Acute Myeloid Leukemia with FLT3/ITD Mutation

Daiichi Sankyo’s Vanflyta (quizartinib) has been recommended by the National Institute for Health and Care Excellence (NICE) for certain cases of acute myeloid leukaemia (AML). The drug has been specifically recommended for routine NHS commissioning in England and Wales as an induction, consolidation and maintenance therapy for newly diagnosed FLT3-ITD-positive disease. Approximately 18,000 people are diagnosed with AML, a type of blood cancer that starts from young white blood cells in the bone marrow, every year in Europe. FLT3-ITD mutations occur in up to 30% of all AML cases and are associated with an increased risk of relapse and shorter overall survival. Vanflyta, taken orally once daily, is the first selective FLT3 inhibitor to be approved in the UK for newly diagnosed FLT3-ITD-positive AML. NICE’s decision on the drug follows an approval from the Medicines and Healthcare products Regulatory Agency in March and was supported by positive results from the late-stage QuANTUM-First trial. Results from the study showed that Vanflyta in combination with standard induction and consolidation chemotherapy, and then continued as a maintenance monotherapy, demonstrated a 22% reduction in the risk of death compared to standard chemotherapy alone. Median overall survival was 31.9 months for patients receiving Vanflyta versus 15.1 months for those in the control arm at a median follow-up of 39.2 months. Commenting on the recommendation, Haran Maheson, head of UK oncology and vice president, Daiichi Sankyo UK, said: “We are proud to have worked with NICE and NHS England to secure the first reimbursement for [Vanflyta] following health technology assessment in Europe. “UK patients with newly diagnosed FLT3-ITD positive AML can now receive a selective targeted therapy for their disease for the first time.” Sharing a similar sentiment, Colin Dyer, chief executive of UK charity Leukaemia Care, said: “We welcome the decision by NICE to approve this treatment… Patients with FLT3-ITD mutations have an increased risk of relapse with standard treatments, so another targeted treatment option for such patients is important for clinicians to tailor treatment plans to their patients effectively.”

SAN DIEGO--(BUSINESS WIRE)-- A groundbreaking research study,1 sequencing DNA samples from the Pre-MEASURE study2 strongly indicates that the detection of residual FLT3 internal tandem duplication (ITD) mutations in the blood of adult subjects with acute myeloid leukemia (AML) in first complete remission (CR) is associated with worse outcomes after post allogeneic hematopoietic cell transplant (HCT). This follow-up study performed measurable residual disease (MRD) testing on DNA of 537 subjects with FLT3-ITD AML from the Pre-MEASURE study using Invivoscribe’s RUO FLT3 ITD MRD Assay kit and bioinformatics software. Its findings underscore the likely significance of residual FLT3-ITD in first CR in predicting relapse and mortality post-transplant. A key finding from this research study was that AML subjects with residual FLT3-ITD detected prior to allogeneic HCT trended towards elevated risk of relapse and mortality post-transplant, with a dose-dependent correlation within this study population. Dr. Hourigan, Director of the Virginia Tech FBRI Cancer Research Center in Washington, DC and Principal Investigator of the study, remarked, "This research underscores the value of pre-transplant testing for residual FLT3-ITD in adults with AML. The association of MRD test results with post-transplant outcomes opens up the potential of refining treatment strategies to improve survival." Moving forward, the study calls for further research to explore alternative approaches for high-risk populations who may not benefit from current standard care protocols. Dr. Jeff Miller, CEO/CSO at Invivoscribe commented, "We are thrilled to see the remarkable association of clinical outcomes that were so clearly delineated using our research use only test and software. This research study enhances our understanding of AML monitoring and treatment." About Invivoscribe Invivoscribe is a global, vertically-integrated biotechnology company dedicated to Improving Lives with Precision Diagnostics®. For nearly thirty years, Invivoscribe has improved the quality of healthcare worldwide by providing high quality standardized research reagents, tests, and bioinformatics tools to advance the field of precision medicine. Invivoscribe has a successful track record of partnerships with global pharmaceutical companies interested in developing and commercializing companion diagnostics, and provides expertise in both regulatory and laboratory services. Providing distributable kits, as well as clinical trial services through its globally located clinical lab subsidiaries (LabPMM), Invivoscribe is an ideal partner from diagnostic development, through clinical trials, regulatory submissions, and commercialization. For additional information, please visit or contact us at inquiry@invivoscribe.com and follow us on Linked In. 1. Measurable Residual FLT3 Internal Tandem Duplication Before Allogeneic Transplant for Acute Myeloid Leukemia, Dillon et al, JAMA Oncology, Published online May 2, 2024. 2. DNA Sequencing to Detect Residual Disease in Adults with Acute Myeloid Leukemia Prior to Hematopoietic Cell Transplant, Dillon et al, JAMA 2023; 329 (9): 745-755

Daiichi Sankyo’s quizartinib is indicated for use as a first-line treatment in adults with acute myeloid leukaemia. Credit: Nemes Laszlo / Shutterstock.com. The UK Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing authorisation to Daiichi Sankyo for quizartinib (Vanflyta) for use as a first-line treatment in adults with acute myeloid leukaemia (AML) with a FLT3-ITD mutation. The decision allows for the oral administration of quizartinib in combination with chemotherapy – a significant development in the treatment of AML. Taken once daily, quizartinib targets tyrosine kinases to hinder the growth of abnormal bone marrow cells. The treatment duration and dosage are determined by the prescribing physician and may continue post-chemotherapy. The approval is backed by a double-blind, randomised, placebo-controlled Phase III clinical trial in 539 adult subjects aged between 18 and 75 years with newly diagnosed FLT3-ITD positive AML. See Also: MHRA approves Marinus’ ganaxolone for CDKL5 deficiency disorder Innovent’s ROS1 TKI is one step closer to winning the Chinese NSCLC market The study demonstrated a statistically significant improvement in overall survival (time from randomisation to death from any cause) for patients who received quizartinib. Patients receiving quizartinib had a median overall survival of 31.9 months compared to 15.1 months for those receiving a placebo. Abnormal liver enzymes, low blood platelet and white blood cell levels, anaemia, diarrhoea, nausea, stomach pain and headache were the most common side effects linked to the trial. MHRA Healthcare Quality and Access interim executive director Julian Beach stated: “ Our key priorities are keeping patients safe and enabling their access to high quality, safe and effective medical products. “We’re assured that the appropriate regulatory standards for the approval of this medicine have been met. As with all medicines, we will keep its safety under close review.” In another development, the MHRA also gave marketing authorisation to Pfizer for etrasimod (Velsipity) for the treatment of moderately to severely active ulcerative colitis. Etrasimod is prescribed as a long-term treatment and should be initiated only under a doctor’s supervision. The approval is supported by two clinical studies, ELEVATE UC 52 and ELEVATE UC 12, indicating its efficacy for patients where standard treatments were inadequate. The UK National Institute for Health and Care Excellence (NICE) has also published a final guidance recommending etrasimod for ulcerative colitis. With the NICE recommendation, more than 25,000 people in England will be eligible to receive the treatment. The latest development comes after the MHRA approved Marinus Pharmaceuticals ’ ganaxolone, marketed as Ztalmy, an anti-seizure medication for cyclin-dependent kinase-like 5 (CDLK5) deficiency disorder .