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Prevalence of PDL1 Amplification and Preliminary Response to Immune Checkpoint Blockade in Solid Tumors

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Prevalence of PDL1 Amplification and Preliminary Response to Immune Checkpoint Blockade in Solid Tumors Supplementary Online Content Goodman AM, Piccioni D, Kato S, et al. Prevalence of PDL1 Amplification and Preliminary Response to Immune Checkpoint Blockade in Solid Tumors. JAMA Oncol. Published online June 14, 2018. doi:10.1001/jamaoncol.2018.1701 Supplement. eFigure. CONSORT Diagram eTable 1. Biomarkers for Response to Immunotherapy in 13 Patients With PD-L1 Amplification Seen at University of California, San Diego Moores Cancer Center eTable 2. Definitions for PD-L1 IHC Positivity eTable 3. PDL1 Amplification by Solid Tumor Type (PDL1 Amplification Was Seen in 0.7% of 118 187 Samples With Malignancies) eTable 4. Clinical Characteristics of 13 Patients With PDL1 and/or PDCD1LG2 (PDL2) Amplifications Seen at UCSD Center for Personalized Cancer Therapy eTable 5. Patient Profiles and treatment Response eTable 6. PDL1/L2 Alterations Other Than Amplifications eFigure 2. Patient # 4 with glioblastoma This supplementary material has been provided by the authors to give readers additional information about their work. © 2018 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 0.7% samples with 118,187 samples at Foundation PD-L1 CNAs Medicine 2,039 samples at UC San Diego Center for Personalized Cancer Therapy 13 patients identified with PD-L1 CNAs seen at UCSD 9 (69%) patients treated with 4 (31%) patients not treated with checkpoint blockade checkpoint blockade 1 (8%) patient treated with allogeneic stem cell transplantation eFigure. CONSORT Diagram Abbreviations: CNAs = copy number alterations; UC = University of California © 2018 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 eTable 1. Biomarkers for Response to Immunotherapy in 13 Patients With PD-L1 Amplification Seen at University of California, San Diego Moores Cancer Center* Patien PD-L1 PD-L1 Average TMB MSI Histology/disease t expressio expressio percentag (mutations/mb)** statu status n on n on TILs e of TILs * s tumor per high cells by power IHC* field** 1 Low Low NA 7.19 Stabl Head and neck positive1 positive e squamous cell carcinoma/ Metastatic 2 NA NA NA 5 Stabl Ovarian serous e carcinoma/ Metastatic 3 NA NA NA 13 NA Gastric adenocarcinoma/ Metastatic 4 Negative2 Negative2 NA 2 Stabl Glioblastoma/Locall e y advanced 5 NA NA 50% 4 Stabl Colon e adenocarcimoma/ Metastatic 6 NA NA 60% 9 Stabl Head and neck e squamous cell carcinoma/ Metastatic 7 High High 40% 21 Stabl Bladder urothelial positive1 positive1 e carcinoma/ Metastatic 8 High Low 40% 16 NA Grey zone positive1 positive1 lymphoma/not applicable 9 NA NA NA 90 Stabl Basal cell e carcinoma/ Metastatic 10 NA NA 10% 15 Stabl Primary mediastinal e B-cell lymphoma/not applicable 11 Negative3 NA NA 104 Stabl Basal cell e carcinoma/ Metastatic 21 12 NA NA NA 5 Stabl Head and neck © 2018 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 e squamous cell carcinoma/locally advanced 13 High NA NA 7 Stabl Non-small cell lung positive2 e cancer/ Metastatic *Where data is not available, it is due to the fact that tissue was not tested for the marker and, in some patients, there is inadequate tissue or no consent for further research use of tissue; Also see Supplementary Table 2 for definitions of IHC positivity. **Average percentage of TILs using three different high power fields (400x magnification). Salgado et al. JAMA Oncology. 