midostaurin / Generic mfg. - LARVOL DELTA

FLT3 testing and guideline concordance in Acute Myeloid Leukemia across an Indiana health system (ASH 2025) - "Current guidelines recommend FLT3 mutation testing at diagnosis to inform risk stratification and guide the use of FLT3 inhibitors such as midostaurin, quizartinib, and gilteritinib...The most frequently used induction therapies included venetoclax in combination with a hypomethylating agent (30%), 7+3 (15.7%), and a combination regimen consisting of fludarabine, cytarabine, idarubicin, and granulocyte colony-stimulating factor (FLAG IDA; 13.8%)... FLT3 testing was commonly performed in this cohort, yet notable variability in guideline adherence was observed. Guideline-concordant induction regimen selection was marginally higher for patients with FLT3 mutations. These findings underscore the need for institutional quality improvement initiatives aimed at enhancing the documentation of FLT3 status and optimizing the integration of guideline-directed therapies in AML management."

Discordant • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • FLT3

Prognostic relevance of multiparameter flow cytometry-based MRD assessment in patients with FLT3-ITD mutated AML considering concomitant mutations including DNMT3A/NPM1/WT1 mutation (ASH 2025) - "Seventy-two patients (80%) received intensive chemotherapy with midostaurin used in combination for 60 patients (83.3%)...MFC-MRD negativity showed better RFS compared to MFC-MRD positivity. However, larger studies are needed to clarify the prognostic impact of MFC-MRD within specific co-mutational subgroups."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • DNMT3A • FLT3 • NPM1 • WT1

Enhanced risk stratification in AML through integrated mutation and CNV profiling: Insights from Uruguay (ASH 2025) - "All received 7+3 chemotherapy; 21% also received midostaurin...Treatments included azacitidine alone (43.5%) or with venetoclax (47.8%), achieving CR/CRi in 56.1%... This is the first comprehensive study to evaluate both somatic mutations and CNVs through targeted NGS in Uruguayan AML patients, and one of the few such efforts in Latin America, where available data are limited to small series from Brazil and Mexico. Conducted nationwide in a country with ~100 new AML cases per year, this cohort is representative and contributes valuable regional insight. Incorporating CNV analysis via NGS significantly improved the detection of clinically relevant genetic abnormalities."

Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • CEBPA • DNMT3A • FLT3 • IDH1 • IDH2 • NPM1 • NRAS • RUNX1 • SRSF2 • STAG2 • TP53

High-intensity purine analogue-based therapy for refractory/relapsed Acute Myeloid Leukemia (RR-AML): A single-institution experience (ASH 2025) - "For medically fit patients, high-intensity salvage regimens such as CLAG or FLAG-IDA incorporate purine analogues (cladribine or fludarabine) with high-dose cytarabine and granulocyte colony-stimulating factor (G-CSF), achieving complete remission (CR) rates between 30% and 60% in the relapsed setting...Five patients (29%) received FLAG-IDA (2 of them received a concomitant FLT3 inhibitor: midostaurin and quizartinib), 7 patients (41%) received FLAG-IDA + venetoclax, 4 (24%) received CLAG-IDA + Venetoclax, and 1 patient (6%) received CLAG + VEN... Our single-institution experience demonstrates that high-intensity purine analogue-based therapy is safe and active in patients with RR-AML and can achieve meaningful remission rates in a heavily pretreated, predominantly adverse risk population. These outcomes compare favorably to historic expectations and support the use of purine analogue regimens as an effective salvage strategy. Prospective studies and continued real-world..."

Clinical • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • FLT3 • IDH1 • TP53

Comparative safety and efficacy of first- and second-generation FLT3 inhibitors in newly diagnosed and relapsed AML: A meta-analysis stratified by molecular biomarkers (ASH 2025) - "First-generation (sorafenib and midostaurin) and second-generation (gilteritinib, quizartinib, and crenolanib) FLT inhibitors demonstrated efficacy and safety across disease stages and are now used as a standard of treatment for FLT3-mutated AML. Conclusions Second-generation FLT inhibitors exhibit enhanced efficacy in relapsed-refractory AML scenarios and comparable outcomes to first-generation inhibitors in newly diagnosed AML.Stratification using ITD allelic ratio and NPM1 co-mutation is emerging as a critical factor. In light of these findings, it's imperative to integrate second-generation inhibitors in salvage settings and Biomarker-guided treatment decisions in front-line FLT3 mutant-AML"

