At the annual meeting of the American Society of Hematology (ASH), research in FLT3-ITD acute myeloid leukemia (AML) delivered important advances for clinical practice. Notably, the latest findings from the QUIWI study series further revealed that, among FLT3-ITD–negative patients, FLT3 ligand (FL) levels and microclonal status can help identify prognostic heterogeneity, offering a new paradigm for dynamic monitoring and risk-adapted intervention. On site, Oncology Frontier · Hematology Frontier invited Professor Wang Jianxiang from the Institute of Hematology, Chinese Academy of Medical Sciences, to discuss key advances, including the prognostic value of FLT3 ligand, the clinical relevance of microclonal detection, and the therapeutic potential of quizartinib, with the aim of building a comprehensive FLT3-marker–based management framework to advance AML care toward greater precision and dynamism. FLT3 Ligand Levels: A New Reference for Prognostic Assessment
Q1 Two follow-up analyses from the QUIWI trials presented at ASH, including abstract 1694, explored the prognostic significance of FLT3 ligand levels in newly diagnosed FLT3-ITD–negative AML. How do you interpret the clinical impact of soluble FLT3 ligand in this population?
Professor Wang Jianxiang: FLT3 ligand is a key regulator of hematopoiesis. Its level typically rises after chemotherapy-induced marrow injury, reflecting marrow suppression and the regenerative response of hematopoietic stem cells. Other studies have shown that leukemic cells themselves may also produce FLT3 ligand, promoting leukemic proliferation through autocrine signaling.
According to the PETHEMA group led by Solana-Altabella (ASH 2025 abstract 1694), in the QUIWI trial, FLT3-ITD–negative AML patients with plasma FLT3 ligand levels ≥1000 pg/mL on day 15 of induction achieved significantly higher CR/CRi rates and MRD-negative rates than those with levels <1000 pg/mL. Event-free survival (EFS) and duration of response (DoR) were also clearly prolonged. Pierre Peterlin and colleagues have previously suggested that high post-treatment FLT3 ligand levels may indicate effective leukemic clearance and rapid recovery of normal hematopoiesis, reflecting a favorable treatment response.
Overall, FLT3 ligand appears to be a promising biomarker for response assessment and prognostic stratification in FLT3-ITD–negative AML. High FL levels may indicate favorable prognosis, whereas low levels could suggest insufficient treatment response or residual disease.
FL-Associated Efficacy and the Added Depth from Quizartinib
Q2 High FL levels (≥1000 pg/mL) were strongly associated with higher CR rates, deeper MRD negativity, and better survival in FLT3-ITD–negative AML, while quizartinib showed a trend toward prolonging DoR in low-FL patients. How do you view these findings and their clinical significance?
Professor Wang Jianxiang:Abstract 1694 showed that FLT3-ITD–negative patients with post-induction FL ≥1000 pg/mL had a CR/CRi rate of 85.5%, compared with 64.7% in those with lower levels. Among responders, MRD negativity was also significantly higher in the high-FL group (65.8% vs. 33.3%). Median EFS and DoR were not reached in the high-FL group, whereas the low-FL group had a median EFS of about 8 months and a median DoR of approximately 14.6 months. These data reinforce the link between elevated FL levels and effective remission, likely reflecting robust marrow regeneration after leukemic clearance.
Importantly, in the QUIWI trial, quizartinib showed a trend toward extending DoR among patients with low FL levels, suggesting that quizartinib may partially overcome the poorer prognosis of this subgroup and lead to more durable responses. Given sample-size limitations, larger studies are needed to clarify the biological and prognostic implications of post-treatment FL levels.
If validated, FLT3 ligand could serve as a stratification tool: patients with high FL may have inherently better outcomes, whereas those with low FL might benefit from intensified therapy or earlier incorporation of FLT3 inhibitors. Overall, these findings highlight the potential value of FL monitoring in treatment response assessment.
