A research team at the University of Hong Kong’s LKS School of Medicine, School of Clinical Medicine (HKUMed) has developed a novel combination therapy that significantly improves treatment outcomes and survival for acute myeloid leukemia (AML) patients with FLT3 gene mutations. The study found that the combination of the FLT3 inhibitor quizartinib and the protein synthesis inhibitor omacetaxine mepesuccinate (collectively QUIZOM) can effectively suppress cancer cell proliferation, activate patients’ immune systems, and reduce the risk of recurrence while achieving an overall complete response (CRc) rate of approximately 83%.
The QUIZOM combination therapy has completed Phase 2 clinical trials, and the results have been supported through multi-omics mechanistic studies. This breakthrough represents a major advance in the treatment of high-risk blood cancers. Research results were published in an international journal nature communications.
Combination therapy increases remission rate to over 80%
Acute myeloid leukemia is a highly lethal hematological malignancy. FLT3 mutations are the most common genetic abnormality in AML, accounting for approximately 30% of cases and are associated with high recurrence rates and poor prognosis. Although current FLT3 inhibitors can temporarily improve treatment outcomes, they do not address the high risk of recurrence. Patients often require timely hematopoietic stem cell transplantation (HSCT) to prevent disease progression.
A research team led by Professor Anskar Leung Yu-hoon, Chair of the Department of Medicine, School of Clinical Medicine, University of Hong Kong, conducted a phase 2 clinical study from November 2017 to September 2020. Forty patients (aged 23 to 81 years) with FLT3 -mutant AML, all of whom were chemoresistant, were recruited and treated with QUIZOM combination therapy. The results showed a composite complete response (CRc) rate of approximately 83%, median leukemia-free survival (LFS) of 10 months, and median overall survival of 12.9 months. Thirteen of the patients underwent successful allogeneic HSCT after treatment.
QUIZOM combination therapy provides an effective and viable treatment option for patients with FLT3-mutant AML who are unsuitable for conventional chemotherapy. Improved remission rates allow patients to proceed to HSCT as consolidation therapy. With post-transplant maintenance and monitoring, the majority of patients can achieve durable remission. ”
Professor Anskar Leung Yu-hung, Head of the Department of Clinical Medicine, HKUMed
Elucidating the mechanism of overcoming drug resistance and recurrence
To better understand the therapeutic mechanism, the research team conducted multi-omics analysis and revealed the core mechanism of QUIZOM for the first time. Single-cell gene expression profiling showed that QUIZOM combination therapy interfered with cancer cells’ protein metabolism and inhibited their proliferation, while activating patients’ T-cell immune system. This study highlighted the important role of immune system activation in therapeutic efficacy and produced a dual benefit similar to that of combining chemotherapy and immunotherapy.
Additionally, the team identified a population of stem cell-like drug-resistant leukemia cells in some patients who experienced relapse. These cells acquire resistance through PLD1-mediated phospholipid metabolism, which promotes protein folding, increases survival, and ultimately leads to disease recurrence. This study confirmed that the addition of a PLD1 inhibitor can effectively suppress the regenerative function of these treatment-resistant leukemic stem cells and improve the overall therapeutic efficacy.
Obtaining patents to facilitate future clinical use
Professor Leung said: “This study demonstrates the clinical potential of QUIZOM to enable more high-risk patients to be eligible for HSCT and provides a comprehensive understanding of its mechanisms.” This provides a clear and promising therapeutic direction to overcome drug resistance in leukemia. The research team has filed a patent application for their discovery of PLD1 inhibition in leukemia, with the aim of improving treatment regimens for acute leukemia and ultimately benefiting more patients with hematological malignancies.
sauce:
University of Hong Kong
Reference magazines:
Zheng, L.-C. Others. (2026). Combination therapy of quizartinib and omacetaxine mepesuccinate in FLT3-ITD AML: a phase II study. nature communications. DOI: 10.1038/s41467-026-71186-5. https://www.nature.com/articles/s41467-026-71186-5
