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Evaluation of time to onset and outcome of cardiac adverse events associated with nilotinib using post-marketing surveillance
CONCLUSIONS: We focused on CAEs caused by nilotinib as post-marketing AEs. Some cases resulted in serious outcomes. Patients should be monitored for signs of onset of these AEs not only at the start of administration, but for a long period of time.PMID:37598671 | DOI:10.1159/000533325 (Source: Oncology)
Source: Oncology - August 20, 2023 Category: Cancer & Oncology Authors: Yuko Kanbayashi Asuka Kojima Haruka Wakabayashi Tadashi Shimizu Mayako Uchida Source Type: research

Cancers, Vol. 15, Pages 4161: A Multicenter Retrospective Chart Review Study of Treatment and Disease Patterns and Clinical Outcomes of Patients with Chronic-Phase Chronic Myeloid Leukemia in Third-Line Treatment or with T315I Mutation
riel Etienne This retrospective chart review study investigated the clinical burden of adult patients with chronic-phase chronic myeloid leukemia (CP-CML) treated at three centers in France (2006&ndash;2021) who failed on two or more tyrosine kinase inhibitors (TKIs; third-line [3L]+ cohort) or harbored the BCR::ABL1 T315I mutation (T315I cohort). In the 3L+ cohort (N = 157; median age at diagnosis, 56 years), TKIs received in 3L (median duration: 17 months) were dasatinib (32%), nilotinib (19%), imatinib (18%), ponatinib (17%), and bosutinib (14%). Of the 145 patients with documented responses in 3L, 42% exper...
Source: Cancers - August 18, 2023 Category: Cancer & Oncology Authors: Franck-Emmanuel Nicolini Fran çoise Huguet Lynn Huynh Churong Xu Christophe Bouvier Aurore Yocolly Gabriel Etienne Tags: Article Source Type: research

Cancers, Vol. 15, Pages 4112: Minimal Residual Disease Detection at RNA and Leukemic Stem Cell (LSC) Levels: Comparison of RT-qPCR, d-PCR and CD26+ Stem Cell Measurements in Chronic Myeloid Leukemia (CML) Patients in Deep Molecular Response (DMR)
Fabritiis Simona Bernardi A Deep Molecular Response (DMR), defined as a BCR::ABL1 transcript at levels &le; 0.01% by RT-qPCR, is the prerequisite for the successful interruption of treatment among patients with Chronic Myeloid Leukemia (CML). However, approximately 50% of patients in Treatment-Free Remission (TFR) studies had to resume therapy after their BCR::ABL1 transcript levels rose above the 0.1% threshold. To improve transcript detection sensitivity and accuracy, transcript levels can be analyzed using digital PCR (dPCR). dPCR increases BCR::ABL1 transcript detection sensitivity 10&ndash;100 fo...
Source: Cancers - August 15, 2023 Category: Cancer & Oncology Authors: Elisabetta Abruzzese Monica Bocchia Malgorzata Monika Trawinska Donatella Raspadori Francesco Bondanini Anna Sicuranza Paola Pacelli Federica Re Alessia Cavalleri Mirko Farina Michele Malagola Domenico Russo Paolo De Fabritiis Simona Bernardi Tags: Communication Source Type: research

Lewy Body Dementia: An Overview of Promising Therapeutics
This article will emphasize potential disease-modifying therapies as well as investigative symptomatic treatments for non-motor symptoms including cognitive impairment and psychosis that can present a tremendous burden to patients with LBD and their caregivers.Recent FindingsWe review 11 prospective disease-modifying therapies (DMT) including four with phase 2 data (neflamapimod, nilotinib, bosutinib, and E2027); four with some limited data in symptomatic populations including phase 1, open-label, registry, or cohort data (vodabatinib, ambroxol, clenbuterol, and terazosin); and three with phase 1 data in healthy population...
Source: Current Neurology and Neuroscience Reports - August 12, 2023 Category: Neuroscience Source Type: research

Real-world experience with ponatinib therapy in chronic phase chronic myeloid leukemia: impact of depth of response on survival and prior exposure to nilotinib on arterial occlusive events
Blood Cancer Journal, Published online: 11 August 2023; doi:10.1038/s41408-023-00891-xReal-world experience with ponatinib therapy in chronic phase chronic myeloid leukemia: impact of depth of response on survival and prior exposure to nilotinib on arterial occlusive events (Source: Blood Cancer Journal)
Source: Blood Cancer Journal - August 11, 2023 Category: Hematology Authors: Maymona G. Abdelmagid Aref Al-Kali Mark R. Litzow Kebede H. Begna William J. Hogan Mirinal S. Patnaik Shahrukh K. Hashmi Michelle A. Elliott Hassan Alkhateeb Omer S. Karrar Farah Fleti Mohammed H. Elnayir Candido E. Rivera Hemant S. Murthy James M. Foran Source Type: research