2015.26 *** < 5 mutations/megabase = TMB low; 6-19 mutations/megabase = TMB intermediate; > 20 mutations/megabase = TMB high. 1Pathline-EMERGE: Antibody SP142 (Ventana). 2Foundation Medicine: Antibody SP142 (Ventana) or Dako 22C3 (pharmDx). 3CARIS: Antibody SP142 (Ventana) Abbreviations: IHC = immunohistochemistry; mb = megabase; MSI = microsatellite instability; NA = not available; PD-1 = programmed death inhibitor-1; PD-L1 = programmed death-ligand 1; TILs = tumor infiltrating lymphocytes © 2018 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 eTable 2. Definitions for PD-L1 IHC Positivity Foundation Medicine Assay: Antibody SP142 (Ventana) Result Description High positive ≥50% proportion of positive staining of at least 1+ intensity Moderate positive 25-49% proportion of positive staining of at least 1+ intensity Low positive 1-24% proportion of positive staining of at least 1+ intensity Negative <1% proportion of positive staining of at least 1+ intensity, or no staining Pathline-Emerge Assay: Antibody SP142 (Ventana) or Dako 22C3 (pharmDx) High positive 1+ or 2+ staining intensity and > 25% distribution Low positive 1+ or 2+ staining intensity in 1-24% distribution Negative No staining CARIS Assay: Antibody SP142 (Ventana) Positive ≥2+ staining intensity and ≥5% of cells staining positive Negative N2+ staining intensity of <5% of cells staining positive © 2018 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 eTable 3. PDL1 Amplification by Solid Tumor Type (PDL1 Amplification Was Seen in 0.7% of 118,187 Samples With Malignancies) Cases with PD-L1 amplification Cases without PD-L1 amplification Disease % TMB TMB TMB TMB TMB TMB TMB TMB TMB TMB mean median low intermediate high mean median low intermediate high fraction fraction fraction fraction fraction fraction All (n = 118,187) 0.713% 13.28 6.31 41.0% 43.8% 15.2% 7.44 3.60 63.7% 29.9% 6.4% lung adenocarcinoma1 0.604% 18.08 17.12 13.3% 53.3% 33.3% 9.92 6.31 43.4% 44.6% 12.0% colon adenocarcinoma2 0.183% 7.46 4.50 55.6% 38.9% 5.6% 8.03 4.50 61.1% 33.5% 5.4% breast carcinoma (nos) 2 1.901% 5.92 4.50 50.5% 48.6% 0.9% 5.48 3.60 63.3% 33.7% 3.0% breast invasive ductal 1.995% 8.00 4.50 65.2% 32.6% 2.2% 4.40 3.60 72.3% 26.4% 1.3% carcinoma2 unknown primary 0.606% 12.44 8.11 28.6% 52.4% 19.0% 6.92 3.60 62.2% 31.3% 6.5% adenocarcinoma2 pancreas ductal 0.030% 4.50 4.50 100.0% 0.0% 0.0% 2.68 1.80 89.6% 9.8% 0.6% adenocarcinoma2 lung non-small cell lung 1.063% 20.67 17.12 11.4% 45.7% 42.9% 12.06 8.11 32.5% 51.2% 16.3% carcinoma (nos) 2 brain glioblastoma2 0.344% 31.04 1.80 72.7% 9.1% 18.2% 7.40 2.70 80.8% 15.2% 4.0% lung squamous cell carcinoma 1.694% 12.88 9.01 14.0% 74.0% 12.0% 12.10 9.01 22.3% 67.0% 10.6% (scc) 2 ovary serous carcinoma2 0.616% 6.84 5.86 43.8% 56.3% 0.0% 3.46 2.70 76.3% 23.6% 0.1% prostate