Xospata (gilteritinib) / Astellas - LARVOL DELTA

Phase I Study of Gilteritinib for ALK-Positive Non-Small Cell Lung Cancer: Preliminary Results of Efficacy and Toxicity (IASLC-WCLC 2026) - P1 | "One patient with confirmed PR received 7 prior lines of systemic therapy and tumor was found to harbor the ALK I1171N/L1198F mutations which are predicted to convey resistance to lorlatinib and NVL-655. Early safety and efficacy data support the continued enrollment of patients onto this study. Comprehensive molecular profiling is underway to identify biomarkers that define the subgroup that would benefit from gilteritinib."

Clinical • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lung Cancer • Musculoskeletal Pain • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • AXL • CTCs • FLT3 • KIT

BMT-CTN 1506 (MORPHO): A RANDOMIZED TRIAL OF THE FLT3 INHIBITOR GILTERITINIB AS POST-TRANSPLANT MAINTENANCE FOR FLT3-ITD AML (EHA 2023) - "FLT3 inhibitors are often administered as post-HCT maintenance therapy to decrease relapse risk, but this practice is based on randomized studies of sorafenib that included patients salvaged with FLT3 inhibitors pre-transplant. Gilteritinib appears to have a clear benefit for the 50% of pts with detectable MRD pre- or post-HCT, compared to those without detectable MRD. TEAEs associated with gilteritinib were primarily myelosuppression and increased incidence of chronic GVHD. These data are among the first to support the effectiveness of MRD-based post-HCT maintenance therapy."

Clinical • Late-breaking abstract • Post-transplantation • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • Transplantation • FLT3

SOHO State of the Art Updates and Next Questions | Best of Stem Cell Transplant: Recent Advances in Allogeneic Hematopoietic Cell Transplantation. (PubMed, Clin Lymphoma Myeloma Leuk) - "The adoption of post-transplant cyclophosphamide (PTCy) as a near-universal GVHD prophylaxis backbone has diminished the long-standing primacy of human leukocyte antigen matching, enabling comparable outcomes with mismatched unrelated (MMUD) and haploidentical donors and expanding access for patients of non-European ancestry; contemporary guidelines now endorse concurrent donor searches and prioritization of younger donors...Complementary strategies, including frontline and prophylactic ruxolitinib, adoptive regulatory T-cell (Treg) therapy, and the precision-engineered Orca-T graft, are broadening the prophylaxis repertoire and beginning to separate GVHD control from the loss of immune competence and graft-versus-leukemia activity. For FLT3-ITD AML, the MORPHO trial and subsequent analyses have established measurable residual disease-directed gilteritinib maintenance, advancing a molecularly individualized approach to relapse prevention. Together, these developments..."

Journal • Review • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation • FLT3

GILTERITINIB VERSUS MIDOSTAURIN IN PATIENTS WITH NEWLY DIAGNOSED FLT3-MUTATED ACUTE MYELOID LEUKEMIA ELIGIBLE FOR INTENSIVE THERAPY: RESULTS FROM THE PHASE 3 HOVON156/AMLSG28-18/PASHA TRIAL (EHA 2026) - P3 | "Pts were randomized to induction chemo (cycle 1: standard 7+3 [cytarabine + anthracycline]; cycle 2: daunorubicin + intermediate-dose cytarabine) + either oral GILT (120 mg once daily) or MIDO (50 mg twice daily) on days 8–21. Consolidation for pts in complete remission (CR), CR with incomplete hematologic recovery (CRi) or morphologic leukemia free state (MLFS) consisted of chemo (intermediate-dose cytarabine or mitoxantrone/etoposide) + GILT or MIDO; or autologous/allogeneic hematopoietic stem cell transplantation (auto/alloHSCT) with GILT or MIDO maintenance for 1 y. Eligible pts (≥18 y) had ND FLT3 mut+ AML, ECOG PS ≤2 and were fit for intensive chemo...Summary/Conclusion Survival outcomes for GILT were not significantly different from MIDO in ND FLT3 mut+ AML, thus the primary endpoint was not met. A clinically meaningful RFS advantage with GILT vs MIDO did not translate into an OS benefit, likely due to more frequent use of GILT and alloHSCT as salvage therapy..."