Biomarker • Retrospective data • Acute Myelogenous Leukemia • Cardiovascular • Hematological Disorders • Hypertension • Neutropenia • FLT3 • NPM1

High vs. low intensity chemotherapy in AML: Survival and transplant outcomes in a brazilian experience (ASH 2025) - "Although the treatment landscape for acute myeloid leukemia (AML) has evolved with the incorporation of targeted therapies—such as midostaurin for FLT3-mutated disease—patients are still stratified based on eligibility for intensive chemotherapy. High-intensity treatment typically involves an anthracycline plus cytarabine backbone, followed by allogeneic bone marrow transplantation (alloBMT) in first remission for those with high-risk disease, as defined by the European LeukemiaNet (ELN) classification... As expected, patients eligible for high-intensity chemotherapy were generally younger and had fewer comorbidities, achieving better outcomes. Nonetheless, this single-center Brazilian study reinforces the favorable impact of alloBMT on AML outcomes, regardless of induction intensity. These findings are particularly relevant in settings with limited access to clinical trials, highlighting the importance of transplant strategies in real-world practice."

IO biomarker • Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Transplantation • FLT3

Multi-omics analysis identifies neutrophil degranulation as a PSMD3-regulated pathway in FLT3-mutated AML (ASH 2025) - "Despite the revolutionary development of FLT3-targeted tyrosine kinase inhibitors (TKIs) such as Midostaurin, drug resistance continues to pose a clinical obstacle... Neutrophil degranulation emerged as the consistently dysregulated pathway across our proteomics, RNA sequencing, and scRNAseq data, suggesting a potential mechanism for PSMD3 in AML. The reduction of PSMD3 not only disrupted immune-related pathways but also reprogrammed key metabolites. Altogether, these data indicate that PSMD3 regulates neutrophil degranulation, immune-related pathways, and metabolic reprogramming, and may be a novel therapeutic target in FLT3+ AML and possibly other cancers."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Targeted Protein Degradation • ANXA5 • FLT3 • PSMD3

Unveiling FLT3 in B-ALL: Molecular drivers and targeted treatment opportunities (ASH 2025) - "In vitro assays withincreasing concentrations of 6 FLT3i for 24, 48, 72h [Gilteritinib (Gil), Midostaurin, Crenolanib, Sorafenib,Quizartinib, Ponatinib (Pon)] and Venetoclax (Ven) were performed on primary patient samples (n=29; FLT3-mut n=5/29), 11 B-ALL wt cell lines, 2 B-ALL mut (NALM6-mut, KASUMI-10), and 4 AML cell lines (OCI-AML3 wt; MV-4-11, MOLM-13, MONO-MAC6 FLT3-mut). FLT3 alterations define a novel Ph-negative B-ALL subgroup withtherapeutic relevance. Given the responses in FLT3-wt in addition to the mutated models, FLT3i may alsobenefit patients without FLT3 muts. Thanks to: Ricerca Corrente by the Italian MoH L3P1946 andAILTreviso."

Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • T Acute Lymphoblastic Leukemia • FLT3 • IKZF1 • KMT2A • PBX1 • TCF3 • TP53 • ZNF384

Prognostic implications of commutational patterns in NPM1-mutated AML receiving intensive treatment. cetlam group study (ASH 2025) - "Furthermore, prognosis may have been improved by the addition of midostaurin (MIDO) totreatment in FLT3mut patients and gentuzumab ozogamizine (GO) in FLT3wt patients... In this study, in patientswith NPM1mut AML treated with IC +/- MIDO or GO, the comutations analyzed were not associated withOS or DFS. However, mutations in DNMT3A and TET2 showed a tendency to be associated with a lowerlikelihood of CR. Age and functional status at diagnosis were confirmed as."

Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Infectious Disease • Leukemia • DNMT3A • FLT3 • IDH1 • IDH2 • NPM1 • PTPN11 • RAD21 • TET2 • TP53

Anti-leukemic efficacy of a novel inhibitor for KMT2A-r/FLT3-driven AML via multi-kinase targeting and synergy with menin inhibition (ASH 2025) - "Synergistic activity with the FDA-approved menin-irevumenib was examined using proliferation assays, immunoblotting, flow cytometry, and qRT-PCRanalyses. LGR3922 demonstrated potent inhibition of oncogenic FLT3 and additional target kinases,resulting in suppressed proliferation and enhanced apoptosis in vitro...In an Mll-ENL knock-in-based NOD.SCID mouse model, LGR3922significantly decreased the Mll-ENL leukemic allelic burden compared to midostaurin... LGR3922 represents a promising candidate for targeted therapy in KMT2A-r/FLT3mut AML,offering a unique multi-kinase mechanism that disrupts key signaling pathways not targeted by currenttherapies. Demonstrated in vivo efficacy, favorable toxicity profile, and synergistic activity with menin-isupport its further development and testing. Since one of the common side effects of menin-i therapy isanemia, the observed erythropoiesis-stimulating effect of LGR3922 as an unexpected side effect could beadvantageous for therapeutic..."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • CDK1 • EIF4E • FLT3 • HDAC4 • HOXA9 • KMT2A • MEF2C • MEIS1 • STAT5

Improved overall survival in patients with advanced systemic mastocytosis treated with avapritinib versus real-world therapy based on mutation-adjusted risk score (MARS) stratification (ASH 2025) - P=N/A, P1, P2 | "This analysis builds on the earlier work, comparing OS betweenintermediate- and high-risk MARS pts treated with Ava (200 mg/day starting dose) in the PATHFINDER trialand those treated with BAT in real-world (RW) clinical practice.MethodsData from the PATHFINDER trial (median follow-up: 38.0 months) and a RW retrospective chart reviewstudy (NCT04695431) conducted at six global sites, were used to compare OS between pts treated with 1LAva vs 1L Mido, and 2L+ Ava vs 2L+ BAT, which was predominantly Mido and cladribine (Clad)...Common 2L+ BAT agents included Mido (47.5%), Clad (34.4%), and hydroxyurea (8.2%)...After adjustment, OSwas significantly improved in Ava vs BAT pts (HR [95% CI]: 0.31 [0.13, 0.74]; p=0.008).ConclusionsAmong the combined cohort of MARS intermediate- and high-risk AdvSM pts, avapritinib was associatedwith significantly improved OS compared to midostaurin in the 1L setting and BAT in the 2L+ setting,including in the SM-AHN subgroup. This..."

Clinical • Metastases • Real-world • Real-world evidence • Aggressive Systemic Mastocytosis • Hematological Disorders • Hematological Malignancies • Leukemia • Mast Cell Leukemia • Thrombocytopenia • ASXL1 • RUNX1 • SRSF2

Post-transplant FLT3 inhibitor maintenance is associated with improved survival in FLT3-ITD positive acute myelogenous leukemia irrespective of pre-transplant MRD status (ASH 2025) - "Fourteen (44%) received gilteritinib, 13 (41%) received sorafenib,and 5 (16%) received midostaurin as their first TKI post-HCT. Despite limitations, including limited sample size, we observed an improvement in OS in patients whoreceived post-HCT TKIm, irrespective of pre-HCT MRD status and conditioning regimen intensity.Consistent TKIm post-HCT is challenging due to the high discontinuation rate from toxicity."

Clinical • Post-transplantation • Pre-transplantation • Acute Myelogenous Leukemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Transplantation • FLT3

Mynerva-gimema AML1919 ameliorate Trial: EARLY intensification in FLT3-mutated ACUTE myeloid leukemia based on peripheral blast clearance (ASH 2025) - P3 | "Since 2017, novel agents have receivedapproval for frontline treatment of selected patient categories, changing the uniform management to atargeted diversification of therapeutic approaches: the incorporation of the FLT3 inhibitor Midostaurinfor FLT3-mutated patients, the use of CPX-351 for therapy-related AML and AML with myelodysplasia-related changes, the implementation of Gemtuzumab ozogamicin prominently in patients with favorable-risk cytogenetics...Between April 2020 and June 2025, 28 study sites adhered to the trial and 147 FLT3-mut ptswere enrolled so far. Based on the expected distribution of patients into PBC-high and PBC-low category,a total of 172 subject is to be recruited to include 86 PBC-low patients suitable for randomization to theconventional and experimental arm"

Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • FLT3

Healthcare resource utilization and cost of molecular targeted versus non-targeted therapies in acute myeloid leukemia (ASH 2025) - "We examined AML-related HCRU and costs over a 12-month period following treatment initiation.Patients were categorized into two sub-cohorts: (1) those receiving MTT (ivosidenib, enasidenib,midostaurin, gilteritinib) and (2) biomarker-positive patients (IDH1, IDH2, FLT3) treated only with non-MTT. For AML patients with actionable molecular mutations, treatment with MTTs results inreduced healthcare utilization but increased total costs, primarily due to drug expenses. These findingsemphasize the economic trade-offs in precision oncology and highlight the necessity for strategies toenhance the cost-effectiveness of MTTs in routine care."

HEOR • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • FLT3 • IDH1 • IDH2

A Phase 2 study of sequential administration of gilteritinib after MEC chemotherapy in Relapsed/Refractory FLT3-mutated Acute Myeloid Leukemia in adults: Japan adult leukemia study group (JALSG) RR-FLT3-AML220 study (ASH 2025) - "Introduction: The prognosis of newly diagnosed FLT3-mutated adult acute myeloid leukemia (AML) hasrecently improved by the combination of standard chemotherapy with FLT3 inhibitors, midostaurin orquizartinib...The first cycle was the remission induction treatment that comprised theadministration of MEC (mitoxantrone 8 mg/m2 intravenous infusion, days 1-3; etoposide 100 mg/m2intravenous infusion, days 1-5; cytarabine 100 mg/m2 continuous intravenous infusion, days 1-7) followedby gilteritinib (120 mg/day orally, day 8-28)... Sequential administration of MEC chemotherapy followed by gilteritinib demonstrated highrates of CR and CRc and manageable toxicity in patients with R/R FLT3-mutated AML. The hightherapeutic efficacy of this combination was supported by the high CR rate achieved prior to HSCT.Moreover, the treatment was well tolerated, with no early deaths observed."

Clinical • P2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Thrombocytopenia • FLT3 • NPM1

Ex vivo drug sensitivity testing in Korean AML patients: Integration of functional and genomic profiles for predicting clinical response and survival (ASH 2025) - "Drug responses were highly variable across patients,with dasatinib, venetoclax, gilteritinib, and mitoxantrone showing the greatest inter-patient variability.Genomic stratification revealed established associations: TP53 mutations correlated with multi-agentresistance, while NPM1 and IDH1/2 mutations were associated with increased sensitivity to venetoclax-based combinations...Among ND patients treated withvenetoclax + hypomethylating agents (HMA), ex vivo sensitivity to venetoclax, azacitidine, and decitabineshowed strong correlation with overall survival (OS), with ROC-AUCs of 0.87, 0.67, and 0.87, respectively.Kaplan-Meier survival analysis based on DST-derived risk groups revealed significant differences:Venetoclax (hazard ratio, HR of 9.1, P10.0, P10, P<0.05)...Integration with genomicdata confirmed known drug–mutation relationships and revealed novel sensitivity patterns, includingIDH2–sorafenib and RUNX1–midostaurin. These findings support the incorporation of..."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • ASXL1 • DNMT3A • FLT3 • IDH1 • IDH2 • NPM1 • RUNX1 • TP53

Treatment intensity may alter the prognostic impact of baseline co-mutations in newly diagnosed FLT3-ITD AML treated with FLT3 inhibitor-based therapy (ASH 2025) - " A total of 213 pts were included; 83 received IC + FLT3i [sorafenib in 56 (68%), midostaurin in 1(1%), gilteritinib in 23 (28%), and quizartinib in 3 (4%)] while 130 received LIT + FLT3i [including sorafenibin 32 (25%), midostaurin in 1 (1%), gilteritinib in 48 (37%), and quizartinib in 49 (38%)]. The impact of baseline co-mut on frontline FLT3i-based therapy in ND FLT3-ITD mut AMLmay vary by the nature of the induction regimen. The presence of NPM1 mut +/- epigenetic regulator mutwas associated with improved outcomes with IC + FLT3i, consistent with findings from QuANTUM-1, butimportantly, we noted that co-mut in RAS pathway and MR genes portended a poorer prognosis. Incontrast, co-mut in NPM1 and MR genes did not influence outcomes with LIT + FLT3i regimens (with orwithout VEN)."

