Publications by authors named "Robrecht S"
Purpose: The CLL12 trial reassesses the watch-and-wait consensus for early-stage chronic lymphocytic leukemia (CLL) in the context of targeted therapies.
Methods: The German CLL Study Group conducted a randomized, double-blind, placebo-controlled phase III trial with 363 patients with asymptomatic, treatment-naïve Binet stage A CLL at increased risk of progression to receive ibrutinib (n = 182) at a daily dose of 420 mg or placebo (n = 181). Additionally, 152 low-risk patients were allocated to the watch-and-wait group.
Purpose: Surrogate end points are commonly used to estimate treatment efficacy in clinical studies of chronic lymphocytic leukemia (CLL). This patient- and trial-level analysis describes the correlation between progression-free survival (PFS) and minimal residual disease (MRD) with overall survival (OS) in first-line trials for CLL.
Patients And Methods: First, patient-level correlation was confirmed using source data from 12 frontline German CLL Study Group (GCLLSG)-trials.
In the CLL14 study, patients with previously untreated chronic lymphocytic leukemia (CLL) and coexisting conditions were randomized to 12 cycles of venetoclax-obinutuzumab (Ven-Obi, n = 216) or chlorambucil-obinutuzumab (Clb-Obi, n = 216). Progression-free survival (PFS) was the primary end point. Key secondary end points included time-to-next-treatment (TTNT), rates of undetectable minimal residual disease (uMRD), overall survival (OS), and rates of adverse events.
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- The GAIA/CLL13 trial found that venetoclax-obinutuzumab and venetoclax-obinutuzumab-ibrutinib combinations led to better undetectable measurable residual disease (MRD) rates and longer progression-free survival compared to traditional chemoimmunotherapy for untreated chronic lymphocytic leukaemia (CLL) patients.
- The trial was a phase 3 study involving 159 sites across Europe and the Middle East, enrolling patients aged 18 and older with specific health criteria and assigning them to different treatment groups, including standard chemoimmunotherapy and various venetoclax-based combinations.
- All treatment regimens were administered in cycles, with detailed protocols for each group, specifically focusing on
Long-term data of chronic lymphocytic leukemia (CLL) patients with favorable risk who were treated with fludarabine, cyclophosphamide, and rituximab (FCR) within clinical trials show good efficacy. We here report long-term data collected within the GCLLSG registry. Altogether, 417 CLL patients who received first-line treatment with FCR were analyzed, of which 293 (70.
View Article and Find Full Text PDFWe evaluated the chronic lymphocytic leukemia International Prognostic Index (CLL-IPI) in patients with CLL treated first line with targeted drugs (n = 991) or chemoimmunotherapy (n = 1256). With a median observation time of 40.5 months, the 3-year progression-free survival (PFS) rates for targeted drug-treated patients varied by CLL-IPI risk group: 96.
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- The phase 2 CLL2-BAAG trial evaluated a combination therapy of acalabrutinib, venetoclax, and obinutuzumab in 45 patients with relapsed/refractory chronic lymphocytic leukemia (CLL), focusing on measurable residual disease (MRD) outcomes.
- 93.3% of patients achieved undetectable MRD (<10-4) at any time point, showing the treatment's effectiveness, including those previously exposed to other therapies.
- The study indicated high 3-year progression-free and overall survival rates (85.0% and 93.8%, respectively) and highlighted that integrating circulating tumor DNA (ctDNA) analysis with traditional methods improved early relapse detection
Objective: Preventing severe COVID-19 remains a priority globally, particularly in the immunocompromised population. As shown in healthy individuals, immunity against SARS-CoV-2 can be yielded by previous infection, vaccination, or both (hybrid immunity). The objective of this observation study was to investigate hybrid immunity in patients with chronic lymphocytic leukemia (CLL).
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- This study focuses on patients with Richter transformation (RT) in chronic lymphocytic leukemia, showcasing a phase 2 trial where patients were treated with a combination of two drugs, tislelizumab and zanubrutinib, for 12 cycles.* -
- Of 48 patients analyzed, 58.3% showed a positive response to the treatment, with some achieving complete or partial remission, thus surpassing the study's response rate goal.* -
- The results indicate that this combination therapy not only has a solid response rate but also leads to a 12-month survival rate of 74.7%, though common side effects included infections and gastrointestinal issues.*
Article Synopsis
- * After 6 cycles of treatment, a complete remission rate of 58.5% was achieved, with impressive 36-month progression-free and overall survival rates of 79.9% and 92.6%, respectively.
- * Although some adverse effects like neutropenia and infections were noted, the regimen demonstrated a manageable safety profile, making it a promising option for first-line treatment in high-risk CLL patients.
Idelalisib in combination with rituximab is an efficacious treatment for patients suffering from chronic lymphocytic leukemia (CLL) with known limitations due to toxicities. However, the benefit after prior Bruton tyrosine kinase inhibitor (BTKi) therapy remains unclear. For this analysis, 81 patients included in a non-interventional registry study of the German CLL study group (registered at www.
