Publications by authors named "Martine Escoffre-Barbe"
Purpose: The use of inotuzumab ozogamicin (InO), a conjugated anti-CD22 monoclonal antibody, is becoming a promising frontline treatment for older patients with ALL.
Patients And Methods: EWALL-INO is an open-label prospective multicenter phase II trial (ClinicalTrials.gov identifier: NCT03249870).
Background: CASSIOPEIA part 1 demonstrated superior depth of response and prolonged progression-free survival with daratumumab in combination with bortezomib, thalidomide, and dexamethasone (D-VTd) versus bortezomib, thalidomide, and dexamethasone (VTd) alone as an induction and consolidation regimen in transplant-eligible patients newly diagnosed with myeloma. In CASSIOPEIA part 2, daratumumab maintenance significantly improved progression-free survival and increased minimal residual disease (MRD)-negativity rates versus observation. Here, we report long-term study outcomes of CASSIOPEIA.
View Article and Find Full Text PDFThe initial molecular response predicts the deep molecular response but not treatment-free remission maintenance in a real-world chronic myeloid leukemia cohort.
Haematologica
September 2024
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.
We previously demonstrated that a reduced-intensity chemotherapy schedule can safely replace hyper-CVAD (cyclophosphamide-vincristine-doxorubicin [Adriamycin]-dexamethasone) cycle 1 when combined with imatinib in adults with Philadelphia-positive acute lymphoblastic leukemia. In the present randomized GRAAPH-2014 trial, we used nilotinib and addressed the omission of cytarabine (Ara-C) in consolidation. The primary objective was the major molecular response (MMR) rate measured by BCR::ABL1 quantification after cycle 4 (end of consolidation).
View Article and Find Full Text PDFLow non-relapse mortality and good haematological and renal responses after autologous haematopoietic stem cell transplantation in multiple myeloma patients with renal insufficiency at transplant: A prospective Société Francophone de Greffe de Moelle-Thérapie Cellulaire observational study.
Br J Haematol
April 2024
Article Synopsis
- * In a study of 50 patients with severe renal impairment, only one death occurred within the first 100 days post-transplant, with most patients showing significant improvements in hematological responses.
- * Overall, after two years, 84% of patients were alive, 70% were free from disease progression, and 59% saw an improvement in kidney function, indicating that the procedure is both safe and effective for this population.
Article Synopsis
- * In a study of 1091 adult patients, 12.9% had KMT2A-r, with a 5-year relapse rate of 40.7% and overall survival rate of 53.3%. The presence of specific gene alterations like TP53 and IKZF1 correlated with significantly worse outcomes.
- * The analysis showed that measuring minimal residual disease (MRD) using KMT2A markers was more reliable than other methods, indicating that patients responding well early
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.
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
Lenalidomide maintenance in myeloma is well established. Nevertheless, pomalidomide could provide an alternative. Myeloma patients in first relapse, initially treated in the Intergroupe Francophone du Myélome (IFM) 2009 trial, and subsequently in the IFM 2013-01 phase 2 trial, received four cycles of salvage therapy with pomalidomide plus cyclophosphamide plus dexamethasone (PCD) with transplantation plus 2 PCD consolidation or without transplantation but with 5 PCD and for all patients pomalidomide plus dexamethasone maintenance therapy.
View Article and Find Full Text PDFArticle 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
- * 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
- 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
- High-dose melphalan (HDM) combined with bortezomib (Bor-HDM) was tested in a phase 3 trial for patients with multiple myeloma to see if it was more effective than HDM alone.* -
- The trial included 300 patients, and results showed no significant differences in complete response rates or minimum residual disease rates between the two treatment groups.* -
- Although progression-free survival was slightly better in the Bor-HDM group (34.0 months) compared to HDM (29.6 months), the overall survival rates and serious adverse events were similar, indicating Bor-HDM did not provide a clear advantage.*
High tumor burden before blinatumomab has a negative impact on the outcome of adult patients with B-cell precursor acute lymphoblastic leukemia. A real-world study by the GRAALL.
Haematologica
September 2022
Article Synopsis
- Blinatumomab is a bispecific T-cell engager used for treating B-cell precursor acute lymphoblastic leukemia (B-ALL) in patients who have minimal residual disease (MRD) or are in relapse, with a study analyzing 73 patients receiving this treatment.
- The results showed that high pre-treatment MRD levels correlated with poorer outcomes, specifically shorter relapse-free survival and overall survival rates.
- The study suggests that understanding tumor burden prior to treatment could lead to more personalized strategies for managing relapsed patients, highlighting the importance of MRD levels in treatment planning.
We report a case of severe refractory hepato-splenic candidiasis confirmed following splenectomy in an immunocompromised 54-year-old woman treated for acute lymphoblastic leukemia. Liver biopsies did not contribute to identifying the etiology of the multiple hepato-splenic lesions. In view of the lack of improvement after several lines of antifungal treatments, a splenectomy was performed and confirmed splenic candidiasis.
