Publications by authors named "Cony-Makhoul P"
The TOPASE study was set up to evaluate the outcomes of chronic myeloid leukaemia [CML] patients treated with ponatinib (PON) in a real-world setting in France. One hundred and twenty CML patients, 105 in chronic phase (CP), 8 in accelerated phase (AP) and 7 in blastic phase (BP) were included. Fifty-one (49%) of the CP-CML patients were in third line of treatment.
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- Autologous anti-CD19 CAR T cells are becoming standard treatment for relapsed/refractory large B-cell lymphoma, but serious side effects like cytokine release syndrome (CRS) and neurotoxicity (ICANS) pose risks, often requiring ICU care.
- In a study involving 925 patients in France, high rates of CRS (84.1%) and ICANS (40.5%) were observed, with significant proportions experiencing severe forms of these conditions.
- Two prognostic scoring systems (CRS-PSS and ICANS-PSS) were developed to identify patients at higher risk for severe CRS and ICANS based on specific clinical factors, and these scores were validated in other patient groups treated with similar therapies.
Article Synopsis
- In chronic myeloid leukemia, predicting stable treatment-free remission (TFR) after stopping tyrosine kinase inhibitors (TKIs) is difficult, especially using early molecular indicators.
- A study involving 408 patients compared various predictive tools, including the EUTOS long-term survival score, BCR::ABL1 transcript halving time, and residual disease measurements at months 3 and 6.
- While months 3 and 6 residual disease showed good predictive performance, particularly month 6, no early indicators effectively forecasted the TKI discontinuation criteria or TFR maintenance, indicating additional factors may be at play.
Article Synopsis
- Histologic transformation of Waldenström macroglobulinemia (HT-WM) usually results in a poor outlook when treated with standard therapies.* -
- This report presents the first cases of HT-WM being treated with chimeric antigen receptor T cells (CAR-T), which showed promising effectiveness.* -
- The treatment with CAR-T cells did not cause any unexpected side effects, indicating it might be a safer option for these patients.*
Article Synopsis
- Real-world data (RWD) are crucial for enhancing clinical trial (CT) findings, but challenges like data quality persist; the REALYSA study, launched in 2018, focuses on newly diagnosed lymphoma patients in France.
- A proof-of-concept analysis of 645 patients with diffuse large B-cell lymphoma (DLBCL) found high data completeness (<4% missing) and revealed good survival rates, with a median follow-up of 9.9 months showing 1-year event-free survival of 77.9% and overall survival of 90.0%.
- The study also assessed how well REALYSA's patient outcomes matched those from recent phase 3 trials (POLARIX and SENIOR), demonstrating
Article Synopsis
- Accelerated phase chronic myeloid leukemia (AP-CML) has a poorer prognosis than chronic phase (CP-CML), prompting researchers to test second-generation tyrosine kinase inhibitors (TKI2) as an initial treatment due to their reduced toxicity.
- In a study of 69 newly diagnosed patients with AP-CML, various health parameters were measured, revealing worse conditions in those with hematologic AP compared to cytogenetically defined AP.
- Regardless of the type of TKI2 treatment used, the patients achieved similar rates of clinical response and overall survival, suggesting that TKI2 can effectively manage AP-CML and mitigate the challenges associated with its advanced disease phase.
Efficacy and safety of nilotinib in chronic myeloid leukaemia patients who failed to achieve a treatment-free remission period after imatinib discontinuation: Results of the French Nilo post-STIM study.
Stéphanie Dulucq Françoise Rigal-Huguet Franck E Nicolini Pascale Cony-Makhoul Martine Escoffre-Barbe
Br J Haematol
June 2023
Article Synopsis
- Molecular recurrence (MRec) affects about 50% of chronic myeloid leukaemia (CML) patients who stop taking tyrosine kinase inhibitors (TKI) and occurs despite achieving sustained deep molecular responses.
- In a study involving 31 patients, 23 who switched to nilotinib (300 mg twice daily) maintained their molecular response for an average of 22 months, while seven experienced serious side effects leading to treatment discontinuation.
- The study found that 59.1% of patients remained treatment-free and maintained molecular response 24 months after stopping nilotinib, and 42.1% maintained it at 48 months, indicating promising results
Article Synopsis
- * It estimates a 10-year net survival rate of 65% and finds that the excess mortality hazard (EMH) associated with DLBCL decreases significantly after diagnosis, pointing to a lower long-term mortality risk for these patients.
