Results of the randomized phase IIB ARCTIC trial of low-dose rituximab in previously untreated CLL

Howard, Dena; Munir, Talha; McParland, Lucy; Rawstron, Andrew; Milligan, Donald; Schuh, Anna; Hockaday, Anna; Allsup, David; Marshall, Scott; Duncombe, Andrew; O’Dwyer, John; Smith, Andrew; Longo, Roberta; Varghese, Abraham; Hillmen, Peter

doi:10.1038/leu.2017.96

Cited by 25 publications

(34 citation statements)

References 24 publications

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“…Tumour (peripheral blood) and germline (GL; saliva) samples from 64 patients with CLL recruited into the ADMIRE (Munir et al , ; n = 33) and ARCTIC (Howard et al , ; n = 31) studies and who were consented for WGS, were randomly selected (total n = 250; REC 09/H1306/54). Baseline patient characteristics are provided in Table SI.…”

Section: Methodsmentioning

confidence: 99%

Clinical‐grade validation of whole genome sequencing reveals robust detection of low‐frequency variants and copy number alterations in CLL

et al. 2018

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The 100 000 Genome Project aims to develop a diagnostics platform by introducing whole genome sequencing (WGS) into clinical practice. Samples from patients with chronic lymphocytic leukaemia were subjected to WGS. WGS detection of single nucleotide variants and insertion/deletions were validated by targeted next generation sequencing showing high concordance (96·3%), also for detection of sub-clonal variants and low-frequency TP53 variants. Copy number alteration detection was verified by fluorescent in situ hybridisation and genome-wide single nucleotide polymorphism array (concordances of 86·7% and 92·9%, respectively), confirming adequate sensitivity by WGS. Our results confirm that WGS can provide comprehensive genomic characterisation for clinical trials, drug discovery and, ultimately, precision medicine.

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Section: Methodsmentioning

confidence: 99%

Clinical‐grade validation of whole genome sequencing reveals robust detection of low‐frequency variants and copy number alterations in CLL

et al. 2018

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“…Recently, Wojdacz et al, applied these epigenetic classifications in the setting of CIT in a retrospective study of 605 treatment-naïve patients enrolled in three chemotherapy and CIT trials from the United Kingdom: (1) CLL4 which compared chlorambucil and fludarabine with or without cyclophosphamide [96], (2) ADMIRE which compared the efficacy of FCR against FCR and mitoxantrone [97], and (3) ARCTIC which compared FCR with FC mitoxantrone, and low-dose rituximab [98]. Multivariate Cox proportional analysis identified m-CLL as an independent prognostic factor for OS (HR, 0.46; 95% CI, 0.24-0.87; p = 0.018) in CLL4, and PFS (HR, 0.25; 95% CI, 0.10-0.57; p = 0.002) in ARCTIC and ADMIRE patients [99].…”

Section: Dna Methylationmentioning

confidence: 99%

An Updated Perspective on Current Prognostic and Predictive Biomarkers in Chronic Lymphocytic Leukemia in the Context of Chemoimmunotherapy and Novel Targeted Therapy

Cohen

Bomben

Pozzo

et al. 2020

Cancers

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Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with a variable clinical course. Novel biomarkers discovered over the past 20 years have revolutionized the way clinicians approach prognostication and treatment especially in the chemotherapy-free era. Herein, we review the best established prognostic and predictive biomarkers in the setting of chemoimmunotherapy (CIT) and novel targeted therapy. We propose that TP53 disruption (defined as either TP53 mutation or chromosome 17p deletion), unmutated immunoglobulin heavy chain variable region gene status (UM IGHV), NOTCH1 mutation, and CD49d expression are the strongest prognosticators of disease progression and overall survival in the field of novel biomarkers including recurrent gene mutations. We also highlight the predictive role of TP53 disruption, UM IGHV, and NOTCH1 mutation in the setting of CIT and TP53 disruption and CD49d expression in the setting of novel targeted therapy employing B-cell receptor (BCR) and B-cell lymphoma-2 (BCL2) inhibition. Finally, we discuss future directions in the field of biomarker development to identify those with relapsed/refractory disease at risk for progression despite treatment with novel therapies.

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“…The pivotal German CLL8 study showed that the addition of rituximab (R) to the chemotherapy backbone (fludarabine and cyclophosphamide, FC) improved not just progression‐free survival (PFS) but also overall survival (OS) of fit patients with CLL (Hallek et al , ). Subsequently, both the UK's ARCTIC and ADMIRE trials (Howard et al , ; Munir et al , ) and the German CLL10 trial (Eichhorst et al , ) provided further evidence that FCR remains the treatment of choice for fit patients.…”

Section: Front‐line Therapymentioning

confidence: 99%

“…In addition, the ARCTIC, ADMIRE and Cancer Trials Ireland studies demonstrated that rituximab with oral administration of FC yields high rates of response and rates of minimal residual disease (MRD) negativity compared to historical series using intravenous FC (Appleby et al , ; Howard et al , ; Munir et al , ).…”

Section: Front‐line Therapymentioning

confidence: 99%

Guideline for the treatment of chronic lymphocytic leukaemia

et al. 2018

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Results of the randomized phase IIB ARCTIC trial of low-dose rituximab in previously untreated CLL

Cited by 25 publications

References 24 publications

Clinical‐grade validation of whole genome sequencing reveals robust detection of low‐frequency variants and copy number alterations in CLL

Clinical‐grade validation of whole genome sequencing reveals robust detection of low‐frequency variants and copy number alterations in CLL

An Updated Perspective on Current Prognostic and Predictive Biomarkers in Chronic Lymphocytic Leukemia in the Context of Chemoimmunotherapy and Novel Targeted Therapy

Guideline for the treatment of chronic lymphocytic leukaemia

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