Year: 2025
Type: conference-abstract
Abstract: Introduction: Core binding factor acute myeloid leukemia (CBF-AML), defined by t(8;21)/RUNX1::RUNX1T1 or inv (16)/CBFβ::-MYH11, is categorized as favorable-risk due to its high remission rate and better relapse-free survival. We aimed to delineate the similarities and differences in treatment response and prognosis between AML patients with RUNX1::RUNX1T1 and CBFβ::MYH11 fusions. Methods: 779 de novo CBF-AML patients (511 RUNX1::RUNX1T1, 225 CBFβ::MYH11) were enrolled. Measurable residual disease (MRD) was assessed via multi-parameter flow cytometry (MFC-MRD) and quantitative polymerase chain reaction (Mol-MRD) during/after treatment. Responders are defined as achieving MRD negativity (MFC-MRD 0.01% aberrant cells and Mol-MRD > 3-log reduction) after the second consolidation cycle (C2). Otherwise, it is considered positive. Survival analyses employed Kaplan-Meier and landmark methods (3-month cutoff [corresponding to the median time of C2 completion] for immortal time bias). Treatment response comparisons used time-dependent Cox models, while relapse risks were evaluated via the Prentice, Williams and Peterson (total times) (PWP-TT) modeling. Logistics regression models were used to develop the predictive model for the responses after C2. Results: With a median follow-up of 34.6 months (range: 3.9-106.2), early mortality by C2 was lower in RUNX1::RUNX1T1 (4.7%, n=25) versus CBFβ::MYH11 (7.1%, n=18, P = 0.042) patients. The 3-year overall survival (OS) was significantly better in patients with CBFβ::MYH11 compared to RUNX1::RUNX1T1 (90.2% vs 80.6%, P = 0.011). 695 patients were evaluable for C2 assessment, with 42.5% with RUNX1::RUNX1T1(n = 206) and 33.2% with CBFβ::MYH11 fusions (n = 74) as responders. Landmark analysis showed superior 3-year OS for RUNX1::RUNX1T1responders vs. non-responders (86.3% vs. 76.5%, P = 0.008), however, responders and non-responders have comparable survival outcomes in patients with CBFβ::MYH11 (95.1% vs. 88.1%, P= 0.49). Multivariable Cox model further identified Mol-MRD positivity (HR [95%CI]: 1.96[1.08–3.54], P = 0.026) and/or MFC-MRD positivity (2.79[1.61–4.85], P<0.001) at C2 as significant risk factors for RUNX1::RUNX1T1 survival, with no associations in CBFβ::MYH11. PWP-TT model showed that non-responders at C2 were related to more relapses in the RUNX1::RUNX1T1 patients (Mol-MRD positivity: 2.126[1.181-3.828], P = 0.012; MFC-MRD positivity: 2.855[1.733-4.704], P < 0.001), but not in patients with CBFβ::MYH11 fusion. Allogeneic hematopoietic stem cell transplantation (allo-HCT) was a protective factor for long-term survival (HR [95%CI]: 0.391 [0.206-0.740], P = 0.004) with the multivariable Cox model and relapse (HR [95%CI]: 0.565 [0.386-0.828], P = 0.003) with the PWP-TT model in RUNX1::RUNX1T1 patients, but not for CBFβ::MYH11 patients. Integration of landmark analysis and time-dependent cohort allocation, we found that for RUNX1::RUNX1T1 non-responders, allo-HCT provided a superior 3-year OS compared with chemotherapy (81.9% vs. 56.4%, P < 0.001), which was different from non-responders with CBFβ::MYH11. Responders with RUNX1::RUNX1T1 or CBFβ::MYH11 had comparable outcomes when consolidated with allo-HCT or chemotherapy. Transplant in first CR provided better outcomes for RUNX1::RUNX1T1 (3-year OS: CR1-HCT 85.8% vs. non-CR1-HCT 71.4%, P < 0.001; relapses: CR1-HCT 8.3% vs. non-CR1 18.9%, P = 0.024). Consolidation therapies did not show significant impacts on long-term outcomes in CBFβ::MYH11 patients (3-year OS: Chemotherapy vs. non-CR1-HCTvs. CR1-HCT: 89.9% vs. 90.7% vs. 92,2%, P = 0.871). At last, we developed a comprehensive predictive model for C2 response incorporating clinical factors: (age < 40y [1 score], initial white blood count [<50 × 109/L: 1 score; 50-100: 2 score; > 100: 3 scores]; hemoglobin < 100 g/L [1 score]), mutational profiling (KIT D816/D822 variants [3 scores], other KIT mutations [1 score], FLT3-ITD [1 score]), as well as initial RUNX1::RUNX1T1/ABL value (<500%[4 scores], 500-1000%[3 scores], 1000-1500%[2 scores], ≥1500%[1 score]). A score ≥8 predicted non-response with 78.3% specificity and 57.4% sensitivity, effectively identifying high-riskRUNX1::RUNX1T1 AML cases needing urgent transplant evaluation. Conclusion: For CBFβ::MYH11 AML, C2 assessment offers minimal clinical significance, with allo-HCT reserved for CR2. In contrast, RUNX1::RUNX1T1 patients with post-C2 MRD positivity should receive allo-HCT at CR1.
Source: Blood
Institutions: Shanghai Jiao Tong University, Ruijin Hospital, Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, Peking University, Peking University People's Hospital, First Affiliated Hospital of Soochow University, Wuhan Union Hospital, Huazhong University of Science and Technology, First Affiliated Hospital Zhejiang University, Zhejiang University, University of Science and Technology of China
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4417021237