C016 | Genomic Profiling for Clinical Decision Making in Post-polycythemia Vera and Post-essential Thrombocythemia Myelofibrosis.
Year: 2025
Type: article
Abstract: Background: Myelofibrosis (MF) encompasses primary (PMF) and secondary MF (SMF). Most PMF patients have additional non-driver myeloid neoplasms-associated cancer genes variants (CGVs), some correlated with overall survival (OS). Aims: to assess the distribution and correlations of CGVs in SMF patients of the MYSEC (MYelofibrosis SECondary) project. Methods: A myeloid-panel next generation sequencing was performed. Characteristics of study cohort and associations were described by standard statistics. Kaplan-Meier curves with log-rank tests for comparison were used for exploratory time to event analyses. A semiparametric Cox model was used for regression. Results: Out of 644 SMF cases, 429 (66.6%) reported CGVs: 234 (36.3%) one, 120 (18.6%) two, 75 (11.6%) three or more. The most prevalent CGVs were in (Figure): ASXL1 (n=191, 29.7%), TET2 (n=128, 19.9%), DNMT3A (n=43, 6.7%), EZH2 (n=33, 5.1%), SF3B1 (n=30, 4.7%), U2AF1 (n=28, 4.3%), TP53 (n=27, 4.2%), IDH1/2 (n=25, 3.9%), CBL (n=22, 3.4%), ZRSR2 (n=22, 3.4%), RUNX1 (n=21, 3.3%), NRAS (n=16, 2.5%), CSF3R (n=14, 2.2%), SRSF2 (n=14, 2.2%), and NFE2 (n=13, 2%). Phenotype-genotype correlations of CGVs will be presented. The median follow-up was 4.2 years (range, 0.6-28.1). Median OS was 9.2 years (95%CI: 8.3-11.2). Among the most prevalent CGVs, patients carrying the following ones had a significantly reduced median OS compared to those who did not: ASXL1 (7.4 vs 10.8 years, p=0.003), EZH2 (6.0 vs 9.5 years, p=0.02), U2AF1 (2.5 vs 9.7 years, p<0.001), TP53 (2.5 vs 9.2 years, p=0.002) and SRSF2 (2.0 vs 9.5 years, p<0.001). In semi-parametric Cox models including these individual CGVs and the MYSEC-Prognostic Model (MYSEC-PM), four CGVs maintained their prognostic value: ASXL1 (HR 1.53, 95%CI: 1.16-2.00; p=0.02); U2AF1 (HR 2.94, 95%CI: 1.84-4.69; p<0.0001); TP53 (HR 2.24, 95%CI: 1.31-3.81; p=0.003) and SRSF2 (HR 4.30, 95%CI: 2.32-7.94; p<0.0001). With respect to ASXL1, CGVs in U2AF1, TP53 and SRSF2 genes collectively conferred a significantly worse impact on outcome (median OS 8.2 vs 3.9 years, p<0.01), also considering the MYSEC-PM strata in a Cox model (data will be shown). Conclusion: Our study shows that genomic profiling in SMF refines current risk-stratification allowing for enhanced clinical decision making.
Authors: B. Mora, P. Guglielmelli, A. Kuykendall, M. Maffioli, F. Palandri, A. Iurlo, V. De Stefano, S. Salmoiraghi, T. Devos, F. Itri, F. Cervantes, J-J. Kiladjian, M.G. Della Porta, F. Albano, J. Gotlib, G. Benevolo, M. Caramella, M. Ruggeri, E. Rumi, D. M. Ross, C. Pessina, I. Colugnat, F. Orsini, G. Rotunno, R.S. Komrokji, D. Cattaneo, T. Barbui, D. Cilloni, L. Margotto, M. Franchi, A.M. Vannucchi, F. Passamonti
Institutions: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Florence, Moffitt Cancer Center, Aziende Socio Sanitarie Territoriale dei Sette Laghi, IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola, Agostino Gemelli University Polyclinic, Istituti di Ricovero e Cura a Carattere Scientifico, KU Leuven, Ospedale San Luigi Gonzaga, Hospital Clínic de Barcelona, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universitat de Barcelona, Hôpital Saint-Louis, IRCCS Humanitas Research Hospital, University of Bari Aldo Moro, Stanford Cancer Institute, Stanford University, Azienda Ospedaliera Citta' della Salute e della Scienza di Torino, Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda, Ospedale San Bortolo, South Australia Pathology, Royal Adelaide Hospital, Flinders Medical Centre, A. O. Ordine Mauriziano di Torino, University of Milan
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7093122873
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