Acute Myelogenous Leukemia • Myelodysplastic Syndrome • ASXL1 • DNMT3A • FLT3 • IDH1 • IDH2 • KRAS • NPM1 • NRAS • PTPN11 • RUNX1 • TET2 • WT1

Differences in outcomes with intensive chemotherapy in AML patients according to mutational status – recent real-world results (ASH 2025) - "ELN favorable (fav) and intermediate (int) riskpatients received induction with 7+3 (+ midostaurin for FLT3-mutated pts, and gemtuzumab ozogamicinfor some favorable risk pts)...The OS and RFS for ELN2022 int risk patients treated with IC has improved in recent years and is nowapproaching that of fav risk pts, likely related to the high HSCT rate achievable in int risk patients. ELNadv risk patients continue to have inferior outcomes, even with transplant; however, within this group,RUNX1 mutated patients have a better outcome with IC followed by HSCT than those with other MR genemutations. Revised prognostic scoring systems should take into account this heterogeneity within the advrisk group, as well as more recent outcome data."

Clinical • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • FLT3 • NPM1 • RUNX1 • TP53

Impact of social determinants of health on access to molecular targeted therapy in AML and MDS: A real-world analysis (ASH 2025) - "MTTwas defined as receiving ivosidenib (IDH1), enasidenib (IDH2), or midostaurin/gilteritinib (FLT3) for bothcohorts.We evaluated eleven SDOH domains: unemployment, financial strain, food insecurity, housing instability,interpersonal safety concerns, low educational attainment, mental health disorders, physical inactivity,poor access to care, substance use, and transportation barriers. The modest association betweenfinancial strain and therapy receipt in AML warrants further investigation but was not observed in MDS.These findings suggest that system-level barriers, such as institutional protocols, clinician practices, andpayer dynamics, may play a more substantial role in driving disparities in precision oncology. Futureresearch should prioritize identifying and addressing these structural impediments to promote broadand consistent access to molecular testing and targeted therapies for individuals with myeloidmalignancies."

Clinical • Real-world • Real-world evidence • Acute Myelogenous Leukemia • CNS Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • FLT3 • IDH1 • IDH2 • SF3B1

Risk factor analysis of relapse risk during FLT3-inhibitor post-transplant maintenance therapy following allogeneic hematopoietic stem cell transplantation in Acute Myeloid Leukemia with FLT3-ITD (ASH 2025) - "At HCT, 195 pts (83.7%) were in CR1, 15 (6.4%) in CR2, and 23 (9.9%) beyond CR2(including active disease up to 10% blasts).The most used FLT3i PTM was sorafenib (n=194, 83.3%), followed by gilteritinib (n=50, 21.5%); 1 ptreceived midostaurin. The current study strongly suggests a significantly increased risk of relapse in the group of FLT3-ITD AMLpatients, who do not achieve at least CR2 pre-transplant, have a high DRI or do not develop cGVHD,despite receiving FLT3i PTM. This suggests that those pts should continue FLT3i PTM indefinitely andother methods should be incorporated such as prophylactic DLI within the first 6 months post-transplantto reduce the risk of relapse"

Clinical • Post-transplantation • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Transplantation • ASXL1 • DNMT3A • FLT3 • IDH2 • NPM1 • RUNX1 • TET2 • WT1

Real world outcomes of FLT3 inhibitors and hypomethylating agents as post transplant prophylaxis in Acute Myeloid Leukemia patients transplanted in first complete remission: From the EBMT acute leukemia working party (ASH 2025) - "Several studiesreported promising efficacy and an acceptable safety of post-transplant prophylaxis to prevent suchrelapses, mainly using FLT3 inhibitors (FLT3i), whereas the use of hypomethylating agents (HMA) such asazacitidine (AZA) or decitabine (DEC) remains controversial...Sorafenib was used in 58%, midostaurin in 30%, gilteritinib in 11% while 3 patients receivedsorafenib and midostaurin... This large study further strengthens the role of sorafenib and other FLT3i as standard postHSCT maintenance with 2-year LFS exceeding 80%, not affected by pretransplant use of FLT3i or MRDstatus. Encouraging results were also observed with HMA maintenance, with 2-year LFS exceeding 70%,particularly for patients who had GVHD prior to initiation of maintenance."

