A5015789771- Chronic Myeloid Leukemia Treatments
- Chronic Lymphocytic Leukemia Research
- Eosinophilic Disorders and Syndromes
- Acute Lymphoblastic Leukemia research
- Click Chemistry and Applications
- HER2/EGFR in Cancer Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Lung Cancer Treatments and Mutations
- Lymphoma Diagnosis and Treatment
- Acute Myeloid Leukemia Research
- Quinazolinone synthesis and applications
- Mast cells and histamine
- Chemotherapy-induced cardiotoxicity and mitigation
- Fungal Plant Pathogen Control
- HIV/AIDS drug development and treatment
- Glycosylation and Glycoproteins Research
- Gastrointestinal Tumor Research and Treatment
- PI3K/AKT/mTOR signaling in cancer
- Synthesis of Tetrazole Derivatives
- Multiple Myeloma Research and Treatments
- CNS Lymphoma Diagnosis and Treatment
- Kruppel-like factors research
- Monoclonal and Polyclonal Antibodies Research
- Peptidase Inhibition and Analysis
- Advanced Breast Cancer Therapies
Memorial Sloan Kettering Cancer Center
2016-2025
Center for Discovery
2024
Hackensack Meridian Health
2024
Kettering University
2015-2024
Federal Almazov North-West Medical Research Centre
2023
Tashkent Pediatric Medical Institute
2023
Imperial College London
2023
Cornell University
2000-2020
Weill Cornell Medicine
2020
Medizinische Hochschule Hannover
2019
Resistance to tyrosine kinase inhibitors in patients with chronic myeloid leukemia (CML) and Philadelphia chromosome–positive acute lymphoblastic (Ph-positive ALL) is frequently caused by mutations the BCR-ABL domain. Ponatinib (AP24534) a potent oral inhibitor that blocks native mutated BCR-ABL, including gatekeeper mutant T315I, which uniformly resistant inhibitors.
Purpose Bosutinib is a potent dual SRC/ABL kinase inhibitor approved for adults with Philadelphia chromosome–positive chronic myeloid leukemia (CML) resistant and /or intolerant to prior therapy. We assessed the efficacy safety of bosutinib versus imatinib first-line treatment chronic-phase CML. Methods In this ongoing, multinational, phase III study, 536 patients newly diagnosed CML were randomly assigned 1:1 receive 400 mg once daily (n = 268) or 268). Per protocol, was in who typical...
Advanced systemic mastocytosis comprises rare hematologic neoplasms that are associated with a poor prognosis and lack effective treatment options. The multikinase inhibitor midostaurin inhibits KIT D816V, primary driver of disease pathogenesis. We conducted an open-label study oral at dose 100 mg twice daily in 116 patients, whom 89 mastocytosis-related organ damage were eligible for inclusion the efficacy population; 16 had aggressive mastocytosis, 57 neoplasm, mast-cell leukemia. outcome...
Asciminib is an allosteric inhibitor that binds a myristoyl site of the BCR-ABL1 protein, locking into inactive conformation through mechanism distinct from those for all other ABL kinase inhibitors. targets both native and mutated BCR-ABL1, including gatekeeper T315I mutant. The safety antileukemic activity asciminib in patients with Philadelphia chromosome-positive leukemia are unknown.
This analysis from the multicenter, open-label, phase 3 BFORE trial reports efficacy and safety of bosutinib in patients with newly diagnosed chronic (CP) myeloid leukemia (CML) after five years' follow-up. Patients were randomized to 400-mg once-daily (n = 268) or imatinib 268; three untreated). At study completion, 59.7% bosutinib- 58.1% imatinib-treated remained on treatment. Median duration treatment time was 55 months both groups. Cumulative major molecular response (MMR) rate by 5...
Asciminib, the first BCR::ABL1 inhibitor that Specifically Targets ABL Myristoyl Pocket (STAMP), is approved worldwide for treatment of adults with Philadelphia chromosome-positive chronic myeloid leukemia in phase (CML-CP) treated ≥2 prior tyrosine kinase inhibitors (TKIs). In ASCEMBL, patients CML-CP TKIs were randomized (stratified by baseline major cytogenetic response [MCyR]) 2:1 to asciminib 40 mg twice daily or bosutinib 500 once daily. Consistent previously published primary analysis...
