Publications by authors named "Lionel Ades"
Unlabelled: This phase 2 study investigated pevonedistat + azacitidine + venetoclax ( = 83) versus azacitidine + venetoclax ( = 81) in patients with newly diagnosed acute myeloid leukemia (AML) ineligible for intensive chemotherapy. The study was stopped early following negative results from PANTHER, which evaluated pevonedistat in higher-risk myelodysplastic syndromes/chronic myelomonocytic leukemia or low-blast AML. Outcomes were analyzed up to the datacut.
View Article and Find Full Text PDFProspective feasibility of a minimal BH3 profiling assay in acute myeloid leukemia.
Cytometry B Clin Cytom
November 2024
BH3 profiling can assess global mitochondrial priming and dependence of leukemic cells on specific BH3 anti-apoptotic proteins such as BCL-2. In acute myeloid leukemia (AML), proof-of-concept prognostic studies have been performed on archived samples variably accounting for molecular genetics. We undertook a single-center feasibility study of a simplified flow-based assay to determine the absolute mitochondrial priming and BCL-2 dependence in consecutive AML patients.
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CPX-351 has been approved for patients with therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (MRC-AML). No extensive data are available on MRD and long-term clinical outcome using CPX-351 in AML in real-life. We retrospectively collected data from 168 patients in 36 centers in France and Italy who had received one or two cycles of induction with CPX-351.
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- The WHO and International Consensus Classification 2022 aim to improve diagnosis and treatment decisions for myelodysplastic syndromes, but disparities in their implementation exist.
- A panel of experts used a data-driven method and the Delphi consensus process to align the two classifications, focusing on genomic features to create harmonized labels for distinct clusters.
- Key findings identified nine genomic clusters, with the most significant linked to biallelic TP53 inactivation, and highlighted the inadequacy of traditional morphological assessments in capturing the complexity of these diseases.
Article Synopsis
- * The study, called KOMET-001, was conducted in multiple countries and involved dose-escalation and validation phases, with patients in specific molecular subtypes receiving varying doses of ziftomenib over 28-day cycles.
- * Results indicated that 83 patients were treated with ziftomenib from September 2019 to August 2022, and the findings are crucial for determining the drug's safety and effectiveness for future phases of clinical testing.
Introduction: The objective of this study was to describe kidney involvement in patients with myelodysplastic syndromes (MDS), their treatments, and outcomes.
Methods: We conducted a multicenter retrospective study in seven centers, identifying MDS patients with acute kidney injury (AKI), chronic kidney disease (CKD), and urine abnormalities.
Results: Fifteen patients developed a kidney disease 3 months after MDS diagnosis.
Article Synopsis
- Myelodysplastic syndromes (MDS) are blood disorders marked by irregularities in myeloid cells and low blood cell counts, often caused by genetic mutations, though classification has mostly focused on cell appearance.
- A study analyzing genomic data from over 3,200 MDS patients identified 16 distinct molecular subtypes, revealing varied clinical outcomes, with the majority of patients (86%) fitting into specific genetic groups linked to different survival rates.
- The findings suggest that understanding these genetically defined subgroups can enhance MDS classification and inform future treatment strategies, emphasizing the importance of genetic insight in managing the disease.
Dose-limiting toxicity poses a major limitation to the clinical utility of targeted cancer therapies, often arising from target engagement in nonmalignant tissues. This obstacle can be minimized by targeting cancer dependencies driven by proteins with tissue-restricted and/or tumor-restricted expression. In line with another recent report, we show here that, in acute myeloid leukemia (AML), suppression of the myeloid-restricted PIK3CG/p110γ-PIK3R5/p101 axis inhibits protein kinase B/Akt signaling and compromises AML cell fitness.
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- Advancements in understanding myelodysplastic neoplasms (MDS) have revealed important cellular and molecular factors that influence disease progression, highlighting the significance of immune dysregulation in the bone marrow during MDS evolution.
- Despite these advancements, immunotherapy for MDS has lagged due to a lack of effective immune classifications for patient stratification and no widely accepted immune panels for clinical use.
- To address these challenges, the i4MDS consortium proposes standardized immune monitoring approaches, including flow cytometry panels and cytokine assays, aiming to improve patient stratification and develop predictive markers for treatment response in MDS.
Article Synopsis
- Allogeneic hematopoietic stem-cell transplantation is the only curative option for patients with myelodysplastic syndromes, and the timing of this treatment is crucial for maximizing benefits and minimizing risks.
- A decision support system was developed to identify the optimal timing for HSCT based on clinical and genomic data from a large study of over 7,000 patients, comparing outcomes using the Molecular International Prognostic Scoring System (IPSS-M) against traditional scoring methods.
- The findings suggest that patients with lower risk can benefit from delaying transplantation, while those at higher risk should undergo it immediately, indicating that the IPSS-M strategy significantly improves life expectancy and supports personalized treatment plans.
Article Synopsis
- Mutations in the UBA1 gene, which are linked to VEXAS syndrome, have been found in patients with myelodysplastic syndromes (MDS), with a study identifying 7% of a cohort having specific UBA1 mutations.
- An additional sequencing analysis of a larger group revealed 1% with other potentially harmful variants, and all 40 identified patients with likely/pathogenic mutations were male with various MDS subtypes.
- Most patients with UBA1 mutations exhibited symptoms consistent with VEXAS syndrome, suggesting that routine screening for UBA1 mutations should be considered in MDS management.
Myelodysplastic syndromes (MDS) with mutated SF3B1 gene present features including a favourable outcome distinct from MDS with mutations in other splicing factor genes SRSF2 or U2AF1. Molecular bases of these divergences are poorly understood. Here we find that SF3B1-mutated MDS show reduced R-loop formation predominating in gene bodies associated with intron retention reduction, not found in U2AF1- or SRSF2-mutated MDS.
View Article and Find Full Text PDFNon-intensive therapies such as the hypomethylating agent (HMA) azacitidine (AZA) have been used in patients with AML ineligible for intensive induction chemotherapy (IC) or stem cell transplant due to advanced age, comorbidities, and/or risk factors. However, response rates and survival remain dismal. Pre-clinical studies indicate the epigenetic combination of HMAs and HDAC inhibitors induce re-expression of silenced genes synergistically.
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- - Recent advancements in the treatment of high-risk Myelodysplastic Neoplasms (HR MDS) face obstacles due to changing drug combinations with Hypomethylating Agents (HMAs) and a shift from the IPSS to IPSS-M scoring system.
- - The introduction of MDS/AML overlap and the inclusion of chronic myelomonocytic leukemia (CMML) add further complexity to study classifications and trial designs.
- - Emphasizing the need for precise trial methodologies, the text discusses the importance of accurately reporting adverse events and reviewing negative clinical trials to improve future research in HR MDS.