Biology and Treatment of High-Risk CLL

  • 18k

    Total downloads

  • 67k

    Total views and downloads

Download PDFDownload EPUB

About this Research Topic

Submission closed

Background

In the era of chemoimmunotherapy, treatment options were limited for patients with primary high-risk chronic lymphocytic leukemia (CLL), as defined by the presence of TP53 loss and/or mutation. The development of targeted therapy approaches has changed paradigms in CLL treatment fundamentally and enriched opportunities for primary high risk and purine-analogue refractory CLL as well as for CLL patients with an early relapse after chemoimmunotherapy. At present, BTK-inhibitors such as ibrutinib or acalabrutinib and the BCL2-inhibitor venetoclax in combination with obinutuzumab or rituximab have almost completely replaced chemoimmunotherapy with fludarabine/cyclophosphamide/rituximab (FCR) or bendamustine/rituximab (BR) in 1st- and 2nd-line CLL treatment. Pi3K inhibitors such as idelalisib lost their role in front line treatment due to an unfavorable safety profile but remain an alternative for 3rd line. Due to this wider range of approved drugs and novel compounds available in clinical trials, identifying patients and timepoints for allogeneic stem cell transplantation has become a difficult task in CLL treatment, which is further challenged by the availability of alternative cellular treatment strategies based on CAR-T- and CAR-NK-cell products.

Although the switch to chemo-free treatment regimens significantly improved the prognosis of TP53 deficient patients, response rates and survival remain behind those observed in standard-risk CLL. Other biologic markers conferring refractoriness or early treatment failure have yet not clearly been defined, but markers under investigation are the presence of a complex karyotype, gain of the MYC gene locus, mutation of NOTCH1, and the presence of defined subsets of stereotyped B-cell receptors. The presence of TP53 deficiency, MYC gain, NOTCH1 mutation, and loss of the CDKN2A/B gene loci were also identified as hallmark genomic alterations in Richter transformation, which is the transformation of CLL into aggressive lymphoma, often having a dismal prognosis due to a lack of established treatment options.

Only a profound understanding of biomarkers predicting non benefit from standardized treatment protocols will enable a personalized approach to tailor best effective and cost saving drug combinations for each CLL patient. While the identification of biomarkers in the past mainly focused on genomic analyses, the characterization of tumors has nowadays become more comprehensive by the application of “omic” technologies allowing an integrative analysis of genomic, epigenomic, transcriptomic, proteomic and metabolomic data. Furthermore, an improved understanding of the CLL microenvironment can promote better incorporation of immune modulatory approaches into treatment concepts. Given this complexity, comprehensive analyses taking all aspects into account will necessitate the development of large-scale databases.

The scope of the proposed article series on “Treatment and Characteristics of High risk CLL” is to discuss the definition of high risk CLL in a changing treatment landscape and to provide a state-of-the-art overview by invited review articles on targeted and immunotherapeutic treatment options and on biologic markers associated with high risk disease character. Building up on the contemporary view provided, original research articles will add novel clinical, translational and biological data to the field and perspectives will discuss how to further refine the definition of high risk CLL and optimize treatment designs for high-risk CLL and Richter transformation.

Keywords: CLL, TP53, biomarkers, targeted therapy, immunotherapy

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Topic editors

Frequently asked questions

  • Frontiers' Research Topics are collaborative hubs built around an emerging theme.Defined, managed, and led by renowned researchers, they bring communities together around a shared area of interest to stimulate collaboration and innovation.

    Unlike section journals, which serve established specialty communities, Research Topics are pioneer hubs, responding to the evolving scientific landscape and catering to new communities.

  • The goal of Frontiers' publishing program is to empower research communities to actively steer the course of scientific publishing. Our program was implemented as a three-part unit with fixed field journals, flexible specialty sections, and dynamically emerging Research Topics, connecting communities of different sizes and maturity.

    Research Topics originate from the scientific community. Many of our Research Topics are suggested by existing editorial board members who have identified critical challenges or areas of interest in their field.

  • As an editor, Research Topics will help you build your journal, as well as your community, around emerging, cutting-edge research. As research trailblazers, Research Topics attract high-quality submissions from leading experts all over the world.