Clinical • Late-breaking abstract • P3 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • FLT3 • NPM1

XY0206 targets FLT3-dependent resistance states in acute myeloid leukemia. (PubMed, J Clin Invest) - P1 | "XY0206 is a structurally optimized derivative of sunitinib, an inhibitor approved for multiple solid tumors...In primary AML blasts and xenograft models, XY0206 exhibited enhanced antileukemic activity with favorable tolerability relative to gilteritinib...Three of eight patients with prior FLT3 inhibitor-exposed R/R AML also achieved CRc. Together, these findings support further clinical evaluation of XY0206 as a FLT3-directed therapeutic in AML, particularly in disease settings with reduced sensitivity to existing FLT3 inhibitors."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • FLT3 • STAT5 • STAT5AWqe

Emergent FLT3-ITD Clone at Relapse Following Venetoclax-Based Therapy in NPM1-Mutated Acute Myeloid Leukemia (SOHO 2026) - "Objective: To describe a case of NPM1-mutated AML with acquisition of FLT3–ITD at relapse following initial MRD-negative remission with azacitidine plus venetoclax...Treatment and Outcome: When FLT3-ITD was identified during a relapse, gilteritinib and venetoclax were used as part of targeted salvage therapy... This case emphasizes the dynamic molecular evolution of NPM1-mutated AML after starting venetoclax-based therapy and highlights the importance of a thorough genomic reevaluation at recurrence. Emergent FLT3-ITD represents a clinically exploitable resistance mechanism, which directly impacts targeted therapy and transplant planning. Early detection of such clonal shifts may optimize sequencing strategies and improve outcomes in relapsed/refractory AML."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ANPEP • CD33 • FLT3 • KIT • MPO • NPM1

Phase I/II Study of Quizartinib, Venetoclax, and Decitabine Triple Combination in FLT3-ITD Mutated AML (ASH 2023) - "These patients have a median overall survival (OS) of 9.9 months when treated with the standard of care regimen (azacitidine and venetoclax). The combination of DAC + VEN + Quiz demonstrated activity in heavily pretreated and prior FLT3i-exposed (including 78% with prior gilteritinib exposure) R/R FLT3-ITDm pts, with a CRc rate of 68% and a median OS of 7.1 months. In the frontline setting, all pts achieved CRc with no early mortality, median count recovery of 40 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 • Febrile Neutropenia • Gastrointestinal Disorder • Infectious Disease • Neutropenia • Pneumonia • Respiratory Diseases • Septic Shock • FLT3

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

Azacitidine, Venetoclax, and Gilteritinib in Newly Diagnosed and Relapsed or Refractory FLT3-Mutated AML. (PubMed, J Clin Oncol) - P1/2 | "The combination of azacitidine, venetoclax, and gilteritinib resulted in high rates of CR/CRi, deep FLT3 molecular responses, and encouraging survival in newly diagnosed FLT3-mutated AML. Myelosuppression was manageable with mitigative dosing strategies."

Journal • Acute Myelogenous Leukemia • Febrile Neutropenia • Infectious Disease • Neutropenia • FLT3

Long-Term Survival Outcomes and Cytogenetic/Molecular Patterns of Relapse in Adults with FLT3-Mutated AML Receiving Frontline Triplet Therapy with a Hypomethylating Agent, Venetoclax and FLT3 Inhibitor (ASH 2024) - "The FLT3i used was gilteritinib in 61 pts (69%), quizartinib in 18 (21%), sorafenib in 7 (8%), and midostaurin in 2 (2%). A majority of relapses are driven entirely by FLT3 wild-type clones. RAS pathway mutations at diagnosis are associated with worse outcomes, and new RAS pathway mutations were observed in 20% of relapses."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BRAF • FLT3 • GATA2 • IKZF1 • KRAS • NF1 • NPM1 • NRAS • PTPN11 • RUNX1 • SF3B1 • TET2 • WT1 • ZRSR2

Actinomycin D in Combination With Low-Dose Cytarabine and Venetoclax in Relapsed or Refractory NPM1-Mutated Acute Myeloid Leukemia (SOHO 2026) - "Seventy-four percent were previously exposed to intensive chemotherapy ± midostaurin, whereas 26% were treated with HMA± venetoclax. FLT3 comutations were identified, and additional gilteritinib was used in 63% of cases... The ACTIVE regimen demonstrates promising efficacy and tolerability in R/R NPM1m AML. Further evaluation in clinical trials is warranted. CR, complete remission, CRh: complete remission with partial hematologic recovery, CRi: complete remission with incomplete hematologic recovery, CRp: complete remission with incomplete platelet counts, MLFS: morphologic leukemia-free state."

