Xospata (gilteritinib) / Astellas - LARVOL DELTA

A NOVEL CONDITIONING REGIMEN WITH ALKYLATING AGENTS, VENETOCLAX, CYTARABINE, CLADRIBINE, AND DECITABINE (ADVANCED) FOR UPFRONT ALLOGENEIC STEM CELL TRANSPLANTATION IN ADVERSE-RISK ACUTE MYELOID LEUKEMIA PATIENTS (EHA 2025) - "Alkylating agents were administered on days -3 and -2 individually (busulfan 3.2 mg/kg (days -3 and/or -2) or thiotepa 5 mg/kg (day -3) + busulfan 3.2 mg/kg (day -2), or melphalan 100 mg/m2 (day -2) based on age, general status, and prior treatment (Figure 1)...GVHD prophylaxis consisted of cyclophosphamide 40 mg/kg (days +3 and +4), a calcineurin inhibitor (from day -1 up to day +60 - +90), and mycophenolate mofetil (from day 0 up to day +35) (Figure 1).We collected patients' and AML characteristics...The ELN 2022 adverse risk aberrations were MECOM rearrangement (1), MECOM rearrangement + TP53 mutation (1), BCR-ABL1 (1), and MDS-related mutations (6).Ponatinib and Gilteritinib were added in two cases with BCR-ABL1 and FLT3 mutations, respectively... The upfront alloSCT with ADVANCED conditioning demonstrates promissing early efficacy for newly diagnosed or R/R adverse-risk AML patients with active disease. The toxicity profile was manageable without unexpected..."

Clinical • Metastases • Acute Myelogenous Leukemia • Febrile Neutropenia • Graft versus Host Disease • Immunology • Infectious Disease • Neutropenia • Transplantation • ABL1 • BCR • FLT3 • MECOM • TP53

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

LONG-TERM FOLLOW-UP OF PREDOMINANTLY ASIAN PATIENTS WITH RELAPSED/REFRACTORY FLT3-MUTATED ACUTE MYELOID LEUKEMIA TREATED WITH GILTERITINIB VERSUS SALVAGE CHEMOTHERAPY IN THE PHASE 3 COMMODORE TRIAL (EHA 2025) - P3 | "In this phase III, open-label, multicenter study, patients with R/R FLT3mut+ AML from 48 sites in China, Malaysia, Thailand, Singapore and Russia, were randomized 1:1 to gilteritinib (120 mg/day) or SC (low-dose cytarabine; mitoxantrone, etoposide, and intermediate-dose cytarabine; or fludarabine, high-dose cytarabine, and granulocyte colony-stimulating factor). With a median follow-up of over 3 years, gilteritinib improved clinical outcomes compared with SC and was well-tolerated in a predominantly Asian population with R/R FLT3mut+ AML, consistent with the results from the primary analysis, further supporting its long-term use."

Clinical • P3 data • Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • Bone Marrow Transplantation • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • FLT3

SEQUENTIAL ALLOGENEIC STEM CELL TRANSPLANTATION FOR VENETOCLAX-EXPOSED RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA OR MYELODYSPLASTIC SYNDROME WITH INCREASED BLASTS-2 (EHA 2025) - "Three different 10-day preconditioning backbone regimens were used: ACTIVE (actinomycin D 12.5 mcg/kg (days 1-3), cytarabine 20 mg/m2 (days 1-10), venetoclax 600 mg (days 1-10), De-ACTIVE (decitabine 20 mg/m2 (days 1-10) added to ACTIVE) or De-CAVE (decitabine 20 mg/m2 (days 1-10), cytarabine 20 mg/m2 (days 1-10), venetoclax 600 mg (days 1-10)...Gilteritinib, revumenib, and BCR-ABL1 inhibitor exposure was reported in 16 % (4/25), 12 % (3/25), and 8 % (2/25), respectively...Cladribine (40 %, 10/25), gilteritinib (12 %, 3/25), trametinib (16 %, 4/25), navitoclax (28 %, 7/25), and ponatinib (8 %, 2/25) were added to the preconditioning... Upfront sequential alloSCT demonstrates high antileukemic efficacy in poor-risk, R/R AML, or MDS-IB2 patients with previous venetoclax exposure."