    A thriving Research Topic can potentially evolve into a new specialty section if there is sustained interest and a growing community around it.

  • Each Research Topic must be approved by the specialty chief editor, and it falls under the editorial oversight of our editorial boards, supported by our in-house research integrity team. The same standards and rigorous peer review processes apply to articles published as part of a Research Topic as for any other article we publish.

    In 2023, 80% of the Research Topics we published were edited or co-edited by our editorial board members, who are already familiar with their journal's scope, ethos, and publishing model. All other topics are guest edited by leaders in their field, each vetted and formally approved by the specialty chief editor.

  • Publishing your article within a Research Topic with other related articles increases its discoverability and visibility, which can lead to more views, downloads, and citations. Research Topics grow dynamically as more published articles are added, causing frequent revisiting, and further visibility.

    As Research Topics are multidisciplinary, they are cross-listed in several fields and section journals – increasing your reach even more and giving you the chance to expand your network and collaborate with researchers in different fields, all focusing on expanding knowledge around the same important topic.

    Our larger Research Topics are also converted into ebooks and receive social media promotion from our digital marketing team.

     

  • Frontiers offers multiple article types, but it will depend on the field and section journals in which the Research Topic will be featured. The available article types for a Research Topic will appear in the drop-down menu during the submission process.

    Check available article types here 

  • Yes, we would love to hear your ideas for a topic. Most of our Research Topics are community-led and suggested by researchers in the field. Our in-house editorial team will contact you to talk about your idea and whether you’d like to edit the topic. If you’re an early-stage researcher, we will offer you the opportunity to coordinate your topic, with the support of a senior researcher as the topic editor. 

    Suggest your topic here 

  • A team of guest editors (called topic editors) lead their Research Topic. This editorial team oversees the entire process, from the initial topic proposal to calls for participation, the peer review, and final publications.

    The team may also include topic coordinators, who help the topic editors send calls for participation, liaise with topic editors on abstracts, and support contributing authors. In some cases, they can also be assigned as reviewers.

  • As a topic editor (TE), you will take the lead on all editorial decisions for the Research Topic, starting with defining its scope. This allows you to curate research around a topic that interests you, bring together different perspectives from leading researchers across different fields and shape the future of your field. 

     

    You will choose your team of co-editors, curate a list of potential authors, send calls for participation and oversee the peer review process, accepting or recommending rejection for each manuscript submitted.

  • As a topic editor, you're supported at every stage by our in-house team. You will be assigned a single point of contact to help you on both editorial and technical matters. Your topic is managed through our user-friendly online platform, and the peer review process is supported by our industry-first AI review assistant (AIRA).

  • If you’re an early-stage researcher, we will offer you the opportunity to coordinate your topic, with the support of a senior researcher as the topic editor. This provides you with valuable editorial experience, improving your ability to critically evaluate research articles and enhancing your understanding of the quality standards and requirements for scientific publishing, as well as the opportunity to discover new research in your field, and expand your professional network.

  • Yes, certificates can be issued on request. We are happy to provide a certificate for your contribution to editing a successful Research Topic.

  • Research Topics thrive on collaboration and their multi-disciplinary approach around emerging, cutting-edge themes, attract leading researchers from all over the world.

  • As a topic editor, you can set the timeline for your Research Topic, and we will work with you at your pace. Typically, Research Topics are online and open for submissions within a few weeks and remain open for participation for 6 – 12 months. Individual articles within a Research Topic are published as soon as they are ready.

    Find out more about our Research Topics

  • Our fee support program ensures that all articles that pass peer review, including those published in Research Topics, can benefit from open access – regardless of the author's field or funding situation.

    Authors and institutions with insufficient funding can apply for a discount on their publishing fees. A fee support application form is available on our website.

  • In line with our mission to promote healthy lives on a healthy planet, we do not provide printed materials. All our articles and ebooks are available under a CC-BY license, so you can share and print copies.

     

Impact

  • 67kTopic views
  • 47kArticle views
  • 18kArticle downloads
View impact