ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 OFP-06-003 Some aspects of lung fibrosis in COVID-19 V. Zinserling*, N. Semenova, D. Baram *V.A. Almazov Research Center, Russia Background & objectives: Lung fibrosis is considered as one of the most significant lesions in late stages of acute COVID-19 infection and post Covid syndrome. Many questions related to its pathogenesis and sequels remain unclear. Methods: We studied lungs in 16 lethal cases with known geno- type of SARSCOVi2, nearby routine methods the slices were stained according Mallory, IHC included sera against macrophages CD68+, CD163+ and collagens of 1 and 3 types. In 14 cases the slices, stained for CD68+ cells were scanned and then counted with the help of morphometric program and related to square. Results: We found that fibrosis was practically equally expressed in all cases nevertheless exact duration of the disease, which was difficult to evaluate in several cases. Genotype of the virus. Collagen was of both types 1 and 3, with the prevalence of the latter. The number of CD68+ macrophages varied from 27 till 93/ mm2. Notable that both, collagen 1 and 3 were detected not only typical fibres but also in cytoplasm of macrophages. In these regions accumulation of CD163+ macrophages was noted. In one case cirrhotic changes of the lung developed in previously healthy man in less than a year after first disease (finished clinical recovery) during the second episode. Conclusion: Thus, many issues of lung fibrosis of clinical impor- tance have to be additionally studied. OFP-06-004 Evaluation of acquired resistance to sotorasib in patients with KRAS p.G12C-mutated non-small cell lung cancer: biomarker analysis using plasma from the CodeBreaK 100 trial A. Addeo*, J. Wolf, B.T. Li, V. Velcheti, G.K. Dy, S.S. Ramal- ingam, A. Hindoyan, A. Anderson, A. Ang, F. Skoulidis, J. Delord *University Hospital of Geneva, Switzerland Background & objectives: The CodeBreaK 100 trial supported approval of sotorasib, a specific, irreversible KRASG12C inhibitor, for adults with KRAS p.G12C-mutated locally advanced or meta- static non-small cell lung cancer (NSCLC) previously treated with systemic therapy. We consider acquired resistance to sotorasib. Methods: In the Phase 1/2 CodeBreaK 100 trial, patients with advanced KRAS p.G12C-mutated NSCLC received sotorasib mono- therapy 960 mg once daily. The primary endpoint was objective response rate (ORR). An exploratory endpoint examined genomic alterations, absent at baseline but present at disease progression. Plasma samples collected at baseline and progression were ana- lysed with the 23-gene Resolution Bioscience ctDx Lung™ assay. Results: The ORR in 174 sotorasib-treated patients was 41%. Median progression-free survival and median overall survival were 6.3 and 12.5 months, respectively (median 22.5-months follow-up). Of 67 patients with sequenced plasma samples, 19 (28%) exhibited at least one newly acquired genomic alteration; 7 (10%) had more than one mutation. Variants were detected across multiple genes and pathways. The receptor tyrosine kinase (RTK) genes were the most prevalent putative mechanism of resistance, with alterations apparent in 16 (24%) patients, including 6 (9%) with EGFR gene mutations. PI3K/AKT/mTOR, secondary RAS, and ERK/MAPK mutations were evident in 3 (4%), 2 (3%), and 1 (1%) patient, respectively. Six (9%) patients had undetectable tumour shedding. Conclusion: Genomic alterations observed in KRAS p.G12C- mutated NSCLC patients treated with sotorasib suggest acquired resistance can arise via a range of mechanisms; however, new RTK alterations were frequently apparent at disease progression. This highlights a potential benefit of combining sotorasib with upstream inhibitors of RTK, such as SHP2 or EGFR inhibitors. Overall, pat- terns of acquired resistance suggested by DNA analysis of plasma samples at baseline and disease progression support the develop- ment of KRASG12C inhibitor combination therapies. Funding: Amgen Inc. OFP-06-005 PD-L1 22C3 Lab Developed Test (LDT) for the Ventana’s BenchMark platform is clinically effective in NSCLC and can be used safely instead of the FDA approved DAKO platform: nation-wide experience and real-life validation (2016-2022) T. Neuman*, G. Vainer *Hadassah-Hebrew university medical centre, Jerusalem, Israel Background & objectives: PD-L1 companion diagnostic by Dako (22C3 clone), for immunotherapy patient stratification, is a com- mon requirement. Our group described a 22C3-based LDT for the Ventana platform, and showed its reliability and reproducibility (2016). However, real-time data about the reliability is lacking. Methods: Ventana’s BenchMark immunohistochemistry (IHC) platform is widely used around the world. Between July 2016 and January 2022, 1444 non-small cell lung cancer (NSCLC) patients were evaluated at the Hadassah Medical Center for PD-L1 by immunohistochemistry. All patients were evaluated by using the clone 22C3 Ventana’s BenchMark immunohistochemistry (IHC) platform as a Lab Developed Test (LDT). Results: The overall PD-L1 tumour proportion score (TPS) of ≥50%, 49-1%, and <1% of the keynote010 trial and our cohort is 28.48%, 37.89%, 33.63%, and 28.39%, 33.85%, 37.80%, respec- tively. Tumours with a PD-L1 TPS of ≥50% were not associated with patient gender, ethnicity, or biopsy type. Conclusion: Our PD-L1 22C3 Lab Develpoed Test (LDT) for the Ventana’s BenchMark platform and the Keynote 010 display simi- lar scoring distribution (strongly positive cases versus weakly or negative results) in NSCLC. Our cohort represent a nation-wide, real-time, heterogenic group, outside of clinical trial setup. This support the notion that our PD-L1 LDT is clinically effective in NSCLC and can be used safely instead of the FDA approved DAKO platform for all of the indications based on the 22C3 clone. OFP-06-006 Pulmonary asbestos fibre burden, fibre types and their effects on mortality in patients with malignant pleural mesothelioma H. Wolff*, S. Laaksonen, E. Kettunen, E. Sutinen, I. Ilonen, T. Vehmas, T. Tormakangas, J. Rasanen, M. Myllarniemi *Finnish Institute of Occupational Health, Helsinki, Finland Background & objectives: Malignant pleural mesothelioma (MPM) is associated with a dismal prognosis and is strongly related to occupational asbestos exposure. Our aim was to survey retro- spectively the asbestos fibre types and concentrations and their effect on the mortality of MPM patients. Methods: We used a national dataset of MPM patients. For this study, we included patients where an evaluation of the pulmonary asbestos fibre and type had been made using electron microscopy at the Finnish Institute of Occupational Health (FIOH). Results: A total of 590 patients were included. The median asbes- tos concentration within dry lung tissue was 3.20 million fibres/ gram (range: 0 - 1700). The most prevalent asbestos fibre types detected in lung issue were crocidolite and anthophyllite, respec- tively. In multivariable survival analyses, overall asbestos fibre concentration increased the Hazard ratio (HR) for mortality. S24