Acute Myelogenous Leukemia • Infectious Disease • Mucositis • Myelodysplastic Syndrome • Septic Shock • Transplantation • BCR • TP53

REAL-LIFE STUDY ON GILTERITINIB RELATED INFECTIONS (GILTERINF): AN ITALIAN SEIFEM STUDY (EHA 2025) - "Azoles (24 posaconazole, 14 isavuconazole, 1 voriconazole, 2 fluconazole) were used in 41 (36%) pts for prophylaxis/therapy of IFI and toxicities were reported mainly with 120 mg in 6 (14.6%) cases, of which one prolonged QTc and five liver/pancreatic toxicity, one of them requiring drug discontinuation. In summary, Gilteritinib therapy is not free from infectious complications, though most resolved within 30 days. IFI incidence was 13%, with 28.5% of those being breakthrough infection. The mortality rate attributable to infection was not negligible and having at least one IE/FUO emerges as a risk factor for reduced survival."

Clinical • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Nephrology • Neutropenia • Novel Coronavirus Disease • Oncology • Pneumonia • Respiratory Diseases • Septic Shock • FLT3

COVALENT FLT3 INHIBITOR BMF-500 IN RELAPSED OR REFRACTORY (R/R) ACUTE LEUKEMIA (AL): PRELIMINARY PHASE 1 DATA FROM THE COVALENT-103 STUDY (NCT05918692) (EHA 2025) - P1 | "Background: R/R FLT3m AL post-failure with gilteritinib (gilt) has a poor prognosis...Baseline features: 8 (33.3%) females, 5 (20.8%) non-whites, mean 57 yrs (23,80), median therapies 4 (1,10), HSCT 10 (41.7%), 24 (100%) with prior venetoclax (ven)...Nine (81.8%) pts showed clinical activity: decreased BM blasts (77.8%; 1 normalized blasts, 1 >50% reduction, 5 50% reduction), 4 decreased hydroxyurea use, 4 decreased transfusions... BMF-500 was well-tolerated. The majority of efficacy-evaluable pts showed reduced BM blasts, with 1 pt achieving CRi. mOS of the efficacy-evaluable FLT3m pts has not yet been reached."

P1 data • Bone Marrow Transplantation • Dermatology • Endocrine Disorders • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Hypotension • Leukemia • Neutropenia • Oncology • Pain • Pulmonary Disease • Respiratory Diseases • FLT3

RGT-61159, A POTENT AND SELECTIVE SMALL MOLECULE MYB RNA INHIBITOR, SHOWED SIGNIFICANT ANTI-TUMOR ACTIVITY AS MONOTHERAPY OR IN COMBINATION WITH STANDARDS OF CARE IN SEVERAL LEUKEMIA DISEASE MODELS HARBORING AML MOST COMMON GENETIC LESIONS (EHA 2025) - P1 | "Significant synergistic cell killing activity was observed when RGT-61159 was combined with Flt3 inhibitors (e.g. gilteritinib and midostaurin) in MOLM-13 and MV4.11 cell lines harboring Flt3 ITD mutation, and with menin inhibitors (e.g. KO-539, revemenib) in AML cell lines with NPM1 mutation or MLL-fusion. Finally, RGT-61159 in combination with a Bcl2 inhibitor (venetoclax) resulted in synergistic cell killing activity in AML cell lines carrying NPM1 mutations or AML-1-ETO fusion protein... In summary, MYB oncogene represents a therapeutic target of relevance to AML and other hematological malignancies. RGT-61159 is a potent and selective oral small molecule inhibitor of MYB RNA and protein and an attractive therapeutic avenue to treat cancers overexpressing the oncogenic MYB protein as single agent or in combination with SoC. A phase 1 study of RGT-61159 in AML / high risk MDS is planned in addition to the ongoing phase 1 study in adults with relapsed/​refractory..."