Clinical • Post-transplantation • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Transplantation • FLT3 • NPM1

Underexplored mutations in plasma cell myeloma (ASH 2025) - "Many FDA-approved therapies exist in other cancers (such as sotorasib, selumetinib,vemurafenib, enasidenib, midostaurin, ruxolitinib, crizotinib, erlotinib), though these remain largelyunexplored in PCM. CHIP mutation burden in MM / PCM was 40%, Our analysis identified several potentially targetablemutations in pts with PCM, including KRAS, NRAS, BRAF, IDH2, FLT3, JAK2, ALK, and EGFR. Clonalhematopoiesis (CH/CHIP) mutations, such as DNMT3A, TET2, ASXL1, and SRSF2, were also observed.Although the lineage origin of several targetable mutations remains unclear, the likely high plasma cellburden in PCM cases suggests that many may originate within the malignant plasma cell clone. Thishypothesis warrants systematic investigation in future studies."

Tumor mutational burden • Hematological Malignancies • Multiple Myeloma • ALK • ASXL1 • BCOR • BRAF • CALR • CREBBP • CSF3R • DNMT3A • EGFR • FLT3 • GNAS • IDH2 • JAK2 • KRAS • NRAS • PHF6 • PPM1D • PRPF8 • SRSF2 • SUZ12 • TET2 • TMB • TP53

Identification of therapeutic vulnerabilities in FLT3-mutated AML through customized CRISPR screens (ASH 2025) - "FLT3mutations occur in ~30% of AML cases and are targeted by tyrosine kinase inhibitors (TKIs) such asmidostaurin, sorafenib, and gilteritinib across treatment stages. CRISPR/Cas9 screen identified effective genetic modulators of FLT3 inhibitor response inacute myeloid leukemia (AML). These findings reveal critical mechanisms underlying resistance, laying thegroundwork for rational combination therapies to enhance treatment outcomes in FLT3-mutated AML.Future studies will validate these targets using gene knockdown in resistant and sensitive models toevaluate their impact on FLT3 inhibitor response.."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • CDK6 • FASN • FLT3 • NF1 • PTEN • STAT5

Overcoming midostaurin resistance via dual MYC and GSPT1 degradation by the protac GT19715 in FLT3-amplified AML cells (ASH 2025) - "To counteract this, the c-Myc/GSPT1 degrader GT19715 inducedsynergistic cell death in midostaurin-resistant MR cells by suppressing FLT3 expression through GSPT1degradation-mediated SCR. Meanwhile, AKT escape from FLT3 regulation in MR cells under drug selectionpressure may contribute to the development of FLT3-independent resistance."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Targeted Protein Degradation • ATF4 • CASP3 • FLT3 • GSPT1 • MYC • STAT5

Determining sensitivity to FLT3 inhibitors prior to therapy in FLT3 mutant acute myelogenous leukemia (ASH 2025) - "For ex-vivo sensitivity assays, AML cells were treated with several dilutions of a FLT3i(Sorafenib, Midostaurin, Crenolanib, Quizartinib, Gilteritinib, Tuspetinib and MAX-40279 (a dualFLT3/FGFR inhibitor)) and cell viability was assessed with CellTiter-Glo® (Promega). Using our MS-based proteomics measurements and sensitivity results with our proprietary MLmodel, we processed both AML patient samples (N=57) and patient-derived cell lines (N=59), and wewere able to identify 7 distinct clusters. Previously we demonstrated that RPPA proteomics could discriminate FLT3i sensitive andresistant cases and here we present orthogonal confirmation by MS proteomics and ex-vivo sensitivityassays. Moreover, we show that the expression of only three proteins forms a robust biomarker topredict FLT3i sensitivity of FLT3-MUT AML patients prior to therapy. We also identified AML cell lines thatmimic both FLT3i resistance and sensitivity, and combined with deep proteomics data, these..."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • CD34 • FLT3 • PXN • SMARCA2