midostaurin

We analyzed 523 adults with FLT3-ITD AML in first complete remission who underwent allo-HCT between 2011 and 2023 in 13 German transplant centers participating in the national DRST registry; 22% received FLT3i maintenance (sorafenib 49%, midostaurin 37%, gilteritinib 5%, unknown 9%). Sorafenib maintenance (n=50) demonstrated superior efficacy with 5-year OS of 85% versus 62% (HR 2.979, p=0.0045) and RFS of 84% versus 55% (HR 2.771, p=0.0043) compared to no maintenance. These real-world findings, while limited by the retrospective design and potential selection bias, align with randomized trial data and support the use of FLT3i maintenance as part of post-transplant care for FLT3-ITD AML.

Currently, most leukemias are effectively treated with immunotherapies (highly effective monoclonal antibodies targeting CD19 [blinatumomab], or CD22 [inotuzumab ozogamicin]), BCR::ABL1 tyrosine kinase inhibitors (TKIs; e.g., dasatinib, ponatinib), Bruton TKIs (e.g., ibrutinib, acalabrutinib), BCL-2 inhibitors (venetoclax), IDH1/2 inhibitors (ivosidenib, olutasidenib, and enasidenib), FLT3 inhibitors (e.g., midostaurin, quizartinib, and gilteritinib), menin inhibitors (revumenib, ziftomenib), and chimeric antigen receptor T-cell therapies. Herein, we provide a high-level overview of prominent clinical developments across all leukemias. In contemporary times, harnessing the benefits of novel targeted therapies and the evolving treatment landscape bolster the optimistic view that most, if not all, leukemias are curable.

Targeted therapies have improved outcomes in molecularly defined subsets of AML, with menin, IDH and FLT3 inhibitors representing major advances. However, TP53-mutated AML continues to carry a dismal prognosis, underscoring the need for more effective therapeutic strategies. Continued biomarker-driven research, novel drug combinations, and mechanistic insights will be essential to further refine AML treatment and improve long-term survival across disease subsets.

Drug sensitivity analysis showed positive correlations between the risk score and IC50 values of paclitaxel and rapamycin, and a negative correlation with midostaurin. In vitro assays demonstrated that HMGN1 inhibition significantly suppressed SiHa and HeLa cell proliferation and induced S-phase arrest, highlighting its potential as a therapeutic target. In conclusion, this study developed a reliable LAG-based prognostic model and uncovered key lactylation-related mechanisms in cervical cancer, providing new insights for biomarker discovery and personalized therapeutic strategies.

P2/3, N=230, Not yet recruiting, European Organisation for Research and Treatment of Cancer - EORTC

FLT3 inhibitors - midostaurin (first-generation), gilteritinib and quizartinib (second-generation) - have been developed to block FLT3 activation. The only exception was an higher risk of ALT increased with gilteritinib (RR = 2.40, 95% CI: 1.16-4.95). Future studies should stratify safety outcomes by demographic and clinical characteristics and incorporate long-term follow-up for a more comprehensive safety assessment in clinical practice.

Indeed, the use of selective BCL-2 antagonists (e.g. venetoclax) and FLT3 inhibitors (e.g. midostaurin, gilteritinib) which target specific molecular characteristics of leukaemic cells, has enhanced outcomes and survival rates...Spurred on by the recent FDA approval of revumenib, menin inhibitors hold the potential to further shift the treatment paradigm for this patient population. Here, we aim to provide a comprehensive overview of the pathogenesis of KMT2A rearrangements, with a focus on KMT2A fusion genes and proteins within paediatric AML patients. Additionally, we summarise the challenges arising from resistance to menin inhibitors, and we touch on the potential of combination therapies to expand the efficacy of menin inhibition and mitigate some of the resistance mechanisms employed by leukaemic clones.

These benefits were confirmed by propensity score matching. This large real-world study demonstrates that combining midostaurin with IC significantly improves remission rates and survival outcomes in elderly patients with FLT3-mutated AML, supporting its consideration in this population.

Percentage cost variation ranged from 8% (Bosutinib) to 14,774.74% (Midostaurin), with corresponding cost ratios up to 148.75...Absolute savings versus median branded costs ranged from ₹2,968 (Dasatinib) to ₹25,270 (Lapatinib), while percentage savings ranged from 58.89% (Dasatinib) to 91.32% (Imatinib)...However, limited PMBJP coverage restricts their overall benefit. Expanding Janaushadhi availability, improving price regulation, and encouraging rational prescribing are crucial to ensure equitable access to targeted cancer therapies in India.

Five patients (8.8%) were refractory to induction therapy, and relapse occurred in 21.1% (12 patients). These findings support the effectiveness and acceptable tolerability of midostaurin in routine clinical practice for FLT3-mutated AML.

By targeting nucleic acids, FLT3 or CD33, several FDA-approved NPs and NPDs (i.e., cytarabine, anthracyclines, midostaurin, melphalan and calicheamicin linked to anti-CD33) are the major agents of upfront treatment of AML. This review summarizes the current state of the art, and provides a summary of selected NPs/NPDs which are either entering or have been investigated in preclinical and clinical trials, alone or in combination with current chemotherapy. With multifaceted actions, these biomolecules may target all hallmarks of AML, including multidrug resistance and deregulated metabolism.

Midostaurin, a clinical PKC/FLT3 inhibitor used in FLT3-ITD-positive AML, potently re-sensitized ImR cells to imatinib. Our findings suggest that targeting LIN28A and its downstream effectors, particularly PKC, could overcome resistance to imatinib and next-generation BCR-ABL inhibitors.