Rojek, Alexandra E

We investigated the prognostic impact of blast counts, TP53 allelic state determinants (number of hits, del(17p), variant allele frequency, complex karyotype),and a novel karyotypic clonal cell fraction (≤50% clonal cells vs >50% clonal cells (termed ‘CK50’)) in 495 individuals with TP53- mutated ( TP53 MUT ) myeloid neoplasms. Outcome examined was 24-month survival (OS24). The cohort (median age 71) included 29% (144/495) myelodysplastic syndromes (MDS)/MDS-acute myeloid leukaemia (AML) (1%–19% blasts) and 71% (351/495) AML (≥20% blasts), with 18% (81/460) having low CK50. Overall, 83% received front-line hypomethylating agents. Higher blast counts (<20% vs ≥20%) were marginally associated with CK50 (p=0.08). In the OS24 analysis, blast count showed a marginal association with OS24 (HR 1.3 (95% CI 1.0 to 1.6); p=0.07), while CK50 predicted significantly inferior outcomes (HR=1.7 (95% CI 1.2 to 2.3); p=0.002). In a multivariable model including all TP53 allelic state determinants, only CK50 and complex karyotype remained relevant for predicting adverse outcomes.

AbstractCore‐binding factor acute myeloid leukemia (CBF‐AML) is characterized by the presence of inv(16)/t(16;16) or t(8;21) and is classified as a favorable risk by the 2022 European LeukemiaNet (ELN) guidelines. The CD33‐targeting antibody‐drug conjugate, gemtuzumab ozogamicin (GO), is commonly added to intensive chemotherapy (IC) in CBF‐AML. We sought to compare outcomes in patients treated with IC with or without GO in CBF‐AML. We included 200 patients with CBF‐AML treated with IC across seven academic centers. Induction treatment regimens were categorized as IC alone, IC with GO, or IC with KIT inhibitor (dasatinib or midostaurin). Median follow‐up for the whole cohort was 2.5 years. Three‐year overall survival (OS) was 70% and 3‐year event‐free survival (EFS) was 51%. Patients treated with IC with GO experienced a 3‐year EFS of 50% compared to those treated with IC alone who experienced a 3‐year EFS of 47%, with no statistically significant difference (p = 0.62). Similarly, those treated with IC with GO did not experience an improved OS compared to those treated with IC alone (p = 0.67). Patients treated with IC with KIT inhibitor experienced a significantly improved 3‐year EFS of 85% compared to those with IC with or without GO (p = 0.04). We find in our study that there is no survival benefit in patients treated with IC with the addition of GO; improved EFS was seen in patients with CBF‐AML treated with IC plus KIT inhibitors, consistent with outcomes noted in prospective studies utilizing this approach.