Abstract Asciminib targets the BCR::ABL1 myristoyl pocket, maintaining activity against T315I , which is resistant to most approved adenosine triphosphate–competitive tyrosine kinase inhibitors. We report updated phase I results (NCT02081378) assessing safety/tolerability and antileukemic of asciminib monotherapy 200 mg twice daily in 48 heavily pretreated patients with T315I-mutated chronic-phase chronic myeloid leukemia (CML-CP; data cutoff: January 6, 2021). With 2 years’ median exposure,...
STI571 exemplifies the successful development of a rationally designed, molecularly targeted therapy for treatment specific cancer. This article reviews identification Bcr-Abl as therapeutic target in chronic myelogenous leukemia and steps an agent to specifically inactivate this abnormality. Issues related clinical trials agents are discussed, including dose selection, optimizing therapy, predicting response, possible mechanisms resistance STI571. Lastly, potential use other malignancies...
Treatment-free remission (TFR) in patients with chronic myeloid leukemia phase (CML-CP) is considered a feasible option, especially the ability of second-generation tyrosine kinase inhibitors to induce higher rates sustained deep molecular response (DMR). DASFREE an open-label, single-arm, multicenter II trial assessing TFR after dasatinib discontinuation CML-CP (N = 84). At 2 years, was 46% all patients. Multivariate analyses revealed statistically significant associations between 2-year...
BACKGROUND Effective treatment options for patients with chronic myeloid leukemia (CML) or Philadelphia‐positive (Ph+) acute lymphoblastic (ALL) who have the threonine to isoleucine mutation at codon 315 (T315I) are few. The objective of this study was compare overall survival (OS) between CML and those Ph+ ALL received ponatinib versus allogeneic stem cell transplantation (allo‐SCT). METHODS A post hoc, retrospective, indirect comparison OS among single‐agent in Ponatinib Evaluation (PACE)...
Vascular and cardiac safety during tyrosine kinase inhibitor (TKI) therapy is an emerging issue. We evaluated vascular/cardiac toxicities associated with long-term bosutinib treatment for Philadelphia chromosome-positive (Ph+) leukemia based on treatment-emergent adverse events (TEAEs) changes in QTc intervals ejection fraction two studies: a phase 1/2 study of second-/third-/fourth-line Ph+ resistant/intolerant to prior TKIs (N = 570) 3 first-line (n 248) versus imatinib 251) chronic...
<h3>Importance</h3> Tyrosine kinase inhibitors (TKIs) have been associated with improved survival of patients chronic myeloid leukemia (CML) but are also adverse effects, especially fatigue and diarrhea. Discontinuation TKIs is safe the successful achievement treatment-free remission (TFR) for some patients. <h3>Objective</h3> To evaluate molecular recurrence (MRec) patient-reported outcomes (PROs) after TKI discontinuation US CML. <h3>Design, Setting, Participants</h3> The Life After...
Abstract Background The phase 2 PACE (Ponatinib Ph+ ALL and CML Evaluation) trial of ponatinib showed robust long-term benefit in relapsed Philadelphia chromosome-positive (Ph+) leukemia; arterial occlusive events (AOEs) occurred ≥ 25% patients based on investigator reporting. However, AOE rates vary depending the definitions reporting approach used. Methods To better understand clinically relevant AOEs with ponatinib, an independent cardiovascular adjudication committee reviewed 5-year data...
Abstract Asciminib is approved for patients with Philadelphia chromosome–positive chronic-phase chronic myeloid leukemia (CML-CP) who received ≥2 prior tyrosine kinase inhibitors or have the T315I mutation. We report updated results of a phase 1, open-label, nonrandomized trial (NCT02081378) assessing safety, tolerability, and antileukemic activity asciminib monotherapy 10–200 mg once twice daily in 115 CML-CP without (data cutoff: January 6, 2021). After ≈4-year median exposure, 69.6%...
Ponatinib, the only approved all known-BCR::ABL1 inhibitor, is a third-generation tyrosine-kinase inhibitor (TKI) designed to inhibit BCR::ABL1 with or without any single resistance mutation, including T315I, and induced robust durable responses at 45 mg/day in patients CP-CML resistant second-generation TKIs PACE trial. However, cardiovascular toxicities, arterial occlusive events (AOEs), have emerged as treatment-related AEs within this class of TKIs. The OPTIC trial evaluated efficacy...