View Article and Find Full Text PDFBackground: CASSIOPEIA part 1 showed superior depth of response and significantly improved progression-free survival with daratumumab, bortezomib, thalidomide, and dexamethasone (D-VTd) versus bortezomib, thalidomide, and dexamethasone (VTd) as induction and consolidation in patients with autologous stem-cell transplant (ASCT)-eligible newly diagnosed multiple myeloma. In part 2, we compared daratumumab maintenance versus observation only.
Methods: CASSIOPEIA is a two-part, open-label, randomised, phase 3 trial of patients aged 18-65 years with newly diagnosed multiple myeloma and Eastern Cooperative Oncology Group performance status 0-2, done in 111 European academic and community practice centres.
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.
Bortezomib, lenalidomide, and dexamethasone plus transplant is a standard of care for eligible patients with multiple myeloma. Because responses can deepen with time, regimens with longer and more potent induction/consolidation phases are needed. In this phase 2 study, patients received eight 28-day cycles of carfilzomib (K) 20/36 mg/m2 (days 1-2, 8-9, 15-16), lenalidomide (R) 25 mg (days 1-21), and dexamethasone (d) 20 mg (days 1-2, 8-9, 15-16, 22-23).
View Article and Find Full Text PDFArticle 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.
Article Synopsis
- In the context of chronic myeloid leukemia (CML) that doesn't respond to tyrosine kinase inhibitors (TKIs), BCR-ABL1 tyrosine kinase domain (TKD) mutations are crucial for guiding treatment decisions.
- A panel of experts emphasizes the importance of mutation testing, recommending it primarily in cases of treatment failure, while suggesting discussions for patients facing moderate warning signs based on specific factors.
- Next-generation sequencing (NGS) is recommended for its superior sensitivity in detecting mutations, with therapeutic choices based on the specific mutations identified and their resistance implications, while the utility of even more sensitive testing methods remains to be understood.
Evaluation of Residual Disease and TKI Duration Are Critical Predictive Factors for Molecular Recurrence after Stopping Imatinib First-line in Chronic Phase CML Patients.
Clin Cancer Res
November 2019
Purpose: Tyrosine kinase inhibitor (TKI) discontinuation is an emerging goal in chronic myelogenous leukemia (CML) management and several studies have demonstrated the feasibility of safely stopping imatinib. A sustained deep molecular response on long-term TKI is critical prior to attempting treatment-free remission. Reproducible results from several studies reported recently, failed to identify robust and reproducible predictive factors for the selection of the best candidates for successful TKI cessation.
View Article and Find Full Text PDFThe effectiveness of tyrosine kinase inhibitors (TKIs) has made it possible to consider treatment discontinuation in chronic myeloid leukaemia (CML) patients that achieve an excellent response. However, a few of the patients included in the Europe Stop Tyrosine Kinase Inhibitors (EURO-SKI) trial reported musculoskeletal pain shortly after stopping TKIs, considered as a withdrawal syndrome (WS). To identify factors that may predispose to TKI WS, we analysed the pharmacovigilance declarations for the 6 months after stopping TKIs in a large cohort of CML (n = 427) that combined the French patients included in the STop IMatinib 2 (STIM2; n = 224) and EURO-SKI (n = 203) trials.
View Article and Find Full Text PDFBackground: Bortezomib, thalidomide, and dexamethasone (VTd) plus autologous stem-cell transplantation is standard treatment in Europe for transplant-eligible patients with newly diagnosed multiple myeloma. We evaluated whether the addition of daratumumab to VTd before and after autologous stem-cell transplantation would improve stringent complete response rate in patients with newly diagnosed multiple myeloma.
Methods: In this two-part, randomised, open-label, phase 3 CASSIOPEIA trial, we recruited transplant-eligible patients with newly diagnosed multiple myeloma at 111 European sites.
It is important to have an effective therapy for patients with multiple myeloma (MM) at first relapse, particularly if an autologous stem cell transplant (ASCT) is considered at this stage. This multicenter, phase 2 trial evaluated the efficacy and safety of weekly oral pomalidomide-cyclophosphamide-dexamethasone (PCD) in patients with MM in first relapse after treatment with lenalidomide-bortezomib-dexamethasone (RVD). All patients had received RVD as induction and consolidation therapy, plus lenalidomide maintenance for 1 year (arm A).
View Article and Find Full Text PDFArticle Synopsis
- Ponatinib shows promise for treating chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) patients who didn't respond to other therapies, but it has notable toxicity risks.
- A national observational study tracked 48 CML patients with a median follow-up of over 26 months, revealing overall survival rates and major molecular response rates comparable to earlier clinical trials.
- The study also highlighted an increased rate of cardiovascular issues among patients taking ponatinib, leading to recommendations for better management of cardiovascular risks and careful patient selection.