A groundbreaking therapeutic strategy has emerged from the Department of Medicine at the School of Clinical Medicine, LKS Faculty of Medicine, University of Hong Kong (HKUMed), promising to reshape the treatment landscape for acute myeloid leukemia (AML) patients harboring FLT3 gene mutations. This novel combination therapy, designated QUIZOM, pairs the potent FLT3 inhibitor Quizartinib with the protein synthesis inhibitor Omacetaxine Mepesuccinate, demonstrating remarkable efficacy in suppressing malignant cell proliferation and potentiating the patient’s immune response. The synergistic action of these agents culminates in a composite complete remission rate nearing 83%, a dramatic improvement that significantly curtails relapse rates in this high-risk patient cohort.
AML is an aggressive hematologic neoplasm marked by rapid expansion of undifferentiated myeloid blasts. FLT3 mutations, particularly internal tandem duplications (ITD), represent the most common molecular aberration found in roughly 30% of AML cases and have long been associated with poor clinical outcomes. Until now, FLT3 inhibitors have offered some therapeutic benefit, yet their impact remains transient, with high incidence of minimal residual disease and subsequent relapse. The advent of QUIZOM heralds a new era, addressing these therapeutic shortcomings by delivering enhanced remission durability and extending overall survival.
The journey toward this clinical advancement was spearheaded by Professor Anskar Leung Yu-hung, Chair Professor of Haematology at HKUMed. His team conducted an intensive Phase II clinical trial spanning nearly three years, enrolling 40 patients aged between 23 and 81 years, all identified with FLT3-mutated AML refractory to prior chemotherapy regimens. Patients received the dual-drug combination, and the trial results were striking: a CRc of approximately 83%, accompanied by a median leukemia-free survival of 10 months and an overall survival median of 12.9 months. Notably, a subset of thirteen patients proceeded to undergo allogeneic hematopoietic stem cell transplantation (HSCT), facilitated by achieving remission with QUIZOM.
This innovative regimen transcends traditional chemotherapy paradigms by integrating molecular targeting with immunomodulation. Detailed mechanistic insights were elucidated through comprehensive multi-omics approaches, including single-cell gene expression profiling, affording unprecedented resolution into the drug’s mode of action. Findings revealed that QUIZOM exerts a dual-pronged assault: it disrupts protein metabolism critical for leukemic cell viability while concomitantly invigorating T-cell mediated immune surveillance. This immune activation plays an indispensable role in achieving sustained remission, effectively mimicking the combined effects of simultaneous chemotherapy and immunotherapy.
The treatment’s efficacy, however, is met with the clinical challenge of minimal residual disease harboring therapy-resistant leukemic stem cells. The research disclosed a subpopulation of stem cell-like AML cells leveraging phospholipid metabolism mediated by phospholipase D1 (PLD1) to resist QUIZOM therapy. This metabolic adaptation facilitates protein folding and survival under therapeutic stress, fostering disease persistence and relapse. Encouragingly, preclinical data demonstrated that co-administration of a PLD1 inhibitor effectively targets these resistant clones, suggesting a promising avenue to overcome drug resistance and improve long-term outcomes.
In addressing the unmet clinical need posed by FLT3-mutated AML, QUIZOM represents not merely a therapeutic innovation but a paradigm shift. Its ability to synergistically inhibit malignant proliferation while harnessing the patient’s immune system enhances the depth and duration of remission. This alleviates the reliance on immediate HSCT, offers a safer alternative for patients unfit for intensive chemotherapy, and optimizes the pool of candidates eligible for transplantation and subsequent maintenance therapy.
Professor Leung underscored the therapeutic implications, noting that QUIZOM facilitates effective disease control enabling high-risk patients to reach HSCT consolidation—a pivotal step for durable remission. Furthermore, rigorous post-transplantation vigilance and maintenance therapies can sustain remission, exemplifying the comprehensive treatment continuum achievable with this regimen. The translational insights gleaned from molecular profiling and resistance mechanisms fortify future strategies targeting leukemic stemness and metabolic vulnerabilities.
The research team’s commitment extends beyond clinical demonstration, culminating in the submission of a patent related to the novel discovery of PLD1’s role in leukemia pathophysiology. This intellectual property paves the way for expanded therapeutic regimens integrating PLD1 inhibitors with existing AML treatments. The application of such targeted strategies embodies the forefront of precision medicine, aiming to diminish therapy resistance, hinder disease recurrence, and ultimately improve patient survival on a broader scale.
The clinical trial’s success and mechanistic revelations have garnered international recognition, culminating in the publication of these findings in the prestigious journal Nature Communications on April 6, 2026. The paper titled “Quizartinib and omacetaxine mepesuccinate combination therapy in FLT3-ITD AML: a phase II trial” documents the detailed experimental protocols, patient outcomes, and molecular analyses underscoring the therapeutic potential of QUIZOM. This contribution stands as a seminal work advancing the understanding and treatment of hematologic malignancies.
Beyond the principal investigators, including Dr. Man Cheuk-him, Dr. Zheng Lichuan, Dr. Stephen Lam Sze-yuen, and Mr. Kelvin Wong K W, the collaborative effort at HKUMed reflects interdisciplinary integration across clinical oncology, molecular biology, and pharmacology. This synergy was pivotal to deciphering complex therapeutic dynamics and resistance pathways, exemplifying the power of combining clinical trials with cutting-edge mechanistic research.
In summary, the novel QUIZOM regimen offers hope to a subset of AML patients historically burdened by dismal prognoses. Its dual mechanism targets both leukemic blasts and immune system activation while revealing metabolic vulnerabilities of resistant leukemic stem cells. This comprehensive approach marks a vital step toward overcoming relapse and transforming FLT3-mutated AML management. As further studies incorporating PLD1 inhibitors unfold, this therapeutic strategy may establish new standards of care and inspire analogous innovations across malignant hematology.
Subject of Research: Not applicable
Article Title: Quizartinib and omacetaxine mepesuccinate combination therapy in FLT3-ITD AML: a phase II trial
News Publication Date: 6-Apr-2026
Web References:
https://www.nature.com/articles/s41467-026-71186-5
http://dx.doi.org/10.1038/s41467-026-71186-5
References: Nature Communications, Volume 17, Article number: 71186 (2026)
Keywords: Acute Myeloid Leukemia, FLT3 Mutation, Quizartinib, Omacetaxine Mepesuccinate, Combination Therapy, Hematopoietic Stem Cell Transplantation, Drug Resistance, PLD1 Inhibitor, Multi-omics, Immunotherapy, Leukemic Stem Cells