Combination therapy • Acute Myelogenous Leukemia • Colorectal Cancer • Hematological Malignancies • Leukemia • Oncology • FLT3 • NPM1

Real-World Delivery, Dose Adaptation, and Molecular Monitoring of Gilteritinib, Venetoclax, and Azacitidine in Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia. (PubMed, Clin Lymphoma Myeloma Leuk) - "GIL/VEN/AZA was feasible in selected heavily pretreated R/R FLT3-mutated AML with early marrow-guided dose adaptation. Molecular context and repeat profiling may guide subsequent therapy."

Journal • Real-world evidence • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Colorectal Cancer • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Transplantation • FLT3

Venetoclax plus intensive chemotherapy with cladribine, idarubicin, and cytarabine in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: a cohort from a single-centre, single-arm, phase 2 trial. (PubMed, Lancet Haematol) - P2 | "Venetoclax added to CLIA was safe and active in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome, producing high rates of durable MRD-negative remissions and encouraging event-free survival and overall survival."

Clinical • IO biomarker • Journal • P2 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • FLT3

Transplant Outcomes and Rates of Graft-vs-Host Disease for FLT3-ITD Acute Myeloid Leukemia by Graft Source in the Era of Posttransplant Gilteritinib Maintenance (SOHO 2026) - "Patients: Patients were included if they received reduced-intensity conditioning allo-HCT in CR from 2016 to 2024 with posttransplant cyclophosphamide. Patients with TP53 mutation and receiving post-HCT sorafenib were excluded... In FLT3-ITD AML, BM grafts were associated with less GVHD and improved GRFS vs PBSC grafts, without compromising relapse or survival. GVHD was a more frequent reason for noninitiation of gilteritinib among PBSC recipients, suggesting graft source may influence the feasibility of FLT3 inhibitor maintenance, a hypothesis warranting further evaluation. AML: acute myeloid leukemia, BM: bone marrow, CI: confidence interval, CR: complete remission, FLT3: fms related receptor tyrosine kinase 3, GVHD: graft-vs-host disease, HR: hazard ratio, ITD: internal tandem duplication, OS: overall survival, PBSC: peripheral blood stem cell, RFS: relapse-free survival, TP53: tumor protein p53."

Clinical • Post-transplantation • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • NPM1 • TP53

Survival Benefit of FLT3 Inhibitor Maintenance After Allo-HSCT in FLT3-ITD AML: A Systematic Review and Reconstructed Individual Patient Data Meta-Analysis of Randomized Controlled Trials (SOHO 2026) - " PubMed, Embase, and Scopus were systematically searched from database inception through April 2026 for randomized phase 2/3 trials evaluating FLT3 inhibitor maintenance (sorafenib, midostaurin, or gilteritinib) vs standard care alone in adults with FLT3-ITD AML in complete remission following allo-HSCT. FLT3 inhibitor maintenance after allo-HSCT was associated with significantly improved RFS and OS in adults with FLT3-ITD AML. These findings support the incorporation of posttransplant FLT3 inhibitor maintenance into treatment strategies in eligible patients. Further prospective studies are warranted to define optimal agent selection, treatment duration, and minimal residual disease-guided approaches."

Retrospective data • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Safety and Efficacy of G-CSF with Intensive Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia: A Subgroup Analysis of the Phase II Trial of Venetoclax in Combination with Cladribine, Idarubicin, and Cytarabine (ASH 2024) - P2 | "The trial allowed treating physicians to use filgrastim 300–480 µg daily for prolonged neutropenia or neutropenic fever; a trial amendment integrated pegfilgrastim at a dose of 6 mg SQ once between D5–9 of each cycle...Sixteen (18%) patients had FLT3-ITD — 8 (9%) received gilteritinib and 1 (1%) received midostaurin...FLT3-ITD AML was associated with delayed count recovery, likely due to concurrent TKI use. G-CSF use had no impact on the incidence of AML relapse."

