Abstract
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.