The Differential Impact of Secondary-Type Mutations in a Multinational Cohort of 5311 Intensively Treated Acute Myeloid Leukemia Patients

• Published in: Blood 2024-11, Vol.144, p.2934-2934
• Main Authors: Eckardt, Jan-Niklas, Bill, Marius, Döhner, Konstanze, Rausch, Christian, Metzeler, Klaus H, Spiekermann, Karsten, Stasik, Sebastian, Sauer, Tim, Scholl, Sebastian, Hochhaus, Andreas, Crysandt, Martina, Brummendorf, Tim H. H., Krug, Utz, Wörmann, Bernhard, Einsele, Hermann, Hiddemann, Wolfgang, Görlich, Dennis, Sauerland, Maria Cristina, Steffen, Björn, Neubauer, Andreas, Burchert, Andreas, Schaefer-Eckart, Kerstin, Berdel, Wolfgang E., Schliemann, Christoph, Krause, Stefan W., Hänel, Mathias, Hanoun, Maher, Kaufmann, Martin, Fransecky, Lars, Braess, Jan, Schetelig, Johannes, Middeke, Jan Moritz, Bullinger, Lars, Heuser, Michael, Thol, Felicitas R, Serve, Hubert, Baldus, Claudia D, Platzbecker, Uwe, Mueller-Tidow, Carsten, Weinbergerova, Barbora, Mayer, Jiri, Dumas, Pierre-Yves, Bertoli, Sarah, Delabesse, Eric, Récher, Christian, Pigneux, Arnaud, Herold, Tobias, Ganser, Arnold, Döhner, Hartmut, Bornhäuser, Martin, Thiede, Christian, Röllig, Christoph
• Format: Article
• Language: English
• ISSN: 0006-4971
• DOI: 10.1182/blood-2024-201945

Secondary-type mutations (STM) are defined as alterations in ASXL1, BCOR, EZH2, SF3B1, SRSF2, STAG2, U2AF1, and ZRSR2 in the recent update of the WHO classification on myeloid neoplasms. The International Consensus Classification (ICC) extends its definition to also include alterations of RUNX1. Patients bearing STMs are considered adverse risk in the absence of other class-defining markers according to the recent update of the European LeukemiaNet (ELN) 2022 recommendations. However, it is unclear if all STMs convey an equally adverse prognostic effect or if individual STMs have a differential prognostic impact. We pooled data on molecular genetics, cytogenetics, and outcomes of 5311 newly diagnosed and intensively treated AML patients from previous randomized multicenter trials of the German SAL (n=1606), the German-Austrian AMLSG (n=1354, dataset from Gerstung et al., Nature Genetics 2017), the German AMLCG (n=1138), the French DATAML (n=1040), and the Czech CELL (n=173). Patients were retrospectively categorized into ELN2022. All analyses were carried out for WHO 2022 definitions (STMWHO) and ICC 2022 definitions (STMICC). We found 1485 (28%) of patients to harbor STMWHO and 1698 patients (32.0%) with STMICC. Patients with STMWHO and STMICC were significantly older than non-STM patients (median 60 vs 53 and 59 vs 52 years, p