Vanflyta (quizartinib) / Daiichi Sankyo - LARVOL DELTA

Evaluation of the safety and efficacy of CLAG-M in combination with midostaurin or quizartinib in the treatment of AML with FLT3 mutation (HOPA 2026) - "Data collection in progress."

Clinical • Combination therapy • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • FLT3

Safety and Effectiveness of Micafungin Prophylaxis in Patients Receiving 7+3 Chemotherapy with FLT3 Inhibitor for Acute Myeloid Leukemia (HOPA 2026) - "Background/Rationale: FMS-like tyrosine kinase (FLT3) gene mutations occur in approximately 30% of patients with newly diagnosed acute myeloid leukemia (AML).1 Two FLT3 inhibitors (FLT3i), midostaurin and quizartinib, are approved for frontline treatment of FLT3-positive AML in combination with 7+3 (cytarabine plus daunorubicin/idarubicin).2 Grade 3 neutropenia is common with 7+3+FLTi therapy, necessitating invasive fungal infection (IFI) prophylaxis. These results demonstrate the safe and efficacious use of micafungin for IFI prophylaxis in patients with AML treated with 7+3+FLT3i therapy. Rates of IFIs in this cohort were similar to historical comparators utilizing mold-active azoles for antifungal prophylaxis. 5,6 Notably, most IFIs in this study were classified as possible, with rates of proven IFIs comparable to those previously reported with mold-active azoles.5,6 Additionally, rates of FLT3i dose change, induction response outcomes, and hematologic recovery were..."

Clinical • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • FLT3

Assessing Real-World Outcomes of Post-Transplant FLT3 Inhibitor Maintenance in AML (HOPA 2026) - "Objectives: The primary objective of this study is overall survival at 12 months post-transplant among patients with FLT3-mutated AML receiving sorafenib, quizartinib, gilteritinib, or midostaurin as maintenance therapy stratified by MRD and FLT-3 mutation status. Conclusions are pending."

Clinical • Post-transplantation • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Transplantation • FLT3

Actimab-A, a CD33-targeted actinium-225 radioconjugate, drives mutation-agnostic anti-leukemic activity and synergizes with standard therapies in AML through transcriptional reprogramming (AACR 2026) - "Clinical studies have shown encouraging responses when combined with CLAG-M chemotherapy in relapsed/refractory AML, including in patients with TP53 mutations or venetoclax resistance...To explore mechanisms of synergy, AML cell lines harboring common mutations (FLT3, KMT2Ar: MV-4-11, MOLM-13 cells, NPM1c: OCI-AML3, and mutant TP53: Kasumi-1, HL-60 cells) were treated for 24 hours with standard-of-care (SOC) therapies: FLT3 inhibitors (gilteritinib, quizartinib), menin inhibitors (revumenib, ziftomenib) or azacitidine alone or in combination with lintuzumab-Ac225... Lintuzumab-Ac225 shows broad mutation-independent anti-leukemic activity in AML cell lines and primary AML patient samples. When combined with standard therapies, it drives complementary transcriptional programs that enhance depth and durability of response. Together, these findings support the clinical evaluation of lintuzumab-Ac225-based combinations as a strategy to overcome resistance and enhance..."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD33 • FLT3 • KMT2A • MYC • NPM1

The FLT3 inhibitor quizartinib suppresses the WT1-driven activation of the KIT-STAT5-PIM signaling pathway and induces apoptosis in FLT3-wild type HL-60 cells (AACR 2026) - "These findings demonstrate that WT1 overexpression establishes a previously unrecognized KIT-STAT5-PIM signaling pathway that promotes AML cell survival. Importantly, this pathway creates a therapeutically exploitable vulnerability: HL-60 cells that are normally resistant to quizartinib become sensitized through WT1-induced KIT activation. Our study provides mechanistic insight into WT1-mediated leukemogenesis and suggests that KIT-targeted strategies may be effective in subsets of WT1-high, FLT3-unmutated AML."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • Wilms Tumor • AKT1 • ANXA5 • BCL2 • FLT3 • IGF2 • MYC • PIM1 • STAT5 • WT1

Daple-FLT3 gene fusion activates and localizes through a distinct mechanism from FLT3-ITD (AACR 2026) - "This leads to activation in STAT5a, AKT, and MAPK signaling, which can be modulated by the tyrosine kinase inhibitor (TKIs) sorafenib and to the most specific FLT3 inhibitor quizartinib. We further demonstrate that localization and maximal kinase activation is dependent on the Daple coiled-coil domain. These findings provide evidence that targeting Daple-FLT3 outside of its kinase domain (i.e. the coiled-coil region) may be a complementary approach with TKI therapy."

