midostaurin / Generic mfg. - LARVOL DELTA

Cheminformatic identification of small molecules targeting acute myeloid leukemia. (PubMed, bioRxiv) - "Structurally-unrelated compounds from different clusters caused the same phenotype, validating our structure-blind screening approach. Furthermore, strong synergy between these compounds and the AML treatment midostaurin underscores their therapeutic potential."

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

New treatments for systemic mastocytosis in 2025. (PubMed, Curr Opin Allergy Clin Immunol) - "Despite the considerable therapeutic progress in recent years, systemic mastocytosis is an incurable disease. In the last 20 years, the management of systemic mastocytosis has transformed from a one-size-fits-all approach, characterized by nonspecific cytoreductive drugs, to a tailored strategy focused on increasingly precise molecular targets, with the most notable example being the KIT inhibitors. Recently, the FDA and EMA have approved two drugs for treating systemic mastocytosis: avapritinib and midostaurin. Moreover, numerous trials are currently assessing the efficacy of new molecules: most are testing new-generation KIT inhibitors (ripretinib, bezuclastinib, elenestinib, masitinib, nintedanib), others focusing on Bruton's kinase (TL-895), interleukin-6 (sarilumab), sialic acid-binding immunoglobulin-like lectin-8 (lirentelimab), mTOR and CD33, among others. Real-life data are needed to confirm preliminary preclinical results."

Journal • Aggressive Systemic Mastocytosis • CD33 • IL6

Real-world adherence and tolerability of FLT3 inhibitors as post-allogeneic transplant maintenance therapy in older adults with AML: A Medicare claims data cohort study. (ASCO 2025) - " An observational cohort study assessed healthcare resource utilization (HRU), treatment adherence (proportion of days covered [PDC]), and dose modifications among patients with AML who received alloHCT with FLT3-TKI (gilteritinib, midostaurin or sorafenib) maintenance therapy. Real-world treatment patterns suggest gilteritinib maintenance is well-tolerated among older adult alloHCT recipients with AML. While the low sample size limits interpretability of some study results, gilteritinib may be associated with improved adherence and tolerability relative to other FLT3-TKIs."

Adherence • Clinical • HEOR • Medicare • Real-world • Real-world evidence • Reimbursement • US reimbursement • Acute Myelogenous Leukemia • Transplantation

Retrospective study of antimicrobial prophylaxis and infections in patients with acute myeloid leukemia. (ASCO 2025) - "The most common induction therapies were 7 + 3 (63.5%), azacitidine (11.1%), azacitidine + venetoclax (6.3%), and 7 + 3 + midostaurin (4.8%). 55/63 (87.3%) patients received fungal prophylaxis, usually posaconazole (n = 47)...47/63 (74.6%) patients received viral prophylaxis with acyclovir or valacyclovir... In this single-center retrospective study, fungal and viral prophylaxis were used in most patients, whereas bacterial prophylaxis was rare. Bacterial infections were frequently encountered with a high rate of bacteremia. Aspergillus was the most common fungal pathogen, reinforcing the importance of mold-active fungal prophylaxis."

Retrospective data • Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Novel Coronavirus Disease • Oncology • Pneumonia • Respiratory Diseases

Real-world clinical characteristics and outcomes of systemic mastocytosis (SM) patients (Pts) in the era of targeted treatments (Txs): A single-center cohort analysis. (ASCO 2025) - "89% ISM pts were on active surveillance (AS) for first line (1L) tx, and 87% were on avapritinib (ava) for 2L tx...With ASM pts, 45% were on ava, 27% AS, and 9.1% each for imatinib, midostaurin (mido) and other for 1L... This real-world study highlights the heterogeneity in SM pts. OS was NR for ISM consistent with prior data. OS for ASM pts was NR; previously OS was reported at 3.5 years."

Clinical • Real-world • Real-world evidence • Aggressive Systemic Mastocytosis • Chronic Myelomonocytic Leukemia • Fatigue • Hematological Malignancies • Leukemia • Mast Cell Leukemia • Multiple Myeloma • Oncology • Pain • Smoldering Multiple Myeloma • KIT

Outcomes for adults with KMT2A-r acute myeloid leukemia treated with venetoclax plus azacitidine (Ven/Aza) or intensive chemotherapy (IC): A single-center retrospective study. (ASCO 2025) - "Funded by No funding sources reported Background: KMT2A-rearranged acute myeloid leukemia (KMT2A-r AML) is known for adverse outcomes due to aggressive disease presentation and high relapse rates. Our results demonstrate that KMT2A-r is associated with a monocytic phenotype and highlights poor outcomes in KMT2A-r AML when treated with Ven/Aza as frontline therapy. Allo-HSCT independently improves the likelihood for long term survival. Whether the addition of a menin inhibitor to frontline chemotherapy will improve outcomes is being assessed in multiple clinical trials."

