Chronic lymphocytic leukemia: 2020 update on diagnosis, risk stratification and treatment
TLDR
Chronic lymphocytic leukemia (CLL), the commonest leukemia in western countries, typically occurs in elderly patients and has a highly variable clinical course.Abstract:
Disease overview Chronic lymphocytic leukemia (CLL) is the commonest leukemia in western countries. The disease typically occurs in elderly patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that impair apoptosis of clonal B-cells. Diagnosis The diagnosis is established by blood counts, blood smears, and immunophenotyping of circulating B-lymphocytes, which identify a clonal B-cell population carrying the CD5 antigen, as well as typical B-cell markers. Prognosis The two similar clinical staging systems, Rai and Binet, create prognostic information by using results of physical examination and blood counts. Various biological and genetic markers also have prognostic value. Deletions of the short arm of chromosome 17 (del [17p]) and/or mutations of the TP53 gene, predict resistance to chemoimmunotherapy and a shorter time to progression, with most targeted therapies. A comprehensive, international prognostic score (CLL-IPI) integrates genetic, biological and clinical variables to identify distinct risk groups of CLL patients. Therapy Only patients with active or symptomatic disease, or with advanced Binet or Rai stages require therapy. When treatment is indicated, several options exist for most CLL patients: a combination of venetoclax with obinutuzumab, ibrutinib monotherapy, or chemoimmunotherapy. For physically fit patients younger than 65 (in particular when presenting with a mutated IGVH gene), chemoimmunotherapy with fludarabine, cyclophosphamide and rituximab remains a standard therapy, since it may have curative potential. At relapse, the initial treatment may be repeated, if the treatment-free interval exceeds 3 years. If the disease relapses earlier, therapy should be changed using an alternative regimen. Patients with a del (17p) or TP53 mutation are a different, high-risk category and should be treated with targeted agents. An allogeneic SCT may be considered in relapsing patients with TP53 mutations or del (17p), or patients that are refractory to inhibitor therapy. Future challenges Targeted agents (ibrutinib, idelalisib, venetoclax, obinutuzumab) will be increasingly used in combination to allow for short, but potentially definitive therapies of CLL. It remains to be proven that they generate a superior outcome when compared to monotherapies with inhibitors of Bruton tyrosine kinase, which can also yield long-lasting remissions. Moreover, the optimal sequencing of drug combinations is unknown. Therefore, CLL patients should be treated in clinical trials whenever possible.read more
Citations
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Journal ArticleDOI
Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial
Jeff P. Sharman,Miklos Egyed,Wojciech Jurczak,Alan P Skarbnik,Alan P Skarbnik,John M. Pagel,Ian W. Flinn,Manali Kamdar,Talha Munir,Renata Walewska,Gillian Corbett,Laura Fogliatto,Yair Herishanu,Versha Banerji,Steven Coutre,George A Follows,Patricia F. Walker,Karin Karlsson,Paolo Ghia,Ann Janssens,Florence Cymbalista,Jennifer A. Woyach,Gilles Salles,William G. Wierda,Raquel Izumi,Veerendra Munugalavadla,Priti Patel,Min Hui Wang,Sofia Wong,John C. Byrd +29 more
TL;DR: The primary endpoint was progression-free survival between the two combination-therapy groups, assessed by independent review committee.
Journal ArticleDOI
TNMplot.com: A Web Tool for the Comparison of Gene Expression in Normal, Tumor and Metastatic Tissues.
Áron Bartha,Balázs Győrffy +1 more
TL;DR: In this article, the authors established an integrated database using available transcriptome-level datasets and created a web platform which enables the mining of this database by comparing normal, tumor and metastatic data across all genes in real time.
Posted ContentDOI
TNMplot.com: a web tool for the comparison of gene expression in normal, tumor and metastatic tissues
Aron Bartha,Balazs Gyorffy +1 more
TL;DR: An integrated database using available transcriptome-level datasets and a web-platform enabling mining of this database by comparing normal, tumor and metastatic data across all genes in real time are established.
Journal ArticleDOI
The phase 3 DUO trial: duvelisib vs ofatumumab in relapsed and refractory CLL/SLL
Ian W. Flinn,Peter Hillmen,Marco Montillo,Zsolt Nagy,Árpád Illés,Gabriel Etienne,Julio Delgado,Bryone J. Kuss,Constantine S. Tam,Zoltán Gasztonyi,Fritz Offner,Scott D. Lunin,Francesco Bosch,Matthew S. Davids,Nicole Lamanna,Ulrich Jaeger,Paolo Ghia,Florence Cymbalista,Craig A. Portell,Alan P Skarbnik,Amanda F. Cashen,David T. Weaver,Virginia Kelly,Barry Turnbull,Stephan Stilgenbauer +24 more
TL;DR: The DUO trial data support duvelisib as a potentially effective treatment option for patients with relapsed or refractory (RR) CLL/SLL and the overall response rate was significantly higher with duvel isib regardless of del(17p) status.
Journal ArticleDOI
ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia
Paolo Ghia,Andrzej Pluta,Malgorzata Wach,Daniel Lysák,Tomas Kozak,Martin Simkovic,Polina Kaplan,Iryna Kraychok,Árpád Illés,Javier de la Serna,Sean Dolan,Phillip L. Campbell,Gerardo Musuraca,Abraham Jacob,Eric J. Avery,Jae Hoon Lee,Wei Liang,Priti Patel,Cheng Quah,Wojciech Jurczak +19 more
TL;DR: Acalabrutinib significantly improved PFS compared with I-R or B-R and has an acceptable safety profile in patients with R/R CLL.
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