Clinical outcomes of core binding factor acute myeloid leukemia in the modern era.

Abstract

e19054 Background: Acute myeloid leukemia (AML) with alterations in core binding factor (CBF) has a favorable prognosis. The impact of complex cytogenetics or ELN 2022 adverse genetic risk markers — such as ASXL1, RUNX1, EZH2, SRSF2, (and the rest of the secondary-type mutations [STMs]) and TP53 — in CBF-AML is unclear. Additionally, treatment outcomes in CBF-AML using front-line novel approaches, such as a hypomethylating agent (HMA; decitabine or azacitidine) with venetoclax, are unknown. This study analyzed outcomes of CBF-AML with respect to higher-risk molecular and cytogenetic cohorts and treatment approaches. Methods: We identified 58 consecutive patients with CBF-AML treated at VCU Massey Cancer Center from January 1, 2013 to January 1, 2022. We used Fisher’s exact test for between-group comparisons. We analyzed survival by the Kaplan-Meier method and compared groups with the log-rank test. The date of death was used to calculate overall survival; patients were censored at the date of the last contact. Measurable residual disease (MRD) was assessed using PCR-based methods or multiparameter flow cytometry with a minimum sensitivity of 10-3. Results: We analyzed 58 patients with inv(16) or t(8;21) AML treated in the front-line setting. Seven of these patients had concomitant genetic or molecular abnormalities typically considered high risk, including complex cytogenetics or TP53mut. Forty-nine (84.5%) patients received intensive chemotherapy (IC) with FLAG, CPX-351, or conventional 7+3 with or without gemtuzumab ozogamicin; nine patients (15.5%) received lower-intensity therapies with HMAs with or without venetoclax. No differences in overall survival were seen between the patients with CBF-AML with or without complex cytogenetics or TP53mut (not reached for either cohort, median follow-up time of 6.1 y. and 5.0 y., respectively, p = 0.969). There was no difference in the rates of MRD negativity in CBF-AML with or without complex cytogenetics or TP53mut ( p = 0.544). The presence of secondary-type mutations also did not appear to significantly impact survival in CBF-AML ( p = 0.654). There was no difference in the rates of MRD negativity in CBF-AML with STMs and those without STMs ( p = 0.500). Patients that were ineligible for IC and were treated with venetoclax + HMA or HMA monotherapy had significantly reduced composite complete remission rates (CRR; CR + CRi; 25% vs 91.3%, p = 0.007) and median overall survival (3.7 m. versus not reached, p = 0.038). Conclusions: Our data confirm the superior outcomes in induction candidates of CBF-AML treated with IC. The presence of complex cytogenetics, TP53mut, or secondary-type mutations did not appear to influence the rates of MRD negativity or overall survival in CBF-AML.

Secondary-Type Mutations in Acute Myeloid Leukemia: Updates from ELN 2022

“…For example, the ELN 2022 revision classifies secondary-type mutations as adverse-risk AML but emphasizes that the risk should not be considered adverse if secondary-type signatures co-occur with favorable-risk mutations [ 2 ]. Indeed, real-world analyses from our center and others demonstrated that AML with secondary-type mutations and co-mutated NPM1 or rearrangements of the core-binding factor retain their favorable prognoses [ 7 , 8 ]. In contrast, the effects of mutational cooperation between secondary-type mutations and other mutations in the intermediate- and adverse-risk categories are less clearly defined.…”