- * Key factors influencing EMH include performance status, number of extra-nodal sites, and serum lactate dehydrogenase levels, with the study suggesting that the presence of extra-nodal sites might indicate other significant, yet unmeasured, prognostic variables.
Article Synopsis
- Familial forms of monoclonal gammopathy, including multiple myeloma (MM) and Monoclonal Gammopathy of Undetermined Significance (MGUS), are rare, with MGUS being more commonly observed and sometimes advancing to MM.
- A study identified 318 families with multiple cases of monoclonal gammopathy, highlighting potential genetic links and family clusters with parent-child and sibling cases.
- Despite some genetic similarities, familial cases generally present similarly to sporadic cases but show a better prognosis, with longer median survival rates for those with familial MM.
Article Synopsis
- - RNA splicing factors can play roles as both cancer-promoting proteins (oncoproteins) and tumor suppressors, and their alteration in cancer drives interest in targeting splicing mechanisms for treatment.
- - In a study on chronic myeloid leukemia (CML), researchers found that specific DNA methylation changes affected splicing in CML cells, indicating potential alterations in splicing proteins at diagnosis.
- - The investigation revealed a distinct splicing profile in CML cells compared to healthy cells and showed that combining traditional treatments with a spliceosome-targeted drug enhanced efficacy against CML without harming healthy cells, suggesting new treatment avenues.
Article Synopsis
- * A total of 79 patients participated, and the primary goal was to assess the cumulative molecular response rates over 12 months, with results showing significant rates of deep molecular response at 5 years.
- * While grade 3 neutropenia was common, it didn't lead to severe infections, and most patients continued the Peg-IFN treatment for a substantial time, resulting in notable molecular response rates after 12 and 24 months.
Article Synopsis
- - The EUROPE phase 2 trial examined how well biomarkers predict the effectiveness of romiplostim (ROM) treatment for patients with lower-risk myelodysplastic neoplasms (LR-MDS) and low platelet counts, involving 77 patients from the EMSCO network.
- - Out of the participants, 42% showed significant improvements in platelet counts, lasting a median of 340 days, while other types of responses (neutrophil and erythroid) were much less common.
- - The study found that while certain mutations (like SRSF2) and baseline hemoglobin levels were linked to positive responses, ROM treatment did not affect the progression of genetic mutations in patients, confirming its safety and efficacy.
Article Synopsis
- * A total of 133 patients were assessed, and of the 86 who were identified as underdosed, those in the TDM group had higher imatinib levels and a significantly better major molecular response (MMR) at 12 months (67% for TDM vs. 39% for control).
- * TDM proved to be a feasible approach that not only heightened drug levels but also maintained a positive impact on treatment outcomes for up to three years.
Article Synopsis
- Myeloproliferative neoplasms (MPNs) are rare in individuals under 25, and a study examined 444 such patients over a median follow-up of 9.7 years across 38 centers globally.
- The study found that 11.1% had a history of thrombosis, with higher risks associated with the JAK2V617F mutation and hyperviscosity symptoms, while new thrombotic and hemorrhagic events occurred at significant rates.
- It highlighted that disease transformation, particularly to myelofibrosis, was common, with splenomegaly identified as a new risk factor, indicating a need for updated management guidelines for young MPN patients.
Article Synopsis
- Discontinuing tyrosine kinase inhibitors in chronic phase chronic myeloid leukemia (CML) is feasible, but more research is needed on factors that predict recurrence after stopping treatment and the long-term effects of treatment-free remission (TFR).
- In a study updating data from the STIM2 trial, 199 patients were analyzed, showing a significant percentage (43.4%) achieved TFR at 5 years, but many experienced a loss of major molecular response over time.
- The timing of molecular recurrence varied, with most recurrences occurring within the first 6 months after stopping treatment, and certain factors such as treatment duration and molecular response levels were linked to recurrence within the first 24 months but not later.
Article Synopsis
- MDS-RS patients experience chronic anemia and often become dependent on red blood cell transfusions, with a low risk of developing acute myeloid leukemia.
