Dal PDL-1 al Tumor Mutational Burden: Fattori predittivi di risposta ai farmaci immunoterapici - Aiom
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Fattori predittivi di risposta ai farmaci immunoterapici
dal PDL-1 al Tumor Mutational Burden:
l’anatomo-patologo
Giancarlo Troncone
Elena Vigliar
PD-L1 detection with immunohistochemistry (IHC) is the only predictive
biomarker available to date for PD-L1/PD1 immunotherapy
IASLC ATLAS OF PD-L1 IMMUNOHISTOCHEMISTRY TESTING IN LUNG CANCER
ISBN: 978-0-9832958-7-7 Copyright c 2017 International Association for the Study of Lung Cancer
Pre-analytical phase issues
• use of a 10% formalin buffer
• the duration of fixation
• storage of unstained slides
• storage of tissue blocks under controlled conditions (temperature,
humidity, light)
Pre-analytical phase issues
• use of a 10% formalin buffer
• the duration of fixation
• storage of unstained slides
• storage of tissue blocks under controlled conditions (temperature,
humidity, light)
Analytical phase issues
>50% >10%
>5%
>11%
Triple negative
brest cancer Urothelial
carcinoma
>1% TC-IC >5%
IC
>50% >10%
>5%
>11%
Triple negative
brest cancer Urothelial
carcinoma
>1% TC-IC >5%
IC
>50% >10%
>5%
>11%
Triple negative
brest cancer Urothelial
carcinoma
>1% TC-IC >5%
ICPlatinum ineligible
>50% >10%
>5%
>11%
Triple negative
brest cancer Urothelial
carcinoma
>1% TC-IC >5%
IC>50% >10%
>5%
>11%
Triple negative
brest cancer Urothelial
carcinoma
>1% TC-IC >5%
IC>50% >10%
>5%
>11%
Triple negative
brest cancer Urothelial
carcinoma
>1% TC-IC >5%
ICNOTA SIAPEC- AIOM in merito alla
valutazione immunoistochimica di PD-L1.
Si ritiene opportuno raccomandare
l’uso di kit commerciali chiusi,
clinicamente validati (quali il Dako
PharmDx 22C3 o il Roche Ventana
SP263). Uno studio italiano recente
ha dimostrato infatti la sostanziale
riproducibilità delle valutazioni
eseguite con questi assay che
possono essere considerati
totalmente sovrapponibiliSampling issues
Small tissue sample
(biopsy, CYTOLOGY) Diagnosis of
70%
Resection of lung cancer
specimentRole of modern pathologist Jain D et al. Rapid On-Site Evaluation of Endobronchial Ultrasound-Guided Transbronchial Needle Aspirations for the Diagnosis of Lung Cancer: A Perspective From Members of the Pulmonary Pathology Society. Arch Pathol Lab Med. 2018 Feb;142(2):253-262.
Heymann JJ et al.PD-L1 expression in non-small cell lung carcinoma: comparison among cytology, small biopsy, and
surgical resection specimens. Cancer Cytopathol. 2017 Dec;125(12):896-907.
Ilie M et al. Use of the 22C3 anti-programmed death-ligand
1 antibody to determine programmed death-ligand 1
expression in cytology samples obtained from non-small
cell lung cancer patients. Cancer Cytopathol. 2018
Apr;126(4):264-274.
Torous VF, Rangachari D, Gallant BP, Shea M, Costa DB, VanderLaan PA. PD-L1 testing using the clone 22C3 pharmDx kit for selection of patients with non-small cell lung cancer to receive
immune checkpoint inhibitor therapy: are cytology cell blocks a viable option? J Am Soc Cytopathol. 2018 May-Jun;7(3):133-141.81 samples
21 resections
20 core needle or bronchial
biopsy samples
18 tumor-positive lymph node
excision biopsy
22 cytological cell blocks
24 experienced pulmonary pathologists IASLC Pathology Committee members
15 countries across five continentsPitfalls of interpreting PD-L1 expression on cytology direct smears (A) High amounts of nonspecific cytoplasmic staining (B) Nonspecific background staining of mucus (C) Cellular debris and non-tumor cells can lead to overinterpretation of the PD-L1 TPS
…dal PDL-1 al Tumor Mutational Burden
Adapted from Büttner R, et al. Implementing TMB measurement in clinical practice: considerations on assay requirements. ESMO Open. 2019 Jan 24;4(1):e000442.
PFS in Patients With High TMB (≥10 mut/Mb) by Tumor PD-L1 Expression Ready N, et al. First-Line Nivolumab Plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer (CheckMate 568): Outcomes by Programmed Death Ligand 1 and Tumor Mutational Burden as Biomarkers. J Clin Oncol. 2019:JCO1801042.
Hellmann MD, et al. Genomic Features of Response to Combination Immunotherapy in Patients with Advanced Non-Small-Cell Lung Cancer. Cancer Cell. 2018. pii: S1535-610830123-5 Rizvi H et al. Molecular Determinants of Response to Anti-Programmed Cell Death (PD)-1 and Anti-Programmed Death-Ligand 1 (PD-L1) Blockade in Patients With Non-Small-Cell Lung Cancer Profiled With Targeted Next-Generation Sequencing. J Clin Oncol. 2018;36:633-641
Büttner R, et al. Implementing TMB measurement in clinical practice: considerations on assay requirements. ESMO Open. 2019 Jan 24;4(1):e000442.
Ready N, et al. First-Line Nivolumab Plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer (CheckMate 568): Outcomes by Programmed Death Ligand 1 and Tumor Mutational Burden as Biomarkers. J Clin Oncol. 2019:JCO1801042.
Supplement to: Hellmann MD, Ciuleanu T-E, Pluzanski A, et al. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med. DOI: 10.1056/NEJMoa1801946
Anno XXIV, N. 3, marzo 2019
ISBN 978-88-6756-467-5
TMB NGS BASED
APPROACH
+
IHCProf. Giancarlo Troncone
Dr. Claudio Bellevicine Dr. Ilaria Migliatico
Dr. Eduardo Clery Dr. Mariantonia Nacchio
Dr. Floriana Conticelli Dr. Francesco Pepe
Dr. Caterina De Luca Dr. Pasquale Pisapia
Dr. Filippo De Rosa Dr. Maria Russo
Dr. Gianluca Gragnano Dr. Veronica Russo
Dr. Antonino Iaccarino Dr. Roberta Sgariglia
Dr. Umberto Malapelle Dr. Riccardo Smeraglio
elena.vigliar@unina.itYou can also read