Microclonal Monitoring: Early Warning for Relapse and Treatment Optimization
Q3 Evidence suggests that FLT3-ITD microclones (allelic ratio <0.05), even below conventional detection thresholds, may have clinical relevance. How do you view the biological and clinical importance of microclonal monitoring, especially in light of QUIWI subgroup analyses showing improved DoR with quizartinib in microclone-positive patients?
Professor Wang Jianxiang: Multiple studies indicate that some AML patients classified as “FLT3-ITD–negative” by standard assays may harbor very low-level FLT3-ITD subclones. In abstract 1719, these were defined as allelic ratios <0.05, and such subclones may expand at relapse and become dominant drivers. Heuser et al. (2024) reported that 10–25% of treated FLT3-ITD–negative AML patients had detectable FLT3-ITD microclones by high-depth NGS (VAF ≥0.01%), and these patients had significantly lower 2-year relapse-free survival than those without microclones.
Another PETHEMA-led QUIWI subgroup analysis (ASH 2025 abstract 1719) showed that adding quizartinib to intensive chemotherapy significantly improved outcomes in newly diagnosed FLT3-ITD–negative AML, regardless of microclone status. Notably, microclone-positive patients in the quizartinib arm had a numerically higher 4-year sustained remission rate than those receiving placebo (73.9% vs. 46.9%).
Taken together, FLT3 microclone detection has meaningful clinical implications. Incorporating microclonal assessment into baseline evaluation may help optimize individualized treatment strategies, and the use of FLT3 inhibitors such as quizartinib may improve response durability in this high-risk subgroup.
Future Directions: QuANTUM-Wild and the Evolution of FLT3-Focused AML Therapy
Q4 Based on the positive QUIWI results, the global phase III QuANTUM-Wild trial has been launched in FLT3-ITD–negative AML. As the Leading PI in China, how do you foresee future changes in FLT3-related AML treatment strategies, and where can further optimization occur?
Professor Wang Jianxiang: Following the encouraging QUIWI data, the global phase III QuANTUM-Wild trial was initiated in late 2024 to evaluate quizartinib combined with induction and consolidation chemotherapy, followed by quizartinib maintenance, in newly diagnosed FLT3-ITD–negative AML. Overall survival is the primary endpoint, and the study plans to enroll patients across approximately 260 centers worldwide, including China. As China’s Leading PI, I look forward to validating quizartinib’s clinical value and potentially expanding its indications.
If QuANTUM-Wild demonstrates clear benefit, future practice may broaden FLT3 inhibitor use beyond mutation-positive patients. Clinicians may increasingly integrate comprehensive FLT3 assessments, including FLT3 expression, ligand levels, and microclonal status. Further exploration of novel combinations—such as FLT3 inhibitors with BCL-2 inhibitors, hypomethylating agents, or immunotherapies—may deepen remissions and improve long-term survival. Optimization of consolidation and post-transplant maintenance, guided by microclonal and MRD status, may also enable more precise maintenance strategies.
In summary, as understanding of FLT3-related biomarkers advances, treatment of FLT3-ITD AML is expected to become increasingly individualized and precision-driven.
Expert Profile
Professor Wang Jianxiang Institute of Hematology, Chinese Academy of Medical Sciences
Chief Clinical Expert, Institute of Hematology, Chinese Academy of Medical Sciences Director, National Clinical Research Center for Hematologic Diseases
Professor, Chief Physician, PhD Supervisor
Tenured Professor, Peking Union Medical College National Distinguished Expert under the “Hundred-Thousand-Million Talents Program” Former Chair, 10th Committee of the Chinese Society of Hematology Vice President, Chinese Medical Doctor Association; Vice President, Hematology Branch Tianjin Distinguished Expert, Haihe Medical Scholar, First-class Tianjin Famous Doctor
With decades of experience in hematologic diseases, Professor Wang focuses on clinical and translational research in leukemia and hematologic malignancies, with extensive expertise in diagnosis and treatment.
