C028 | the Evolving Picture of Clinico-genomic Features in Therapy-related Myeloid Neoplasms (t-mn) in the Last 10 Years in Italy
Year: 2025
Type: article
Abstract: t-MN include AML, MDS or MDS/MPN, developing after cytotoxic treatment for solid or lymphoid malignancies, or autoimmune diseases. Recent evidence showed that genetic features supersede previous patient history in the 2022 classifications of MN, and therapy-related is nowadays considered a “diagnostic qualifier”. Given the changes observed in cancer treatments in the last 10 years, we leveraged the Italian network to update the cartography of clinical-molecular features, treatment, and outcome of t-MNs. To-date, our study includes 488 patients diagnosed with t-MN (46% MDS and 54% AML), at 27 Italian hematological centers between 2015 and 2024. M/F ratio was 1, and median age at t-MN diagnosis 69 years (range, 20-91). The latency between cytotoxic therapy and t-MN was 60 months (IQR, 24-120). Overall, 74% of patients had received prior chemotherapy +radiotherapy (40%), including PARPinhibitors in 13% of cases. Fig.1 shows the distribution or primary cancer types. Cytogenetics was normal in 38% of cases, 4% had a “favorable-risk” t-AML (t-APL or CBF- rearranged), 13% NPM1 mut AML, 33% complex karyotypes, with chromosome 7 (6%) as the most frequent isolated alteration. TP53 was mutated in 43% of t-MN, while DNMT3A was mutated in 23%, and TET2/ASXL1 in 20% each. Overall, 34% of patients received hypomethylating agents (HMA), 21% HMA/Venetoclax, 16% CPX-351, 14% other conventional chemotherapy, and 19% were consolidated with allo-HCT. With a median follow-up of 2 years (IQR, 0.9-4.6), 44% of pts are alive. Previous disease type (hematological vs solid) influenced the genomic architecture of t-MN, with less frequent del5q (1 vs 6%, p=0.01) and NPM1 mutations (5% vs 17%, p=0.01), and increased frequency of complex karyotypes (39 vs 29%, p=0.01) and ASXL1 mutations (29 vs 14%, p=0.02). Conversely, PARPi treatment (HR=2.00, p=.02) and specific mutations (TP53, HR=3.72, p<0.01; IDH2, HR=2.19, p=0.04; JAK2, HR=2.74, p=0.03; PTPN11, HR=2.41, p=0.04) negatively influenced outcomes. Patients treated with intensive chemotherapy had better survival than those receiving HMA/Venetoclax (p=0.04). Our study provides an updated cartography of t-MN, as compared to the prior Italian Network report (PMID: 25653205). In the last 10 years, lymphoproliferative diseases are less represented among primary tumors (30% vs 38%, p=0.038), while GU tumors result overrepresented (21% vs 12%, p=0.001). Survival remains poor, despite availability of new treatments.
Authors: M.T. Voso, C. Gurnari, L. Fianchi, E. Meddi, M.S. Peris, P. Niscola, A. Spadea, M. Tomassi, A. Santoni, B. Scappini, A. Sperotto, E. Santinelli, F. Grimaldi /sup>, E. De Bellis, A. Savi, E. Crisà, E. Morsia, A. Poloni, L. Cicconi, C. Fozza, D. Nota, G. Simonetti, S. Mariani, P. Musto, A. Bruzzese, G. De Luca, P. Salutari, C. Santone, A. Curti, F. Pilo, M.P. Martelli, S. Butera, E. Diral, and A. Piciocchi
Institutions: University of Rome Tor Vergata, Agostino Gemelli University Polyclinic, Istituti di Ricovero e Cura a Carattere Scientifico, St. Eugenio Hospital, Instituto Nazionale Tumori Regina Elena, University of Siena, Azienda Ospedaliero-Universitaria Careggi, Istituto Oncologico Veneto, Università Campus Bio-Medico, Campus Bio Medico University Hospital, Federico II University Hospital, University of Naples Federico II, Azienda sanitaria universitaria Giuliano Isontina, University of Turin, Candiolo Cancer Institute, Marche Polytechnic University, University of Sassari, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Sapienza University of Rome, University of Bari Aldo Moro, Azienda Ospedaliera di Cosenza, University of Cagliari, University of Perugia, Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo, IRCCS Ospedale San Raffaele, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7093123366
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