81 Quick summary: A novel dual-drug combination developed by researchers in Hong Kong has achieved an impressive 83% complete remission rate in patients suffering from a highly lethal and hard to treat subtype of acute myeloid leukaemia. By disrupting cancer cell metabolism and simultaneously activating the patient’s own T cell immune system, this breakthrough medical protocol successfully bridges the gap to potentially curative stem cell transplants for high-risk individuals who are otherwise unfit for conventional chemotherapy. These clinical trial findings carry profound implications for healthcare practice and public health policy, offering a precise new therapeutic direction that directly overcomes drug resistance to enhance long-term patient survival and psychological well-being. A novel drug combination developed by researchers at the University of Hong Kong has achieved high remission rates in patients with a hard-to-treat form of acute myeloid leukaemia (AML), offering new hope for those with FLT3 gene mutations. The treatment, known as QUIZOM, pairs the FLT3 inhibitor quizartinib with the protein synthesis inhibitor omacetaxine mepesuccinate. Acute myeloid leukaemia (AML) is a highly lethal haematological malignancy. FLT3 mutations, the most common genetic abnormality in AML, account for approximately 30% of cases and are associated with a high relapse rate and poor prognosis. Although current FLT3 inhibitors can temporarily improve treatment outcomes, they do not address the high risk of relapse, and patients often require timely haematopoietic stem cell transplantation (HSCT) to prevent disease progression. Led by Anskar Leung Yu-hung, chair professor of medicine at the University of Hong Kong (HKUMed), the research team conducted a Phase 2 clinical study between November 2017 and September 2020. 40 patients aged 23–81, all with FLT3-mutated AML that was refractory to chemotherapy, were recruited and treated with the QUIZOM combination therapy. The results revealed a composite complete remission (CRc) rate of about 83%, a median leukaemia-free survival (LFS) of 10 months, and a median overall survival of 12.9 months. 13 of the patients successfully proceeded to allogeneic HSCT following treatment. Yu-hung said: “The QUIZOM combination therapy provides an effective and feasible treatment option for patients with FLT3-mutated AML who are unfit for conventional chemotherapy. By improving the remission rate, patients are better positioned to proceed to HSCT as consolidation therapy. With post-transplant maintenance and monitoring, the majority of patients can achieve sustained remission.” The findings were published in the international journal Nature Communications. To gain a deeper understanding of the therapeutic mechanisms, the research team conducted multi-omics analyses, revealing for the first time the core mechanism of QUIZOM. Single-cell gene expression profiling showed that the combination therapy disrupts protein metabolism in cancer cells, inhibiting their growth while activating the patient’s T-cell immune system. The study highlighted the essential role of immune system activation in treatment efficacy, producing a dual benefit similar to combining chemotherapy with immunotherapy. In addition, the team identified a population of stem cell-like, drug-resistant leukaemic cells in some patients who experienced relapse. These cells develop resistance via PLD1-mediated phospholipid metabolism, which facilitates protein folding and enhances their survival, ultimately leading to disease recurrence. The study confirmed that the addition of a PLD1 inhibitor can effectively suppress the regenerative function of these therapy-resistant leukaemic stem cells and improve overall treatment effectiveness. Yu-hung remarked: “This study demonstrates the clinical potential of QUIZOM, enabling more high-risk patients to become eligible for HSCT, and provides a comprehensive understanding of its mechanisms. It offers a clear and promising therapeutic direction for overcoming drug resistance in leukaemia. The research team has filed a patent application regarding the discovery of PLD1 inhibition in leukaemia, aiming to improve treatment regimens for acute leukaemia and ultimately benefiting more patients with haematological malignancies.” This breakthrough represents a significant advance in the treatment of high-risk blood cancers, particularly for patients with FLT3-ITD-mutated AML who face limited options. The combination not only targets cancer cell proliferation but also harnesses the body’s own immune response, addressing key challenges in relapse prevention. Experts note that improving bridge-to-transplant rates is critical in this patient group, where outcomes have historically been poor despite advances in targeted therapies. The trial data suggest QUIZOM could expand eligibility for potentially curative stem cell transplants. Further research is expected to build on these results, including exploration of PLD1 inhibitors to overcome resistance, as the study team continues to investigate ways to integrate this approach into broader treatment strategies for AML and related haematological malignancies. The research underscores Hong Kong’s growing role in innovative cancer therapies, with University of Hong Kong (HKUMed) contributing valuable insights into precision medicine for blood cancers. Patients and clinicians may see expanded access to such combinations as regulatory reviews and additional trials progress.