Association of Nilotinib With Cardiovascular Diseases in Patients With Chronic Myelogenous Leukemia: A National PopulationBased Cohort Study
CONCLUSION: The findings of this study indicate that nilotinib treatment is associated with increased risks of diabetes and hyperlipidemia, with hyperlipidemia being the most significant risk for CVDs. Therefore, we recommend that CML patients receiving nilotinib should undergo screening for diabetes and hyperlipidemia prior to initiating TKI treatment. Additionally, regular monitoring of lipid profiles during TKI therapy and implementing effective management strategies to control hyperlipidemia are crucial.PMID:37561957 | DOI:10.1093/oncolo/oyad225 (Source: The Oncologist)
Source: The Oncologist - August 10, 2023 Category: Cancer & Oncology Authors: Cih-En Huang Kuan-Der Lee Jung-Jung Chang Huey-En Tzeng Shih-Hao Huang Lennex Hsueh-Lin Yu Min-Chi Chen Source Type: research

Fluid retention-associated adverse events in patients treated with BCR::ABL1 inhibitors based on FDA Adverse Event Reporting System (FAERS): a retrospective pharmacovigilance study
Conclusions This pharmacovigilance study serves as a clinical reminder to physicians to be more vigilant for fluid retention-associated AEs with BCR::ABL inhibitors. (Source: BMJ Open)
Source: BMJ Open - August 3, 2023 Category: General Medicine Authors: Huang, J., Cai, J., Ye, Q., Jiang, Q., Lin, H., Wu, L. Tags: Open access, Pharmacology and therapeutics Source Type: research

Vodobatinib, a potent, orally bioavailable brain-penetrating inhibitor of c-Abl as a potential neuroprotective agent for treatment of Parkinson disease
Background:Preclinical evidence suggests that c-Abl is critical for pathogenesis of Parkinson Disease (PD). Vodobatinib is a potent, orally bioavailable inhibitor of c-Abl currently being evaluated in patients with PD in the PROSEEK clinical trial. Nilotinib, a multikinase inhibitor of c-Abl, was recently shown to be unsuccessful in slowing PD progression (Simuni et al. 2021). This failure of nilotinib at its maximally permissible dose of 300mg was attributed to insufficient brain penetration because the concentration of nilotinib in the CSF was found to be 7-fold lower than its IC50 for c-Abl. (Source: Parkinsonism and Related Disorders)
Source: Parkinsonism and Related Disorders - August 1, 2023 Category: Neurology Authors: R.R. Walsh, S.P. Piccoli, R.S. Talluri, S. Mandhane, D. Love, O. Hurko, S.-L. Yao, V. Ramanathan, N. Damle Source Type: research

Cuproptosis-related signature for clinical prognosis and immunotherapy sensitivity in hepatocellular carcinoma
ConclusionsOur findings highlight the potential of the CRGs risk score as an independent and promising biomarker for clinical prognosis and immunotherapy sensitivity in HCC patients. (Source: Journal of Cancer Research and Clinical Oncology)
Source: Journal of Cancer Research and Clinical Oncology - July 11, 2023 Category: Cancer & Oncology Source Type: research

Evaluation of chronic drug-induced electrophysiological and cytotoxic effects using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs)
In conclusion, the evaluation of chronic drug-induced cardiotoxicity using a hiPSC-CMs in vitro assay can contribute to the early de-risking of compounds and help optimize the drug development process. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - July 10, 2023 Category: Drugs & Pharmacology Source Type: research

Myelofibrosis at diagnosis is associated with the failure of treatment-free remission in CML patients
In this study, we show that presence of myelofibrosis (MF) at the time of diagnosis is a factor associating with TFR failure. Fibrotic transformation is governed by the action of several cytokines, and interestingly, some of them have also been described to support LSC persistence. At the cellular level, these could be produced by both malignant cells and by components of the bone marrow (BM) niche, including megakaryocytes (MKs) and mesenchymal stromal cells (MSCs). In our cohort of 57 patients, around 40% presented with MF at diagnosis and the number of blasts in the peripheral blood and BM was significantly elevated in ...
Source: Frontiers in Pharmacology - July 4, 2023 Category: Drugs & Pharmacology Source Type: research