midostaurin

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.

Our results show that GO can safely be combined with intensive chemotherapy with midostaurin in ND, FLT3-mutated AML. This trial was registered at www.clinicaltrials.gov as #NCT03900949.

Initial treatment with hydroxyurea and leukapheresis followed by azacitidine and venetoclax resulted in an inadequate treatment response. Given the lack of research on the FLT3 V491L mutation, we conducted an ex vivo sensitivity study using the patient's diagnostic bone marrow blasts to assess and compare the anti-leukemic efficacy of midostaurin, quizartinib, and gilteritinib...Treatment of relapsed AML with a non-canonical mutation is challenging due to the lack of data regarding FLT3 inhibitors. This case highlights the potential role of gilteritinib in targeting the rare FLT3 V491L mutation, underscoring the need for further research and improved accessibility to effective therapies.

The present study aimed to evaluate the impact, challenges, and outcome by adding bortezomib to the FLAG (fludarabine, cytarabine, and filgrastim) regimen in these populations in a resource-constraint setting...Sorafenib ( n  = 1) and midostaurin ( n  = 2) were given along with chemotherapy for children with FLT3 mutations...At the last follow-up, three (23.08%) patients are alive. FLAG-bortezomib regimen could help in pediatric and adolescent relapsed AML to achieve a remission comparable with other regimen in low- and middle-income countries, highlighting its potential.

Notably, 47% of patients received previous midostaurin. AdvSM subtype, the presence and number of additional comutated genes beyond KIT D816V, BM mast cell burden, and KIT D816V variant allele fraction were associated with the presence and/or number of WHO/mIWG organ damage findings. Our study provides a snapshot of the correlates of organ damage in patients enrolled in clinical trials of avapritinib and identifies a key association between molecular profile and burden of organ damage.

In this review, we summarize the human myeloid leukemia cell lines that express mutated FLT3 and the effect of several drugs on these cell lines. Our aim in this review is to provide clinicians with a basic science understanding of human myeloid leukemia cell lines and to provide scientific researchers with the clinical implications of FLT3 signaling inhibition.

Here, we applied our recently developed single-cell lineage tracing method ReSisTrace to identify cells that are intrinsically resistant or sensitive to the FLT3 inhibitors midostaurin and quizartinib in AML with FLT3-ITD mutations...In addition, in an FLT3-ITD-positive AML patient-derived xenograft (PDX) mouse model, the CC-90009 and quizartinib combination showed significantly higher anti-tumor efficacy and prolonged overall survival compared to either treatment alone...Vistusertib (mTOR inhibitor), linsitinib (IGF1R and insulin receptor inhibitor), and meisoindigo (IGF1R and Src family kinase inhibitor), all inhibiting pathways parallel to or downstream of oncogenic FLT3 signaling, were predicted and validated to sensitize FLT3-mutated cell lines and primary cells to FLT3 inhibitors. Collectively, these findings demonstrate the ability of ReSisTrace to unveil pre-existing transcriptional features of treatment vulnerability in hematological cancers and elucidate strategies for enhancing FLT3 inhibitor treatment efficacy in FLT3-ITD-mutated AML.

Our study confirms NPM1 mutations independently predict improved survival in pediatric AML, though outcomes remain inferior to those reported from high income countries. Larger studies are needed in pediatric AML due to its rare occurrence.