Retrospective data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • CD14 • ITGAM • ITGAX • KMT2A

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

The Multi-kinase Inhibitor Midostaurin Mitigates Loss of Intercellular Adhesion and Skin Blistering in Pemphigus Vulgaris. (PubMed, J Invest Dermatol) - "Ultrastructural analyses revealed that midostaurin restored the integrity of desmosomes. These findings indicate that midostaurin can counteract the pathogenic effects of pemphigus autoantibodies, suggesting its potential as a therapeutic agent for pemphigus."

Journal • Dermatology • Immunology • Oncology • Pemphigus Vulgaris • FLT3

Characteristics and Therapeutic Strategies for Diffuse Cutaneous Mastocytosis. (PubMed, JAMA Dermatol) - "Seven patients (21.2%) received early systemic treatment (imatinib, midostaurin, or sirolimus depending on the type of KIT variants), starting at a mean (SD) age of 80.8 (135.6) months and continuing for a mean (SD) of 4.0 (2.6) years, with generally good tolerance and efficacy. In this cohort study, DCM presentation differs significantly from MPCM, with a higher risk of anaphylaxis and aggressive systemic forms, the latter being consistently associated with the KIT D816V variant. Tyrosine kinase inhibitors and sirolimus were generally effective and well tolerated in this pediatric population, with the choice of treatment depending on the type of KIT variants."

Journal • Aggressive Systemic Mastocytosis • Pediatrics • Rare Diseases

Preclinical validation of PKC412 as a therapy candidate for epidermolysis bullosa simplex across multiple keratin pathogenic variants. (PubMed, Br J Dermatol) - "PKC412 markedly enhanced intercellular cohesion and stress resilience in patient-derived EBS keratinocytes, both in monolayer and 3D culture systems. These findings highlight PKC412 as a promising therapeutic candidate for the treatment of EBS."

Journal • Preclinical • KRT14 • KRT5

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

NCI-2014-01103: Cladribine, Idarubicin, Cytarabine, and Venetoclax in Treating Patients With Acute Myeloid Leukemia, High-Risk Myelodysplastic Syndrome, or Blastic Phase Chronic Myeloid Leukemia (clinicaltrials.gov) - P2 | N=508 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: May 2026 ➔ May 2030 | Trial primary completion date: May 2025 ➔ May 2030

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

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 Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Targeted Protein Degradation • ABL1 • BCR • FLT3 • IDH1 • NPM1

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

VEN-BASED SCHEMES, ARE THEY BETTER THAN '3 + 7'? (EHA 2025) - "Hypomethylating agents (HMAs) in combination with venetoclax (HMA-Ven) have emerged as a less intensive alternative with promising efficacy and a more favorable safety profile. Aims: This study aimed to compare the efficacy and safety of "3+7" (+/- gemtuzumab ozagamicin or midostaurine) and HMA-Ven... HMA-Ven is non-inferior to "3+7" in terms of OS and PFS in AML, with a significantly lower incidence of FN and IFD. These findings suggest that HMA-Ven could be a preferred treatment option for AML, balancing efficacy with a better safety profile."

Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology

RISK FACTORS AND MANAGEMENT OF PERIANAL INFECTIONS IN ACUTE LEUKEMIA PATIENTS (EHA 2025) - "Most used HDCT regimen was "7+3" or "7+3+midostaurin" (51%)... Perianal infections are rare but potentially life-threatening in HDCT treated AL patients. This analysis underscores the importance of detailed medical history, close monitoring of at-risk patients, a multidisciplinary approach and needs to be validated in larger prospective trials."

Clinical • Diabetes • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Metabolic Disorders • Neutropenia • Obesity • Oncology • Septic Shock

IMPACT OF INDIVIDUALIZED DOSING PROFILES OF MIDOSTAURIN ON SAFETY, RESPONSE AND SURVIVAL IN PATIENTS WITH ADVANCED SYSTEMIC MASTOCYTOSIS (EHA 2025) - "In pts with AdvSM, midostaurin demonstrated a favorable safety profile with durable responses being achieved at all dosing regimens between 50 and 100 mg BID. Physicians and pts should be aware of a potential discontinuation syndrome which can be prevented by dose tapering and systemic corticosteroids."