Combination therapy • IO biomarker • Monotherapy • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Targeted Protein Degradation • ABL1 • BCR • FLT3 • IDH1 • NPM1

FLAG-IDA AND VENETOCLAX IN RELAPSED / REFRACTORY ACUTE MYELOID LEUKEMIA IN AN ASIAN POPULATION (EHA 2025) - "Ten (63%) received 3+7 as first line therapy with daunorubicin 45-90mg/m2, and six (38%) received prior VEN (Figure)...One (6%) did not receive idarubicin due to reduced ejection fraction. One (6%) with NUP98/WT1 primary refractory AML relapsed with FLT3-ITD (AR 0.2) and received 14 days of gilteritinib 80mg and VEN 400mg... Our data affirms the activity of FLAG-IDA-VEN in RR AML patients. Grade ≥3 infections were frequent, but low 30-day mortality suggests that toxicity is manageable. Further work is required to establish the optimal number of cycles and doses of FLAG-IDA-VEN in populations who may have different pharmacogenomic polymorphisms to conventionally studied populations."

Clinical • Acute Kidney Injury • Acute Myelogenous Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Nephrology • Oncology • Renal Disease • Septic Shock • FLT3 • NUP98 • WT1

EFFICACY AND SAFETY OF GILTERITINIB IN R/R FLT3 ACUTE MYELOID LEUKEMIA: A REAL-WORLD STUDY (EHA 2025) - "As initial previous treatment, 77.27% had received intensive chemotherapy and 59.09% midostaurin.Median time of follow up was 9,09 months. The most frequent side effects have been fever, elevated liver enzymes and gastrointestinal symptoms.Significant haematological toxicity has been observed.Our Composite Complete Remission rates (CR + CRi) are similar to the Admiral trial. OS is slightly lower in our series but our sample has more patients with relapse than primary refractoriness, more previous exposure to FLT3 inhibitors and more intensive chemotherapy."

Clinical • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Anemia • Bone Marrow Transplantation • Musculoskeletal Pain • Neutropenia • Thrombocytopenia • FLT3

OUTCOMES OF RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA AFTER MENIN INHIBITION (EHA 2025) - "Prior to MENINi, 84% (n=43) of patients had received intensive chemotherapy (IC) and 73% (n=37) had received venetoclax (VEN)-based therapy...The most used MENINi was revumenib (n=40, 78%), followed by ziftomenib (n=9, 18%)...Of these 4 responders, 3 received AZA (azacitidine)/VEN, 1 received FLAG-IDA/VEN, and all 4 were VEN-naïve...No patients with FLT3-ITD after MENINi responded to further therapy, including 8 treated with gilteritinib (GILT), despite 4 of them being GILT-naïve... MENINi are promising in AML, but outcomes after failure are poor. Responses to post-MENINi therapy can be seen with VEN-based regimens in VEN-naïve patients. Studies focused on sequencing as well as preventing and overcoming MENINi resistance are needed."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • KMT2A • MEN1 • NPM1 • NUP98 • WT1

A META-ANALYSIS ON GILTERITINIB USING REAL-WORLD AND RANDOMIZED TRIAL DATA IN PATIENTS WITH FLT3-MUTATED REFRACTORY/RELAPSED ACUTE MYELOID LEUKEMIA. (EHA 2025) - "Our meta-analysis, which includes patients who had not been previously exposed to FLT3 inhibitors, such as those enrolled in phase 3 clinical trials, as well as patients who had received induction therapies incorporating these agents in real-world studies, suggests a general improvement in OS. The 1-year OS rate remained consistent at 36%, with no significant heterogeneity across the studies. Access to BMT enhanced by gilteritinib in about one-quarter of r/r AML patients highlighting its potential as a curative strategy whatever the care setting."

