Asciminib in chronic myeloid leukemia: many questions still remain to be answered

Eşkazan, Ahmet Emre

doi:10.1038/s41408-021-00475-7

Cited by 4 publications

(2 citation statements)

References 11 publications

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“…Only a single study reporting HRQOL assessment in a third-line setting in CML was identified in the literature, in which the symptom of fatigue was identified as the most important independent predictor of health utility; however, the use of different PRO assessments in the study makes the comparison of findings challenging [ 27 ]. Finally, comparisons of asciminib with other practical treatment options for patients with resistant/intolerant CML-CP, such as ponatinib or allogeneic hematopoietic stem cell transplantation, should be evaluated in future studies to better understand the treatment benefit of asciminib in the real-life setting [ 28 ]. The inclusion of PRO assessments in routine clinical practice is also important for understanding patient care and treatment burden in the real world [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

Health-related quality of life of patients with resistant/intolerant chronic phase chronic myeloid leukemia treated with asciminib or bosutinib in the phase 3 ASCEMBL trial

et al. 2023

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In ASCEMBL, an open-label, randomized Phase 3 study, asciminib demonstrated superior efficacy and better safety profile compared with bosutinib in patients with chronic myeloid leukemia in chronic phase (CML-CP) previously treated with ≥2 tyrosine kinase inhibitors. Health-related quality of life (HRQOL) reported by patients is key to understanding the benefit and impact of treatment on patients’ lives, and is becoming increasingly important as the life expectancy of CML-CP patients increases and patients require long-term treatment. In ASCEMBL, patients completed questionnaires to assess CML symptoms and interference with daily life (M.D. Anderson Symptom Inventory – CML [MDASI-CML]), general HRQOL (five-level EQ-5D [EQ-5D-5L], Patient Global Impression of Change – CML [PGIC-CML]), and impact of CML on working life and activity (Work Productivity and Activity Impairment questionnaire – CML [WPAI-CML]). Patients’ CML symptoms and HRQOL remained stable during 48 weeks of treatment with asciminib, with a general trend for decreased CML symptom severity, particularly for fatigue, and improvement in HRQOL. A clinically meaningful increase in diarrhea severity was observed in patients treated with bosutinib compared to asciminib. These data provide better understanding of the patient perspective and treatment impact on HRQOL in a later-line setting, where little information has been published to date.

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Section: Discussionmentioning

confidence: 99%

Health-related quality of life of patients with resistant/intolerant chronic phase chronic myeloid leukemia treated with asciminib or bosutinib in the phase 3 ASCEMBL trial

et al. 2023

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“…The three-dimensional binding mode of these fragments is explored by determining the structure of the fragment-bound target using X-ray crystallography, NMR spectroscopy or cryoelectron microscopy, and guided by these structures the fragments are chemically “grown” or “linked” to form a larger molecule with higher affinity and drug-like properties. Over the past 20 years, FBDD has achieved significant success by delivering six FDA approved drugs namely, vemurafenib ( Bollag et al, 2012 ), venetoclax ( Souers et al, 2013 ), erdafitinib ( Perera et al, 2017 ), pexidartinib ( Tap et al, 2015 ), sotoracib ( Blair, 2021 ) and Asciminib ( Eşkazan, 2021 ) ( Table 1 ). In addition, more than 40 molecules discovered by FBDD are currently in active clinical development ( Erlanson, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Using Structure-guided Fragment-Based Drug Discovery to Target Pseudomonas aeruginosa Infections in Cystic Fibrosis

Arif

Floto

Blundell

2022

Front. Mol. Biosci.

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Cystic fibrosis (CF) is progressive genetic disease that predisposes lungs and other organs to multiple long-lasting microbial infections. Pseudomonas aeruginosa is the most prevalent and deadly pathogen among these microbes. Lung function of CF patients worsens following chronic infections with P. aeruginosa and is associated with increased mortality and morbidity. Emergence of multidrug-resistant, extensively drug-resistant and pandrug-resistant strains of P. aeruginosa due to intrinsic and adaptive antibiotic resistance mechanisms has failed the current anti-pseudomonal antibiotics. Hence new antibacterials are urgently needed to treat P. aeruginosa infections. Structure-guided fragment-based drug discovery (FBDD) is a powerful approach in the field of drug development that has succeeded in delivering six FDA approved drugs over the past 20 years targeting a variety of biological molecules. However, FBDD has not been widely used in the development of anti-pseudomonal molecules. In this review, we first give a brief overview of our structure-guided FBDD pipeline and then give a detailed account of FBDD campaigns to combat P. aeruginosa infections by developing small molecules having either bactericidal or anti-virulence properties. We conclude with a brief overview of the FBDD efforts in our lab at the University of Cambridge towards targeting P. aeruginosa infections.

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Novel BCR-ABL1 tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia

Malik

Hassan

Eşkazan

2021

Expert Review of Hematology

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Asciminib in chronic myeloid leukemia: many questions still remain to be answered

Cited by 4 publications

References 11 publications

Health-related quality of life of patients with resistant/intolerant chronic phase chronic myeloid leukemia treated with asciminib or bosutinib in the phase 3 ASCEMBL trial

Health-related quality of life of patients with resistant/intolerant chronic phase chronic myeloid leukemia treated with asciminib or bosutinib in the phase 3 ASCEMBL trial

Using Structure-guided Fragment-Based Drug Discovery to Target Pseudomonas aeruginosa Infections in Cystic Fibrosis

Novel BCR-ABL1 tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia

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