Clinical • Metastases • Fatigue • Hematological Disorders • Neutropenia • Oncology • Respiratory Diseases • CRP

SOLUBLE ST2 AS A POTENTIAL BIOMARKER AND THERAPEUTIC TARGET IN SYSTEMIC MASTOCYTOSIS (EHA 2025) - "Over 90% of patients with mastocytosis bear an activating mutation in the KIT gene at codon 816 (most commonly KIT D816V), which leads to autonomous MC proliferation.Although treatment options for patients with mastocytosis have increased in recent years, especially with the approval of the KIT-targeting tyrosine kinase inhibitors midostaurin and avapritinib, many patients are still lacking an adequate response, and additional therapies are needed. Taken together, our study shows that serum ST2 levels, particularly the soluble isoform, are significantly increased in SM patients compared to healthy controls, especially in advSM patients. This suggests that ST2 may play a role in the pathophysiology of SM and could potentially serve as a biomarker of disease severity as well as a therapeutic target in SM."

Biomarker • IO biomarker • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • IL33 • IL6 • PD-L1 • TSLP

THERAPEUTIC STRATEGIES TARGETING SRSF2 AND KIT MUTATIONS IN SYSTEMIC MASTOCYTOSIS (EHA 2025) - "The efficacy of KIT TKIs midostaurin and avapritinib, and the synergistic effects of spliceosome inhibitors MS023, RKI-1447, and CTX-712 were also evaluated. Our findings suggest that combining KIT TKIs with spliceosome inhibitors represents a promising therapeutic approach for SM. The study highlights the role of SRSF2 and KIT mutations in driving MC malignancy and emphasizes the potential of targeting the spliceosome machinery to overcome drug resistance, potentially improving treatment outcomes for advanced SM."

Oncology • KIT • SRSF2 • STAT5

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 • Gastrointestinal Disorder • Musculoskeletal Pain • Neutropenia • Thrombocytopenia • FLT3

THE IMPACT OF MEASURABLE RESIDUAL DISEASE ON OUTCOMES IN PATIENTS WITH FLT3-ITD MUTATED ACUTE MYELOID LEUKEMIA (EHA 2025) - "Various types of induction therapies were used such as 7+3 (cytarabine/anthracycline) or CPX-351 +/- midostaurin +/- gemtuzamab... Our findings highlight the importance of highly sensitive FLT3-ITD MRD testing and its associated prognostic impact for pts with FLT3-ITD mutated AML after achieving response. Pts with undetectable MRD have significantly longer survival. For detectable MRD, HCT remains an important treatment modality to extend survival."

Clinical • Residual disease • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • DNMT3A • FLT3 • IDH2 • NPM1 • RUNX1 • TET2 • WT1

NOT ALL FLT3-MUTATED ACUTE MYELOID LEUKEMIAS ARE OF INTERMEDIATE RISK IN THE ERA OF FLT3 INHIBITORS (EHA 2025) - "We analyze patients included in the MDA-AML-2018-06 study which included 215 FLT3 mut AML patients from 27 Spanish sites treated with midostaurin plus intensive chemotherapy (Midos+IC).A total of 215 (116 female) patients were analyzed, median age 53 (18-76), 138pt =0.5) 101pt... Based on our experience the ELN 2017 risk stratification remains valid for predicting OS in FLT3 mut AML patients treated with Midos plus IC and could also be useful for treatment decisions after achieving a CRc."

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

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

LONG-TERM REAL-WORLD EXPERIENCE WITH CPX-351 TREATMENT FOR ACUTE MYELOID LEUKEMIA IN ENGLAND (EHA 2025) - "Twenty-four (4%) patients received azacitidine for prior malignancy; no patients received midostaurin in combination with CPX-351... This is the largest RW evidence study of CPX-351 to date, complementing the 5-year follow-up data from the pivotal phase 3 trial that supported its regulatory approval. OS in patients aged ≥60 years was comparable to the phase 3 trial, including patients aged ≥70 years. Additionally, the findings help address the gap in CPX-351 outcomes data for patients <60 years; in this patient group OS was favorable."

Clinical • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

COPY NEUTRAL LOH OF KITLG GENE IS ASSOCIATED WITH A LOWER REMISSION RATE IN PATIENTS WITH ACUTE MYELOID LEUKEMIA. (EHA 2025) - "Midostaurin was added for patients with FLT3-ITD mutation, except for one comorbid patient... KITLG gene cn-LOH might be associated with a lower response to therapy in AML."

Clinical • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • FGFR3 • FLT3 • KMT2A • SATB1