Real-world • Real-world evidence • Retrospective data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • FLT3

CONDITIONING INTENSITY, CONCURRENT NPM1 MUTATIONS, AND MEASURABLE RESIDUAL DISEASE IN PATIENTS WITH FLT3-ITD AML UNDERGOING ALLOGENEIC TRANSPLANTATION: A POST-HOC ANALYSIS FROM BMT CTN 1506 (EHA 2025) - "These data suggest that MAC may not directly eradicate FLT3-ITD MRD any more effectively than RIC, and for those patients who are FLT3-ITD MRD negative pre-HCT, there is no benefit derived from increasing conditioning intensity. For patients with NPM1 co-mutated FLT3-ITD AML, post-HCT maintenance with gilteritinib appeared to be more important than conditioning intensity for reducing relapse. Physicians managing patients with FLT3-ITD AML undergoing HCT should consider FLT3-ITD MRD and NPM1 co-mutation status when deciding on conditioning and whether or not to use post-HCT maintenance with a FLT3 inhibitor such as gilteritinib."

Clinical • Residual disease • Retrospective data • Acute Myelogenous Leukemia • Transplantation • FLT3 • NPM1

VENETOCLAX IN COMBINATION WITH CYTARABINE AND ACTINOMYCIN D (ACTIVE) FOR RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA (EHA 2025) - "Venetoclax exposure was confirmed in 13% (14/107) of cases, and 25 % (26/107) had relapsed after a previous alloSCT.Gilteritinib, trametinib, ivosidenib, ponatinib, and dasatinib were added to ACTIVE in 22 % (23/107), 4 % (4/107), 2 % (2/107), 1 % (1/107), and 1 % (1/107), respectively.The ORR was 78 % (82/105), and the CRc rate was 62 % (65/105) with 45 % (29/65) achieving MRD negativity. ACTIVE-based salvage treatment demonstrates promissing antileukemic efficacy with a high bridge-to-alloSCT rate in R/R AML."

Combination therapy • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Oncology

BIOLOGICAL ACTIVITY AND SAFETY OF GILTERITINIB IN SEQUENTIAL COMBINATION WITH CHEMOTHERAPY IN PEDIATRIC PATIENTS WITH R/R FLT3-ITD AML: INTERIM RESULTS FROM A MULTI-CENTER OPEN-LABEL PHASE 1/2 TRIAL (EHA 2025) - "Aims: This multi-center, open-label, single-arm, phase 1/2 dose escalation and expansion study examines the biological activity and safety of gilteritinib in sequential combination with fludarabine and cytarabine chemotherapy with granulocyte colony-stimulating factor (FLAG) in children, adolescents and young adults with R/R FLT3-ITD AML. Children and adolescents with R/R FLT3-ITD AML are a rare and challenging-to-treat population. Gilteritinib with FLAG chemotherapy induced remission in 5 of 9 treated patients, showing favorable biological activity and enabling transplant for 4 of these patients. This regimen was well tolerated overall with an expected safety profile consistent with delivery of myelosuppressive chemotherapy in an R/R pediatric AML population."

Clinical • P1/2 data • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Anemia • Bone Marrow Transplantation • Central Nervous System Leukemia • CNS Disorders • Febrile Neutropenia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Neutropenia • Oncology • Pediatrics • Septic Shock • Thrombocytopenia • FLT3

IDENTIFICATION OF CELLULAR MECHANISMS THAT CAN LEAD TO DRUG RESISTANCE TO FLT3 INHIBITOR GILTERITINIB IN AML (EHA 2025) - "Flt3 inhibitors currently represent important part of the AML pharmacotherapy in patients with FLT3-ITD/TKD, nevertheless, resistance to midostaurin, but also to gilteritinib (GLT) has been already reported. We have generated and characterized two gilteritinib resistant cell lines and revealed the most deregulated genes and proteins that are responsible for the transient non-FLT3 dependent resistance in HL-60 G75 and those involved in permanent resistance of FLT3 mutated MV4-11 g45 cells. Among the most deregulated processes we identified several genes that show changing expression pattern also in GLT treated AML patients and could lead to gilteritinib therapy failure in AML."