acinar 0.203% 2.52 2.70 100.0% 0.0% 0.0% 5.54 2.70 81.1% 15.7% 3.3% adenocarcinoma2 gastroesophageal junction 0.256% 12.79 7.21 40.0% 40.0% 20.0% 6.65 4.50 50.5% 47.4% 2.2% adenocarcinoma2 liver cholangiocarcinoma2 0.375% 5.08 5.41 28.6% 71.4% 0.0% 3.42 2.50 84.8% 13.3% 1.9% unknown primary carcinoma 1.278% 17.76 13.51 26.1% 56.5% 17.4% 10.54 4.50 52.5% 37.6% 9.9% (nos) 2 rectum adenocarcinoma (crc) 2 0.174% 9.01 9.01 33.3% 66.7% 0.0% 5.95 3.60 70.1% 27.6% 2.3% unknown primary melanoma2 0.501% 29.28 18.47 12.5% 37.5% 50.0% 26.92 12.61 28.7% 34.7% 36.6% bladder urothelial (transitional 0.814% 14.41 9.01 18.2% 54.5% 27.3% 10.10 7.21 33.6% 55.2% 11.2% cell) carcinoma2 stomach adenocarcinoma 0.604% 11.49 4.50 62.5% 25.0% 12.5% 6.14 3.60 65.5% 29.9% 4.6% (nos) 2 head and neck squamous cell 3.059% 12.10 7.21 41.0% 43.6% 15.4% 12.98 4.50 50.5% 37.7% 11.8% carcinoma (hnscc) 2 uterus endometrial 0.491% 3.30 3.15 66.7% 33.3% 0.0% 13.01 4.50 57.4% 28.2% 14.5% adenocarcinoma (nos) 2 skin melanoma2 0.092% 200.90 200.90 0.0% 0.0% 100.0% 31.23 14.41 25.5% 35.4% 39.1% lung small cell undifferentiated 1.307% 14.22 12.61 7.1% 64.3% 28.6% 11.32 9.01 21.5% 69.8% 8.7% carcinoma2 ovary epithelial carcinoma 1.331% 10.10 7.66 42.9% 50.0% 7.1% 5.64 3.60 68.3% 29.8% 1.9% © 2018 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 (nos) 2 pancreatobiliary carcinoma 0.100% 5.41 5.41 0.0% 100.0% 0.0% 3.74 2.70 80.5% 17.5% 2.0% (nos)3 pancreas carcinoma (nos) 0.106% 4.50 4.50 100.0% 0.0% 0.0% 3.32 1.80 88.5% 10.1% 1.4% ovary high grade serous 0.962% 4.50 2.70 66.7% 33.3% 0.0% 3.74 3.60 73.2% 26.6% 0.1% carcinoma3 soft tissue sarcoma (nos) 3 1.993% 8.30 2.92 66.7% 22.2% 11.1% 5.12 2.50 77.7% 18.2% 4.1% unknown primary squamous 2.030% 25.62 9.91 18.8% 43.8% 37.5% 17.12 7.21 35.6% 45.5% 18.9% cell carcinoma (scc) 3 kidney renal cell carcinoma 0.522% 3.38 2.70 75.0% 25.0% 0.0% 3.23 2.70 80.2% 19.7% 0.1% (nos) 3 unknown primary 0.133% 14.41 14.41 0.0% 100.0% 0.0% 6.55 2.70 68.0% 26.3% 5.7% undifferentiated neuroendocrine carcinoma3 liver hepatocellular carcinoma 0.434% 4.20 4.50 66.7% 33.3% 0.0% 4.45 3.60 65.3% 34.0% 0.7% (hcc) 3 soft tissue leiomyosarcoma3 0.723% 4.22 4.17 80.0% 20.0% 0.0% 3.54 2.50 77.3% 21.7% 1.0% uterus endometrial 0.169% 2.70 2.70 100.0% 0.0% 0.0% 13.34 4.50 54.7% 26.7% 18.6% adenocarcinoma endometrioid3 soft tissue liposarcoma3 1.022% 1.39 0.83 100.0% 0.0% 0.0% 2.29 1.67 89.7% 10.2% 0.2% breast invasive lobular 0.347% 55.86 55.86 0.0% 50.0% 50.0% 6.06 2.70 69.2% 24.6% 6.3% carcinoma (ilc) 3 kidney clear cell carcinoma3 0.348% 2.70 2.70 100.0% 0.0% 0.0% 3.21 2.70 82.2% 17.6% 0.2% gallbladder adenocarcinoma3 0.175% 0.90 0.90 100.0% 0.0% 0.0% 4.06 2.70 74.4% 24.4% 1.2% brain anaplastic astrocytoma3 0.204% 3.60 3.60 100.0% 0.0% 0.0% 4.06 1.80 88.7% 9.8% 1.4% uterus endometrial 0.207% 9.01 9.01 0.0% 100.0% 0.0% 5.75 2.70 76.6% 22.2% 1.2% adenocarcinoma papillary serous3 appendix adenocarcinoma3 0.217% 1.80 1.80 100.0% 0.0% 0.0% 3.66 1.80 82.4% 15.0% 2.6% uterus leiomyosarcoma3 0.655% 6.12 6.68 33.3% 66.7% 0.0% 3.49 2.50 74.5% 25.1% 0.4% brain meningioma3 0.000% 0.00 0.00 NA NA NA 2.05 1.80 93.2% 6.6% 0.2% pleura mesothelioma3
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