by NGS. Since only a fraction of the IHC positive lymphoma cases were positive by FISH and NGS assays, other mechanisms are involved in PD-L1 upregulation, especially in DLBCL. FISH assay may be more suitable than NGS assay for determination of PD-L1 alterations in cHL.

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Programmed Death Ligand-1 Immunohistochemistry: Friend or Foe?

Cited by 125 publications

References 31 publications

Agreement between Programmed Cell Death Ligand-1 Diagnostic Assays across Multiple Protein Expression Cutoffs in Non–Small Cell Lung Cancer

Agreement between Programmed Cell Death Ligand-1 Diagnostic Assays across Multiple Protein Expression Cutoffs in Non–Small Cell Lung Cancer

Non–Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

PD-L1 status in refractory lymphomas

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