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

MULTIDRUG RESISTANCE AND METABOLIC REPROGRAMMING IN FLT3 MUTANT AML FOLLOWING PROLONGED FLT3 INHIBITOR TREATMENT (EHA 2025) - "MV4-11QR cells also showed cross-resistance to other FLT3i, including midostaurin (IC50 wt: 38.1 nM vs. QR: not reached [NR]) and gilteritinib (IC50 wt: 2.8 nM vs. QR: 65.6 nM). Given their broad resistance profile, we further investigated resistance to other AML therapies, such as venetoclax (VEN) and cytarabine (AraC)... Our findings provide evidence of cellular reprogramming following prolonged AC220 exposure. Investigating the mechanisms underlying FLT3i resistance may guide the development of combination therapies to overcome this challenge."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ACOX1 • FLT3 • PTPN1 • SOD2 • TP53

FLT3 INHIBITORS MIDOSTAURIN AND GILTERITINIB ENHANCE CYTARABINE ACCUMULATION BY AFFECTING OCTN1 AND ENT1 TRANSPORTERS IN AML CELLS (EHA 2025) - "Our findings suggest that FLT3 inhibitors significantly enhance intracellular cytarabine accumulation, most likely by affecting the intracellular trafficking of OCTN1 and ENT1 transporters in AML cells. Gaining a deeper understanding of how FLT3 inhibitors regulate these transporters could pave the way for novel therapeutic strategies, ultimately improving treatment outcomes for this AML subtype."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • SLC29A1

REM-422, A SMALL MOLECULE MYB MRNA DEGRADER, DEMONSTRATES ANTI-LEUKEMIC ACTIVITY AS A MONOTHERAPY AND IN COMBINATION WITH STANDARDS OF CARE IN PRECLINICAL MODELS OF AML (EHA 2025) - P1 | "REM-422's anti-proliferative activity was unchanged in the resistant models, which is consistent with the differentiated mechanism of action of REM-422 compared to these standards of care.The activity of REM-422 was assessed in vitro in combination with AML standards of care by co-treating leukemia cell lines with REM-422 and other agents including venetoclax, gilteritinib, revumenib, and azacitidine. These data support the therapeutic potential for REM-422 in AML patients both as monotherapy and in combination therapy."

Combination therapy • Monotherapy • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ANXA5 • CD14 • FLT3 • ITGAM • KMT2A • MYB

THE MOLECULAR BACKGROUND DETERMINES THE EXTENT BY WHICH LSD1 INHIBITORS SENSITIZE AML CELLS TO KINASE AND RAS INHIBITORS (EHA 2025) - "These cells present FLT3, NRAS and JAK2 activating mutations, respectively.Independently of FLT3 and RAS mutations, Iadademstat, sensitized 10, 8, 8 and 7 AML cell lines to gilteritinib, trametinib, pictilisib and RMC-7977, respectively...These included the phosphorylations of pNIBAN2(Ser692) and pNFIL3(Ser287)...Remarkably, gilteritinib reduced STAT5A/B phosphorylation, and iadademstat sensitised HEL cells to the JAK inhibitor ruxolitinib. In summary, the heterogeneity by which LSD1 inhibition sensitizes AML cells to FLT3, PI3K, RAS and MEK inhibitors can be rationalised by differences in how LSD1 regulates the wirings of kinase signalling networks irrespective of FLT3 and RAS mutations."

