Tyrosine Kinase Inhibitors with Intensive Chemotherapy in AML with t(9;22)(q34.1;q11.2)/ BCR::ABL1 : Time to Reconsider Prognostic Risk? a Study from the Dataml Registry

Introduction De novo AML with t(9;22)(q34.1;q11.2)/ BCR::ABL1 is now a distinct entity of the ICC and WHO 2022 classifications within the group of AML with defining genetic abnormalities. This entity is distinguished from cases with history of chronic myeloid leukemia (CML) and ≥ 20% blasts, which are classified as CML in myeloid blast phase (CML-BP), although the distinction between both entities could be challenging. In the 2022 ELN classification, AML with BCR::ABL1 belong to the adverse risk group. However, this entity is very rare and generally excluded from clinical trials. Thus, there is little data on outcome especially since the era of BCR::ABL1 inhibitors (Orsmark-Pietras C et al.). In this study, we thought to describe treatments and outcome of patients (pts) with de novo AML with t(9;22)(q34.1;q11.2)/ BCR::ABL1 in comparison with CML-BP and ELN 2017 intermediate (Int) or adverse (Adv) risk AML. Methods Inclusion criteria were: pts aged ≥ 18y, included in the DATAML registry between 2000 and 2021, with either de novo BCR::ABL1 AML defined as no previous history of CML, no previous treatment with TKI and ≥ 20% blasts in bone marrow/blood or CML-BP defined as the occurrence of ≥ 20% blasts following the diagnosis of CML in chronic phase. Outcomes of pts with de novo BCR::ABL1 AML were compared with those of CML-BP pts and AML with ELN 2017 Int (n=643) or Adv (n=863) risk treated with intensive chemotherapy (IC) over the same period. A 50-gene NGS panel was retrospectively performed on available samples. Results We identified 20 pts with de novo BCR::ABL1 AML among 5819 AML (0.3%). We only studied the 18 pts who received IC. Their main characteristics were: female to male ratio (55.6%), median age (54y), extramedullary disease (47%) including splenomegaly (35%); high WBC at diagnosis; isolated t(9;22) (67%); p210 isotype (78%), mutations in ASXL1, RUNX1, NPM1, TET2, BCOR, BCORL1, DNMT3A, EZH2, IDH1, KDM6A, NF1, SMC1A, SRSF2, WT1. Comparisons with the 24 pts CML-BP who were treated with IC are shown in the Table. The main differences between both groups was a higher WBC and the presence of NPM1 mutation in de novo pts whereas ABL1 mutations were found in CML-BP only. Induction chemotherapy was mainly cytarabine and daunorubicin (45-90 mg/m²) combined with imatinib (median dose 600 mg, range 400-800). Only 2 patients did not receive imatinib because the drug was not available in 2000-2003. Those 2 pts achieved complete remission (CR) but subsequently