Clinical • Combination therapy • P2 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • ASXL1 • BCOR • BCR • FLT3 • KRAS • RUNX1 • SF3B1 • SRSF2 • STAG2 • U2AF1 • ZRSR2

A Phase 1/2 Study of Gilteritinib and Momelotinib in Adults With Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia (SOHO 2026) - "Gilteritinib+momelotinib (≤600 mg daily) was safe and demonstrated encouraging preliminary activity in heavily pretreated R/R FLT3-mutated AML, including cases with prior gilteritinib and quizartinib exposure. ACVR1: activin A receptor type 1, AML: acute myeloid leukemia, CRc: composite complete remission, CRi: complete remission with incomplete hematologic recovery, FLT3: FMS-like tyrosine kinase 3, ITD: internal tandem duplication, JAK: Janus kinase, MLFS: morphologic leukemia-free state, PB: peripheral blood, R/R: relapsed/refractory, SMAD: small mothers against decapentaplegic, STAT: signal transducer and activator of transcription, TKD: tyrosine kinase domain, VAF: variant allele frequency."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Oncology • ACVR1 • FLT3 • JAK1 • JAK2 • SMAD4

Phase I/II study of decitabine/cedazuridine (ASXT727), venetoclax, and gilteritinib for patients with FLT3-mutated Acute Myeloid Leukemia or high-risk myelodysplastic syndrome (ASH 2025) - "The triplettherapy with azacitidine, venetoclax (VEN), and gilteritinib (GILT) has shown encouraging survival in FLT3-mutated AML. The combination of ASTX727, VEN and GILT is feasible but associated with myelosuppression,necessitating dose reductions."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Myelomonocytic Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Neutropenia • Pneumonia • Respiratory Diseases • Septic Shock • DNMT3A • FLT3 • KRAS • NPM1 • NRAS

PHASE 1/2 STUDY OF ORAL DECITABINE/CEDAZURIDINE WITH VENETOCLAX AND GILTERITINIB IN PATIENTS WITH NEWLY DIAGNOSED AND RELAPSED/REFRACTORY ACUTE MYELOID LEUKEMIA (EHA 2024) - P1/2 | "The combination of ASTX727 with VEN and GILT is a feasible fully oral combination for pts with FLT3mut AMLand MDS."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Respiratory Diseases • Septic Shock • DNMT3A • FLT3 • IDH2 • NPM1

Cytomolecular mechanisms of relapse after frontline FLT3 inhibitor (FLT3i)-based therapy in FLT3-mutated (mut) acute myeloid leukemia (AML). (ASCO 2025) - "Induction therapy was intensive chemotherapy (IC) in 107 pts and low intensity therapy (LIT) in 165 pts [including HMA+venetoclax(VEN)+FLT3i in 93 pts]. FLT3i's used were gilteritinib (n=105), sorafenib (n=96), quizartinib (n=54), midostaurin (n=16), and crenolanib (n=1)... Loss of FLT3 mut at relapse occurred in almost 50% of pts receiving frontline FLT3i and was more common in pts receiving IC+FLT3i or HMA+VEN+FLT3i. Common mechanisms of clonal evolution included emergent mutations in RAS pathway, WT1, and DNA methylation genes (TET2, IDH1/2). Mutational clonal evolution was less frequent in post-ASCT relapses."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • FLT3 • IDH1 • IDH2 • TET2 • WT1