Acute Myelogenous Leukemia • FLT3 • NRAS • STAT5

HIGH-RISK CLINICAL FEATURES AND POOR OUTCOMES IN PEDIATRIC PAX5R B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA: FLT3 TARGETING AS A POTENTIAL NOVEL TREATMENT STRATEGY (EHA 2025) - "Apoptosis experiments using AnnexinV/7AAD staining, were conducted with PAX5r PDX blasts in co-colture with human bone marrow stromal cell, to test the ex vivo efficacy of gilteritinib (GILT).Overall, 58 PAX5r BCP-ALL pts were included...A tendency for slow treatment response was observed, with 20% showing poor prednisone response and 25% FCM-MRD>10% on day +15... This national retrospective study suggests that pediatric PAX5r BCP-ALL is associated with high-risk clinical features and poor outcomes. FLT3 is highly expressed in PAX5r ALL as well as in the PAX5r PDX model we generated. Ex vivo treatment with GILT showed promising single-agent efficacy and synergistic/additive effect with chemotherapy."

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • ANXA5 • FLT3 • KMT2A • PAX5 • ZNF384

TARGETING FLT3 IN B-ALL: FROM GENOMIC INSIGHTS TO THERAPEUTIC APPLICATIONS (EHA 2025) - "In vitro studies using 6 FLT3i [Gilteritinib (Gil), Midostaurin, Crenolanib, Sorafenib, Quizartibin and Ponatinib (Pon)] and Venetoclax (Ven) were conducted on pt primary cells and on 11 B-ALL wt and 4 AML cell lines (OCI-AML3 wt; MV-4-11, MOLM-13, MONO-MAC6 FLT3-mut).Data analyses highlight the heterogeneity in FLT3i sensitivity across pediatric ALL cell lines with midostaurin, Pon and quizartinib were among the top scoring drugs for most cell lines (Fig. FLT3 alterations identify a novel subgroup of TN B-ALL with therapeutic potential also in combination regimens."

Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • ABL1 • FLT3 • IKZF1 • KMT2A • NUP214 • ZNF384

Gilteritinib maintenance after allogeneic hematopoietic stem cell transplantation for relapsed/refractory acute myeloid leukemia with FLT3-internal tandem duplication mutation. (PubMed, Hematology) - "In multivariate Cox regression analysis, gilteritinib maintenance was the only factor associated with improved OS (HR = 0.395, P = 0.040) and RFS (HR = 0.447, P = 0.030). Our results indicated that gilteritinib maintenance therapy reduced the risk of relapse for FLT3-ITD mutated R/R AML. Compared with patients without maintenance therapy, gilteritinib treatment showed a similar incidence of NRM and GVHD, leading to significant survival advantages in this high-risk cohort of patients."

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

Gilteritinib inhibits PAD4 activity and neutrophil extracellular trap formation (ISTH 2025) - "On the other hand, we demonstrated that gilteritinib inhibited endogenous PAD4 activity without affecting ERK phosphorylation. Finally, no differences were observed in ROS production after activation with PMA at least during the first 30 min (slight decrease after this time) further suggesting that gilteritinib mainly inhibits NETosis through PAD4"

Antibody-mediated ratiometric delivery of FLT3 and CDK4/6 dual inhibitors for targeted treatment of acute myeloid leukemia. (PubMed, J Control Release) - "Here, we report on ratiometric codelivery of FLT3 and CDK4/6 dual inhibitors, gilteritinib and palbociclib, by daratumumab-decorated polymersomes (GIPA@DP) for high-efficacy targeted therapy of acute myeloid leukemia (AML). Selective AML-targeting in conjunction with ratiometric drug codelivery and synergistic anti-AML effects of GIPA@DP collectively led to significant survival benefits in CD38-upregulated MV-4-11 and Molm-13-Luc AML models, outperforming the nontargeted control (GIPA@P) and a mixture of two targeted single drug formulations (GI@DP + PA@DP). This targeted ratiometric delivery of dual inhibitors provides a new treatment strategy for AML and other malignancies."

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

PrE0905: Gilteritinib vs Midostaurin in FLT3 Mutated Acute Myeloid Leukemia (clinicaltrials.gov) - P2 | N=181 | Active, not recruiting | Sponsor: PrECOG, LLC. | Trial completion date: Jun 2025 ➔ Dec 2026

Trial completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • FLT3