Hematological Malignancies • Leukemia • Oncology • CCDC88C • FLT3 • STAT5 • STAT5AWqe

Chromomycin A2 disrupts leukemia cell viability via integrated autophagic and apoptotic programs (AACR 2026) - "Twenty-two human blood cancer cell lines were analyzed (14 myeloid, 17 lymphoid), including resistant variants to venetoclax (n=2), quizartinib (n=1), and ATRA (n=1). These results support further preclinical development. Supported by FAPESP, CAPES, and CNPq."

Hematological Malignancies • Leukemia • Oncology • Solid Tumor • ANXA5 • SQSTM1

Quizartinib for Newly Diagnosed FLT3-ITD-Negative AML. (PubMed, J Clin Oncol) - No abstract available

Journal • Acute Myelogenous Leukemia

Reply to: Quizartinib for Newly Diagnosed FLT3-ITD-Negative AML. (PubMed, J Clin Oncol) - No abstract available

Journal • Acute Myelogenous Leukemia

Targeted Therapy in Acute Myeloid Leukemia: Current Approaches and Novel Directions. (PubMed, J Pers Med) - "Here, we detail the current targeted therapies available for AML: specifically, those targeting the BCL2 family (venetoclax), FLT3 (midostaurin, gilteritinib, quizartinib), IDH1/2 (enasidenib, ivosidenib), and MENIN (revumenib, ziftomenib). In addition, we outline potential mechanisms of resistance against these therapies, as well as efforts being taken to prevent or bypass them."

IO biomarker • Journal • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2 • FLT3 • IDH1 • IDH2

GSPT1 degrader antibody conjugate, BLB-201, for the treatment of high-risk acute myeloid leukemia (AACR 2026) - "In vivo, BLB-201 exhibited excellent synergy at low doses (0.1-0.3mg/kg) with clinical anti-AML agents (venetoclax, azacitidine and quizartinib) in systemic MV-4-11 and MOLM-13 models...We did not observe any effects of BLB-201 on normal erythroid, megakaryocytic and myeloid cell differentiation from CD34+ hematopoietic stem cells in vitro, while the CD33-targeted antibody drug conjugate, gemtuzumab ozogamacin, was highly toxic in these assays. BLB-201 DAC allows selective targeting of CD123-positive AML blasts and leukemia stem cells, minimizing direct exposure of GSPT1 degrader to healthy tissues. This unique mechanism of action may improve response rates when combined with existing targeted therapies for AML patients with high-risk or relapsed/refractory disease."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD123 • CD33 • CD34 • FLT3 • GSPT1 • IL3RA • PTPRC • TP53

Selective Mcl-1 inhibition with KS18 overcomes apoptotic resistance and enhances FLT3-targeted therapy in acute myeloid leukemia (AACR 2026) - "Here, we evaluate KS18, a highly selective small-molecule Mcl-1 inhibitor developed in our laboratory, as a single agent and in rational drug combinations in AML models (MOLM-13, MV4-11, THP-1) including a venetoclax-resistant line (MV4-11 VR)...Combination treatment with either the FLT3 inhibitor quizartinib or the multi-kinase inhibitor sitravatinib yielded strong synergistic cytotoxicity through concurrent Mcl-1 suppression and inhibition of upstream survival pathways including FLT3/STAT5, AKT, and ERK...Together, these findings identify KS18 as a promising next-generation therapeutic candidate with both single-agent efficacy and strong combination potential for overcoming drug resistance and relapse in AML. Ongoing studies are generating FLT3 inhibitor-resistant models and evaluating KS18 in vivo across diverse FLT3 mutation backgrounds to accelerate its translational development for relapsed and refractory AML."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CASP3 • FLT3 • STAT5

Low-Level Lymphoblasts in Patients with Acute Myeloid Leukemia (USCAP 2026) - "All pts received chemotherapy: 18 received HMA and venetoclax, 4 HMA alone, and 4 venetoclax alone...Targeted agents included quizartinib (n=4), gilteritinib (n=2), and gemtuzumab (n=1)... In AML patients, low-level lymphoblasts are detected rarely. When present, the lymphoblasts are predominantly of B-cell lineage, often detected at initial AML diagnosis, and are frequently associated with RUNX1 and TP53 mutations. Following AML-directed therapy, these lymphoblasts typically disappear or persist alongside AML myeloblasts without notable expansion, suggesting that the detection of lymphoblasts in the context of AML-type therapy does not require additional ALL-type therapy."

Clinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • ABL1 • ASXL1 • DNMT3A • FLT3 • IDH1 • KMT2A • MECOM • NPM1 • NRAS • NUP98 • RUNX1 • TET2 • TP53

Autophagy inhibition potentiates the antileukemic effect of FLT3 inhibitors and overcomes resistance in FLT3-ITD acute myeloid leukemia. (PubMed, Cell Death Discov) - "In FLT3-ITD AML cell lines (MOLM13 and MV4-11), treatment with first- and second-generation FLT3i (midostaurin and quizartinib, respectively) induced autophagy. The combination of quizartinib and chloroquine demonstrated a synergistic effect in MV4-11QR cells and this effect was associated with greater inhibition of the FLT3 receptor compared to the monotherapies. Therefore, combining FLT3i with autophagy inhibition enhances the FLT3i antileukemic efficacy and overcomes pharmacological resistance."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation • ATG5 • ATG7 • FLT3 • RFC4

FLT3-ITD scaffolds PKCι-STAT1 to drive noncanonical S727 phosphorylation and CD276-driven CD8+ T-cell exhaustion in AML. (PubMed, Blood) - "In patient-derived xenograft models, co-treatment with FLT3i (quizartinib) and CD276-targeting agents led to 72.9%-80.4% tumor burden reduction and enhanced CD8+ T cell function, outperforming quizartinib monotherapy. These findings define a scaffolded PKCι-pS727-STAT1 signaling axis that promotes immune evasion in FLT3-ITD AML, supporting combined FLT3 and CD276 targeting as a promising translational strategy in this aggressive leukemia subtype."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD276 • CD8 • FLT3 • IFNG • STAT1

Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trial. (PubMed, Lancet) - P3 | "The addition of quizartinib to standard chemotherapy with or without allo-HCT, followed by continuation monotherapy for up to 3 years, resulted in improved overall survival in adults aged 18-75 years with FLT3-ITD-positive newly diagnosed AML. Based on the results from the QuANTUM-First trial, quizartinib provides a new, effective, and generally well tolerated treatment option for adult patients with FLT3-ITD-positive newly diagnosed AML."

Journal • P3 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Transplantation • FLT3

FLT3-ITD measurable residual disease from the QuANTUM-First trial. (PubMed, Blood Adv) - P3 | "QuANTUM-First was a randomized trial that demonstrated that the addition of quizartinib, a potent and selective FLT3 inhibitor, to induction and consolidation chemotherapy, followed by monotherapy maintenance, improved the survival for patients with newly diagnosed FLT3-ITD (FMS-like tyrosine kinase 3‒internal tandem duplication)--mutated acute myeloid leukemia (AML)...Finally, comparison of the FLT3-ITD mutation length between the polymerase chain reaction (PCR) with capillary electrophoresis assay obtained at screening and the PCR next-generation sequencing MRD assay performed at the end of induction showed a 96.2% concordance with the exact ITD length. This trial was registered at www.ClinicalTrials.gov as NCT02668653."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • NPM1

MECHANISTIC STUDY ON NONYLPHENOL-INDUCED DEPRESSIVE-LIKE BEHAVIOR: PINK1/PARKIN-MEDIATED MITOPHAGY REGULATES SYNAPTIC REMODELING IN NEURONS (ADPD 2026) - "The cells were categorized into the following groups: (1) control (C) and low-dose NP group (LNP: 2.5µM, L), medium-dose NP group (MNP:50µM, M), and high-dose NP groups (HNP:100µM, H); (2) control (C), NP (100µM), Mdivi-1 (5µM/L), and Mdivi-1 + NP (5µM/L Mdivi-1+100µM NP) groups; (3) control (C), NP (100µM), AC220 (2nM/L), and AC220 + NP (2nM/L AC220+100µM NP) groups... Mitophagy inhibition or PKRK2 gene knockout can alleviate NP-induced downregulation of synaptic remodeling-related proteins, protect synaptic morphology and ultrastructure, and improve NP-induced depression-like behaviors."

CNS Disorders • Depression • BECN1

Polθ activity modulates sensitivity to standard therapies in DNMT3A-deficient leukemia. (PubMed, Cell Rep Med) - "Polθ inhibitors enhance the anti-leukemic effects of standard drugs such as FLT3 kinase inhibitor quizartinib, cytarabine ± doxorubicin, and etoposide in vitro and in mice with DNMT3Amut leukemia. Altogether, Polθ is an attractive target in DNMT3Amut hematological malignancies."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Targeted Protein Degradation • DNMT3A • FLT3 • MSH2 • MSH3 • PARP1 • POLQ

Differentiation Syndrome in Acute Myeloid Leukemia: Molecular Mechanisms, Clinical Spectrum, and Emerging Therapeutic Paradigms. (PubMed, Int J Mol Sci) - "While differentiation therapy revolutionized acute promyelocytic leukemia (APL) with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), its extension into non-APL AML has been limited until recent targeted agents...IDH1/2 inhibitors (ivosidenib, enasidenib, olutasidenib) yield overall response rates (ORRs) of 30-94% in AML with DS in 10-19%. Menin inhibitors (revumenib, ziftomenib, enzomenib, bleximenib) achieve ORRs of 33-88% in KMT2A-rearranged or NPM1-mutated AML, with DS in 10-25% and QT prolongation as key toxicities. FLT3 inhibitors (gilteritinib, quizartinib) improve survival in FLT3-mutated AML with DS in 1-5%...Improved recognition of DS and rational combination approaches will be essential to maximize the therapeutic benefit. Future research should address mechanisms of resistance and biomarkers to achieve cures beyond APL."