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- Complex karyotypes (CKTs) and highly complex karyotypes (hCKTs) are significant predictors of worse outcomes in chronic lymphocytic leukemia (CLL) when treated with chemoimmunotherapy, and their impact is further explored in venetoclax-based therapies.
- * In a study involving 895 patients, CKTs were linked to shorter progression-free survival (PFS) and overall survival (OS) in the CIT group, while hCKTs negatively affected PFS in the venetoclax group.
- * The findings suggest that karyotype analysis should be included in standard CLL diagnostics to better identify patients at high risk for poor treatment outcomes, supporting more personalized treatment approaches.
Article Synopsis
- The study investigates the effectiveness of venetoclax combined with anti-CD20 antibodies in fit patients with advanced chronic lymphocytic leukemia (CLL), compared to traditional chemoimmunotherapy.
- In a phase 3 trial with 926 participants, various treatment regimens were compared, emphasizing the primary goals of achieving undetectable minimal residual disease and prolonging progression-free survival.
- Results showed that venetoclax combinations significantly outperformed chemoimmunotherapy in terms of undetectable minimal residual disease rates and 3-year progression-free survival, especially in the venetoclax-obinutuzumab-ibrutinib group.
Data on long-term outcomes and biological drivers associated with depth of remission after BCL2 inhibition by venetoclax in the treatment of chronic lymphocytic leukemia (CLL) are limited. In this open-label parallel-group phase-3 study, 432 patients with previously untreated CLL were randomized (1:1) to receive either 1-year venetoclax-obinutuzumab (Ven-Obi, 216 patients) or chlorambucil-Obi (Clb-Obi, 216 patients) therapy (NCT02242942). The primary endpoint was investigator-assessed progression-free survival (PFS); secondary endpoints included minimal residual disease (MRD) and overall survival.
View Article and Find Full Text PDFIn chronic lymphocytic leukemia (CLL), epigenetic alterations are considered to centrally shape the transcriptional signatures that drive disease evolution and underlie its biological and clinical subsets. Characterizations of epigenetic regulators, particularly histone-modifying enzymes, are very rudimentary in CLL. In efforts to establish effectors of the CLL-associated oncogene T-cell leukemia 1A (TCL1A), we identified here the lysine-specific histone demethylase KDM1A to interact with the TCL1A protein in B cells in conjunction with an increased catalytic activity of KDM1A.
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- Upregulation of the TCL1A proto-oncogene is linked to various aggressive B-cell and T-cell cancers, but its mechanisms, especially in the nucleus, are not fully understood.
- Research showed that TCL1A influences lymphomagenesis in mouse models by altering nuclear organization and interacts with proteins that regulate the cell cycle and DNA repair, notably CDC20.
- High levels of TCL1A correlate with faster cell cycle transitions, increased chromosome missegregation, and aneuploidy, suggesting TCL1A disrupts normal cell cycle control, potentially leading to more aggressive forms of cancer.
Article Synopsis
- - Patients aged 80 and older represent a significant portion of chronic lymphocytic leukemia (CLL) cases but are often excluded from clinical trials, making it hard to assess treatment efficacy in this age group.
- - An analysis of six trials involving targeted treatments such as venetoclax and ibrutinib showed a promising 73% overall response rate among the 33 older patients studied, despite many having serious health issues.
- - The median progression-free survival for these patients was impressive at 49.2 months, indicating that targeted therapies are both feasible and effective, suggesting the need for more tailored studies for older CLL patients.
The sensitivity of conventional techniques for reliable quantification of minimal/measurable residual disease (MRD) in chronic lymphocytic leukemia (CLL) is limited to MRD 10-4. Measuring MRD <10-4 could help to further distinguish between patients with CLL with durable remission and those at risk of early relapse. We herein present an academically developed immunoglobulin heavy-chain variable (IGHV) leader-based next-generation sequencing (NGS) assay for the quantification of MRD in CLL.
View Article and Find Full Text PDFBackground: Although BTK inhibitors provide long-term disease-control in patients with chronic lymphocytic leukaemia, they need to be combined with BCL2 inhibitors or antibodies to achieve deep responses with undetectable minimal residual disease (uMRD), which allows for time-limited treatment. This trial aims to evaluate the triple combination of obinutuzumab, acalabrutinib, and venetoclax after an optional debulking with bendamustine.
Methods: This multicentre, open-label, investigator-initiated, phase 2 study evaluates a sequential treatment consisting of a debulking with two cycles of bendamustine for patients with a higher tumour load (70 mg/m intravenously on days 1 and 2, repeated after 28 days), followed by an induction and a maintenance with obinutuzumab (1000 mg intravenously on days 1-2, 8, and 15 of the first induction cycle, every 4 weeks in induction cycles 2-6 and every 12 weeks in the maintenance phase), acalabrutinib (100 mg orally twice daily continuously from induction cycle 2 day 1 onwards) and venetoclax (starting in induction cycle 3 with 20 mg per day with a weekly dose ramp-up over 5 weeks to the target dose of 400 mg per day).