- In a 6-month study involving 100 transfusion-dependent patients across 12 French centers, researchers examined transfusion patterns, hospitalization frequency, care costs, and related health issues.
- Results showed that 79% of patients had a high transfusion burden, leading to increased hospital visits and significant treatment costs (16,188€ per patient), highlighting the need to evaluate more effective treatment options.
Article Synopsis
- * The research included 507 patients diagnosed between 2006 and 2016, revealing that 22% participated in clinical trials, and overall survival pathways varied while some patients transitioned to second-line treatments or stopped therapy.
- * Despite showing improvements in initial responses for NG-TKI, the study did not definitively conclude that NG-TKI is superior to IM in terms of survival and tolerance, indicating that further research is necessary. *
Article Synopsis
- Dasatinib, a medication for chronic myeloid leukaemia (CML), was studied for its potential to cause pleural effusion (fluid buildup in the lungs) in patients taking it.
- A clinical trial was conducted with patients taking 100 mg of dasatinib, assessing whether therapeutic drug monitoring (TDM) could reduce significant side effects by comparing a dose-reduction strategy with standard care.
- Although the main goal of reducing adverse events wasn't achieved due to early complications, TDM significantly lowered the incidence of pleural effusion in the long run while maintaining similar molecular responses across treatment groups.
Article Synopsis
- The study explores the genetic factors associated with the 14q32 duplication that affects the ATG2B/GSKIP genes, linked to various myeloid neoplasms in families.
- Among 12 asymptomatic carriers and 52 affected patients, 75% of healthy carriers showed early signs of clonal hematopoiesis primarily due to TET2 mutations.
- Two clonal expansion routes were identified: one leading to myeloproliferative neoplasms (MPN) driven by TET2 and RAS mutations, and the other to acute myeloid leukemia (AML) without prior MPN, with no DNMT3A mutations found in the cohort.
Article Synopsis
- Thrombocytopenia in MDS and CMML:
- Despite being moderate in prevalence for low-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML), thrombocytopenia poses significant risks for severe bleeding, and current treatment options remain limited.
- Efficacy of Eltrombopag (ELT):
- In a retrospective study involving 61 patients (50 with MDS and 11 with CMML), ELT demonstrated a platelet response in 77% of patients, with a median duration of response lasting about 8 months, and none of the patients who stopped treatment relapsed within a follow-up period.
- Safety and Comp
Article Synopsis
- Accumulation of nilotinib in target cells is crucial for effective targeted therapy in Chronic Phase-Chronic Myeloid Leukaemia (CP-CML), where response to treatment varies widely among patients.
- A study using flow cytometry revealed that a significant portion of CP-CML cells, including 13.3% of mature polymorphonuclear cells and 40% of immature CD34 cells, did not retain detectable levels of nilotinib, impacting its efficacy.
- The research indicated that the level of nilotinib in cells correlates with disease burden and early treatment response, highlighting the importance of understanding individual and intra-clonal differences in drug accumulation for better patient outcomes.
Article Synopsis
- The study looked at how different gene mutations affect the health of people with myelofibrosis, a type of blood disease.
- Researchers analyzed 479 patients and grouped them based on specific mutations to see how these groups relate to worsening conditions or death.
- They found that mutations in certain genes like TP53 and high-risk genes made it more likely for patients to get worse or die, while a mutation in the ASXL1 gene alone didn’t have a significant negative impact.
Purpose: Tyrosine kinase inhibitors (TKIs) have dramatically improved the prognosis of chronic myeloid leukemia (CML). We aimed to assess health state utility and quality of life (QoL) in French patients with CML in real-life setting, to study the determinants of utility score and to compare health-related QoL values to general population norms.
Methods: We conducted a cross-sectional study in 412 patients with CML.
Article Synopsis
- - The SPIRIT trial is a long-term study that compares the effectiveness of various treatments for chronic-phase chronic myeloid leukaemia (CML), involving 787 patients followed for an average of 13.5 years.
- - Overall and progression-free survival rates after 15 years were similar across four treatment groups, ranging from 80% to 87%, suggesting comparable effectiveness of different combinations.
- - The combination of imatinib with pegylated interferon alpha2a resulted in significantly better molecular response rates compared to imatinib alone, although toxicity led to treatment cessation for some patients.