Journal • Review • Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • IDH1 • IDH2 • KMT2A • NPM1

FINAL RESULTS OF VEN A QUI TRIAL: A PHASE I-II TRIAL COMPARING VENETOCLAX WITH LOW DOSE CYTARABINE OR AZACITIDINE COMBINED WITH QUIZATINIB IN NON-FIT PATIENTS WITH ACUTE MYELOID LEUKEMIA (EHA 2025) - "Background: Quizartinib could improve complete remission (CR) and overall survival (OS) in AML patients treated with Venetoclax and LDAC or Aza combination. We established a R2PD of Quirzatinib and Venetoclax with LDAC/Aza. No differences in cCR and OS was found between LDAC and Aza. Patients with de novo AML, FLT3-ITD, NPM1 and IDH2 seems to achieve outstanding cCR and median OS."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Infectious Disease • Neutropenia • Septic Shock • Thrombocytopenia • FLT3 • IDH1 • IDH2 • NPM1 • RUNX1 • SRSF2 • TET2 • TP53

THE COMBINATION OF A FLT3-ITD, NPM1MUT AND AN EPIGENETIC REGULATORY GENE MUTATION CONFERS UNIQUE SENSITIVITY TO QUIZARTINIB: ANALYSIS FROM THE QUANTUM-FIRST TRIAL (EHA 2025) - P3 | "In pts with FLT3-ITD+ ND AML, an NPM1mut co-mutation appears to confer an additional survival benefit for those receiving Quiz. The triple-mutation of FLT3-ITD, NPM1, and an epigenetic regulatory gene, showed particular susceptibility to Quiz treatment, regardless of age, with the greatest benefit observed in pts with FLT3-ITD, NPM1mut, and DNMT3Amut. This suggests that the clinical efficacy of FLT3 inhibitors is influenced by other co-mutations, and that this triple-mutation signature represents a sub-entity of AML that is particularly sensitive to Quiz FLT3 inhibition."

Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • DNMT3A • FLT3 • IDH1 • IDH2 • NPM1 • TET2 • WT1

Azacytidine, Venetoclax Plus Minus Quizartinib for First Line Older/Unfit AML Patients (VENP-A-QUI) (clinicaltrials.gov) - P3 | N=376 | Not yet recruiting | Sponsor: PETHEMA Foundation

New P3 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

PHASE I/II STUDY OF DECITABINE, VENETOCLAX, AND QUIZARTINIB TRIPLET COMBINATION IN FLT3-ITD MUTATED AML (EHA 2025) - "Background: Patients (pts) newly diagnosed with FLT3-ITD mutated (m) acute myeloid leukemia (AML) who are ineligible for intensive induction chemotherapy (IC) experience poor outcomes with a median overall survival (OS) of 9.9 months with azacitidine+venetoclax (VEN) (Konopleva et al...With a median follow-up of 17 months, the median OS was not reached.(Figure 1).The 47 R/R AML pts were heavily pretreated (median 3 [range 1-5] prior AML therapies); 85% (40/47) had received ≥1 prior FLT3 inhibitors (FLT3i's), with 78% having prior exposure to gilteritinib and 38% having undergone prior ASCT... The combination of decitabine, venetoclax, and quizartinib demonstrated significant results in the frontline setting; 92% of pts achieved CRc with median platelet and ANC recovery of 36 and 37 days, and median OS not reached. The study continues to accrue, and updated results will be reported at the meeting."

P1/2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Infectious Disease • Neutropenia • Pneumonia • Respiratory Diseases • Septic Shock • FLT3

QUIZARTINIB AND IDARUBICIN ASSOCIATED MYOPERICARDITIS IN A PATIENT WITH AML (ACC 2026) - "For cytoreduction, idarubicin and cytarabine were initiated 7 days prior to quizartinib...Decision-Making: Quizartinib was stopped, and colchicine and guideline-directed medical therapy for heart failure were initiated... This case highlights synergistic cardiotoxicity mediated by idarubicin and quizartinib. Anthracycline-induced cardiomyocyte injury resulting in exposed cardiac antigens, followed by FLT3-mediated impaired immune tolerance, may have led to myocarditis in this patient."

Clinical • Acute Myelogenous Leukemia • Cardiovascular • CNS Disorders • Congestive Heart Failure • Depression • Heart Failure • Hypotension • FLT3