ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 disease-free survival (DFS) and overall survival (OS). Survival analyses were performed using Kaplan-Meier. Results: In this cohort of 400 patients with NSCLC, 120 were detected to harbour KRAS mutation (89% adenocarci- nomas, 10% non-specified NSCLC and 1% squamous cell car- cinoma). KRAS mutated cases encompassed 63% males and 37% females, with a median age at diagnosis of 66 years, 67% were heavy smokers (defined as greater than or equal to 30 pack-years) and 51% presented at advanced stages. KRAS- G12C was the most common KRAS mutation subtype (46%) and it was associated with a shorter median OS (p=0.006) and a tendency to associate lower DFS (p=0.14) than non-KRAS- G12C. KRAS-G12C subgroup tended to include more females, smokers and elderly patients (p=0.06-0.14) in comparison with non-KRAS-G12C. Conclusion: G12C subtype, which was the most frequent KRAS mutation in this sample, was related to aggressive behaviour and poor prognosis. No other significant differences were confirmed, except a tendency in KRAS-G12C subgroup to include more females, smokers and elderly patients in comparison with non- KRAS-G12C. Our study could enhance higher levels of accuracy estimating prognosis and response to novel targeted therapies. PS-15-023 Genomic profile of primary non-small cell lung cancer and matched mediastinal lymph nodes by next-generation sequencing: a pilot study L. Antonangelo*, C.S. Faria, R.M. Terra, E.C.T. do Nascimento, E.S. de Mello, F.R.R. Mangone, M.A. Nagai, M.E.M. Agati, V.L. Capelozzi *Universidade de São Paulo, Brazil Background & objectives: The evaluation of genomic alterations in primary resected NSCLC and matched lymph nodes can be useful in stratifying patients at risk of tumour relapse, in detecting occult metastases, and in selecting patients for adjuvant treatments. Methods: Genomic DNA (gDNA) extracted from tissue sections of six resected NSCLC (T1-2) and from samples of mediastinal lymph nodes (MLN) with negative cytology were analysed by Next Gen- eration Sequencing (NGS) with a customized SureSelect® XTHS2 kit (Agilent Tech, Santa Clara, CA, USA). Results: We observed pathogenic variants in 91.7% of the sequenced samples (six tumour and five MLN). Different genetic variants between tumour and lymph nodes were observed in five cases. Only one patient presented the same genetic alteration in both samples. Conclusion: We demonstrated different somatic pathogenic variants between the tumour tissue and the cytological negative matched lymph nodes, suggesting that these mutations were not drivers for relapse or metastases, and that different subclones carrying other mutated genes might progress to metastatic adenocarcinoma. Thus, combining molecular tests to the cytological analyses of MLN may contribute for the development of an integrative Tumour, Node, Metastasis (TNM) staging. Funding: FAPESP 2019/04416-3 PS-15-024 Concordance between FISH and NGS in detecting t(11;14) sta- tus in patients with multiple myeloma H. Avet-Loiseau, R. Thiebaut-Millot*, X. Li, J.A. Ross, C. Hader *AbbVie, France Background & objectives: The t(11;14) translocation has been identi- fied as a predictive biomarker of response to venetoclax in relapsed/ refractory multiple myeloma (MM). The objective of this study was to assess the concordance between FISH and NGS for t(11;14) detection in patients with MM. Methods: This was a retrospective, single-centre, non-inter- ventional study. Bone marrow aspirates were collected from an approved biobank with informed consent. The presence of t(11;14) was detected by FISH using the Vysis IGH/CCND1 XT DF FISH probe kit and NGS using a targeted NGS panel and NextSeq. Cohen’s Kappa was used to determine the concordance between the two diagnostic techniques. Results: A total of 130 samples were analysed for t(11;14) status; 65 at diagnosis, 60 at relapse and 5 unspecified. The samples con- sisted of 76 males and 54 females with a median age of 69 (range: 43 – 91). Both NGS and FISH detected t(11;14) in 66 samples with a concordance rate of 100% (Cohen’s Kappa=1). Concord- ance rate (100%) was consistent within the diagnostic and relapse samples. The 5 unspecified samples were t(11;14)+. There were no discordant samples. Conclusion: The results from this study demonstrate that FISH and NGS techniques have a 100% concordance rate for the detection of t(11;14) in MM patient samples. Both FISH and NGS-based testing can detect t(11;14) in patient samples allowing an individualized approach to patient care. PS-15-025 Stability of t(11;14) status by FISH between diagnosis and relapse in patients with multiple myeloma H. Avet-Loiseau, R. Thiebaut-Millot, X. Li, J.A. Ross*, C. Hader *AbbVie, USA Background & objectives: Multiple myeloma (MM) is a clonal plasma cell malignancy characterized by multistep genetic alterations and frequent relapse. We evaluated the stability of t(11;14), an early genetic event and predictive biomarker for venetoclax activity, in MM patients between diagnosis and relapse. Methods: This was a retrospective, single-centre, non-interven- tional study. Longitudinal bone marrow aspirates (BMA) from patients at different subtypes of disease (monoclonal gammopathy of undetermined significance [MGUS]; smoldering MM [SMM]); newly diagnosed MM [NDMM]; relapsed/refractory MM [RRMM]; and plasma cell leukaemia [PCL]) were collected. t(11;14) was detected using interphase FISH analysis of BMA samples enriched for plasma cells using CD138 immunomagnetic beads. Results: Among 272 patients, 118 were t(11;14)+ and 154 were t(11;14)- with a median age (years [range]) of 60 [37 – 85] and 63 [34 – 85], respectively. The median number (range) of longitudinal FISH assessments were: t(11;14)+: 2 (2 – 4); and t(11;14)-: 2 (2 – 5). All t(11;14)+ patients evaluated between diagnosis and first relapse (n = 87) remained positive with a median of 29.1 months (range, 1.9 – 149.4) between FISH assessments. All t(11;14)+ samples evaluated between diagnosis and multiple relapses (n=16) remained positive with 43.3 months (range, 11.4 – 196.9) between FISH assessments. t(11;14) was detected in MGUS/SMM patients (n=15) from diagnosis to progression (median-time: 28.7 months). Conclusion: This study is the first confirmation in a large, longitudinal cohort of patients with MM that t(11;14) is a primary genetic event that is stable across the course of disease from MGUS/SMM to MM and across lines of therapy from NDMM to RRMM. All t(11;14)+ patients remained positive from diagnosis to first and any relapse thus provid- ing confidence in this biomarker when considering t(11;14) directed treatment. No t(11;14)- patients acquired the translocation at relapse. S147