Sarah Bertoli, Niklas Landberg, Emilie Bérard, Camille Gondran, Laetitia Largeaud, Véronique Mansat-De Mas, Pierre-Yves Dumas, Arnaud Pigneux, Audrey Bidet, Sylvain Garciaz, Ludovic Gabellier, Gabrielle Roth Guepin, Corentin Orvain, Pierre Peterlin, Rudy Birsen, Magda Alexis, Martin Carré, Emmanuelle Tavernier, Marion Boissard Simonet, Chantal Himberlin, Marc Maynadié, Kamel Laribi, Cécile Moluçon Chabrot, Amine Belhabri, Samy Chraibi, Quentin Cabrera, Delphine Lebon, Emmanuel Raffoux, Thomas Cluzeau, Jean-Baptiste Micol, Mathieu Leclerc, Céline Berthon, Hervé Dombret, Gunnar Juliusson, Anna Robelius, Soren Lehmann, Martin Jädersten, Lovisa Vennström, Pau Montesinos, Carmen Botella, Juan Miguel Bergua Burgues, Raimundo Garcia, Josefina Serrano, Maria Luz Amigo, Patricia García Ramirez, Claudia Lucía Sossa-Melo, Juan Manuel Alonso-Domínguez, Hartmut Döhner, Konstanze Döhner, Daniela Späth, Michael Wm Kühn, Claudia Lengerke, Hans-Jörg Tischler, Christoph Röllig, Leo Ruhnke, Christian Thiede, Andreas Burchert, Hubert Serve, Carsten Müller-Tidow, Claudia D Baldus, Jurjen Versluis, Peter Jm Valk, Daniel Tuyet Kristensen, Anne Stidsholt Roug, Jiri Mayer, Mika Kontro, Pia Ettala, Vladimir Lj Lazarevic, Christian Récher
To describe the impact of adding a tyrosine kinase inhibitor (TKI) to intensive chemotherapy (IC) on the outcome of de novo BCR::ABL1+ acute myeloid leukemia (AML), we retrospectively analyzed the data of 212 adult AML with ≥20% bone marrow blasts, BCR::ABL1+ or t(9;22)(q34.1;q11.2), no history of previous chronic myeloid leukemia and no prior exposure to BCR-ABL1 TKI. Eighty-nine patients were treated with IC alone and 123 with IC+TKI between 1999 and 2024. Complete remission (CR) or CR with incomplete hematologic recovery (CRi) was achieved in 52/77 patients (68%) with IC and 110/123 patients (89%) with IC+TKI (P<0.0001). With a median follow-up of 66.7 months, the median overall survival (OS) was 20.5 months with IC and not reached with IC+TKI. The 3-year and 5-year OS rates were 42.1% and 38.5% with IC and 70.9% and 62.9% with IC+TKI (P<0.0001) respectively. In multivariate analyses, the addition of TKI to IC was significantly and independently associated with an improved CR/CRi rate (odds ratio: 4.74 [95% confidence interval: 2.17-10.35]; P<0.001) and OS (hazard ratio: 0.40 [0.27-0.62]; P<0.001). Also, adding TKI to IC and alloHSCT in CR1 were independent prognostic factors for relapse-free survival (HR: 0.42; 95% CI: 0.23-0.75; P=0.004 and HR: 0.31; 95% CI: 0.17-0.55; P<0.0001). The outcome of de novo BCR::ABL1+ AML is strongly improved by the addition of a TKI to IC and should become the standard of care. The classification as adverse-risk should be reconsidered in the future ELN classification.