10 Year Follow-up of CALGB 10603/Ratify: Midostaurin Versus Placebo Plus Intensive Chemotherapy in Newly Diagnosed FLT3 Mutant Acute Myeloid Leukemia Patients Aged 18-60 Years (ASH 2024) - "Subsequently, additional targeted drugs including gilteritinib for relapsed/refractory FLT3-mutant AML and quizartinib plus chemotherapy in untreated adults with AML with FLT3-ITD disease have gained approval...Methods : C10603 enrolled 717 pts (360 on the M and 357 on the P arm; median age 47.8 years (range 18-61), 398 women (55.5%) of whom 51.7% were randomized to M and 59.4% to P (p=0.04), and 89% white) from 2011-2015 with previously untreated AML who had either a FLT3-TKD or ITD mutation with allelic ratio of >0.05 to receive daunorubicin/cytarabine (3+7) induction (one reinduction permitted) followed by up to 4 consolidation cycles with cytarabine 3 g/m2 every 12h on days 1, 3 and 5...Conclusions : The EFS benefit of randomization to midostaurin vs placebo when added to chemotherapy was maintained over time, although the benefit for OS was diminished, likely due in part to aging. Patient and disease factors differed between early vs late relapses, which could..."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3

Venetoclax Plus Gilteritinib for FLT3-Mutated Relapsed/Refractory Acute Myeloid Leukemia. (PubMed, J Clin Oncol) - P1b | "The combination of venetoclax and gilteritinib was associated with high mCRc and FLT3 molecular response rates regardless of prior FLT3 inhibitor exposure. Dose interruptions were needed to mitigate myelosuppression."

IO biomarker • Journal • Acute Myelogenous Leukemia • Colorectal Cancer • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • FLT3

Tuspetinib Myeloid Kinase Inhibitor Safety and Efficacy As Monotherapy and Combined with Venetoclax in Phase 1/2 Trial of Patients with Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML) (ASH 2023) - "In an orthotopic mouse model of FLT3-mutant AML, tuspetinib exhibited greater antitumor activity than gilteritinib, entospletinib, venetoclax (VEN), and azacitidine (AZA) and combined favorably with VEN and AZA individually. Tuspetinib was well-tolerated and delivered single agent clinical responses across four dose levels among diverse AML genotypes; with a RP2D of 80 mg chosen for future single agent studies. Although early, the VEN/TUS combination has been well tolerated with preliminary objective responses noted."

Clinical • Monotherapy • P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • FLT3 • JAK1 • KIT • NPM1 • SYK • TP53

QUIZARTINIB WITH DECITABINE AND VENETOCLAX (TRIPLET) IS ACTIVE IN PATIENTS WITH FLT3-ITD MUTATED ACUTE MYELOID LEUKEMIA - A PHASE I/II STUDY (EHA 2022) - "Of 23 pts with R/R AML (median 3 prior Rx, 78% with ≥1 prior FLT3i including prior gilteritinib in 70%, and 39% had a prior alloSCT), 78% achieved CRc (3 CR, 15 CRi) with 6/16 and 5/18 responders achieving FLT3-PCR and multicolor flow cytometry negativity, respectively. Interestingly, RAS/MAPK mutations but not emergent TKD mutations were associated with primary and secondary resistance to the triplet. Accrual continues and updated clinical, NGS and mass cytometry (CyTOF) data will be presented."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Malignancies • Infectious Disease • Neutropenia • Respiratory Diseases • FLT3

Comparative Efficacy and Safety of FLT3 Inhibitor–Based Frontline Regimens in Newly Diagnosed FLT3-Mutated Acute Myeloid Leukemia: A Systematic Review and Network Meta-Analysis (SOHO 2026) - "Introduction: The rapid expansion of FLT3 inhibitors (FLT3i) and venetoclax (VEN)-based combinations has transformed the frontline landscape for FLT3-mutated AML...Gilteritinib-based triplets achieved the highest complete response/ complete remission with incomplete count recovery (CR/Cri) rates (OR, 3.15; 95% CI, 2.10–4.72) and measurable residual disease negativity (OR, 2.80; 95% CI, 1.65–4.75) vs midostaurin + 7+3, although OS benefit was partially offset by early mortality. For hypomethylating agent backbones, VEN + FLT3i triplets outperformed VEN + AZA (azacitidine) doublets in event-free survival (HR, 0.68; 95% CI, 0.49–0.94)... While triplet therapies offer the deepest molecular responses, quizartinib-based intensive induction currently represents the most favorable balance of survival and safety for fit patients; notably, the overall risk of bias across included studies was low. 7+3: 7 days of cytarabine and an anthracycline for the first 3 days, ASH: American..."

Retrospective data • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3