Prognostic risk score for patients with relapsed or refractory chronic lymphocytic leukaemia treated with targeted therapies or chemoimmunotherapy: a retrospective, pooled cohort study with external validations

Publication date: Available online 17 May 2019Source: The Lancet HaematologyAuthor(s): Jacob D Soumerai, Ai Ni, Mohamed Darif, Anil Londhe, Guan Xing, Yong Mun, Neil E Kay, Tait D Shanafelt, Kari G Rabe, John C Byrd, Asher A Chanan-Khan, Richard R Furman, Peter Hillmen, Jeffrey Jones, John F Seymour, Jeffrey P Sharman, Lucille Ferrante, Mehrdad Mobasher, Thomas Stark, Vijay ReddySummaryBackgroundClinically validated prognostic models for overall survival do not exist for patients with relapsed or refractory chronic lymphocytic leukaemia (CLL) who are on targeted therapies. We aimed to create a prognostic model to identify high-risk individuals who do not achieve a good outcome with available targeted therapies.MethodsIn this retrospective, pooled cohort study, 2475 patients with CLL treated between June 22, 2012, and Sept 23, 2015, in six randomised trials of ibrutinib, idelalisib, and venetoclax, or at the Mayo Clinic CLL Database (MCCD) were included. Eligible patients had CLL, were previously treated, were aged 18 years or older, had ECOG performance status 0–1, and required further treatment as per the international workshop on CLL 2008 criteria. There was heterogeneity in other eligibility criteria. We evaluated 28 candidate factors known to affect the overall survival of these patients and applied univariate and multivariate analyses to derive the risk score in a training dataset (n=727) of patients treated with ibrutinib or chemoimmunotherapy. We validated the sc...
Source: The Lancet Haematology - Category: Hematology Source Type: research

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Go online to PeerView.com/XAC860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, based on a recent live symposium held during the Oncology Nursing Society’s (ONS) 44th Annual Congress, a panel of expert nurse faculty use a MasterClass/case-forum design to offer an in-depth review of BTK inhibitors, their therapeutic applications in B-cell malignancies, and the core nurse-focused practice issues that are central to the further integration of BTK inhibitors into treatment plans for patients with cancers such as chronic lymphocytic leukemia (CLL) and ...
Source: PeerView CME/CE Audio Podcast - Pulmonology - Category: Respiratory Medicine Authors: Tags: Science, Medicine Source Type: podcasts
Go online to PeerView.com/EQY860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. This PeerView CME/CNE-certified activity—based on a live event conducted in a MasterClass format held in conjunction with the 2019 meeting of the AACR—discusses how Bruton tyrosine kinase (BTK) inhibitors effectively target aspects of B-cell receptor signaling and covers key evidence and clinical issues related to the use of BTK inhibitors in hematologic malignancies (including agent selection, potential combination regimens, and strategies for overcoming drug intolerance or resis...
Source: Peerview CME/CE Video Podcast - Internal Medicine International - Category: Internal Medicine Authors: Tags: Science, Medicine Source Type: video
354Background: Each year more than 90,000 cases of chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL) are expected in the US. The standard of care includes immuno-chemotherapy with alkylating agents in combination with an anti-CD20 monoclonal antibody, in addition to targeted therapies such as Bruton’s tyrosine kinase inhibitors. While immuno-chemotherapy regimens are initially effective in inducing responses, most patients inevitably relapse and the same therapies show decreasing efficacy with repeated administration. In recent years, CD37 has emerged as a new therapeutic target for B-cell malignancie...
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Oncology, Basic and Translational (Basic Science) III Source Type: research
Transformation of chronic lymphocytic leukaemia (CLL) to diffuse large B-cell lymphoma (DLCBL) type Richter ’s syndrome (RS) carries a dismal prognosis. Standard-of-care chemoimmunotherapy for de novo RS is ina...
Source: BMC Cancer - Category: Cancer & Oncology Authors: Tags: Study protocol Source Type: research
(H. Lee Moffitt Cancer Center&Research Institute) Researchers from Moffitt Cancer Center and Dana-Farber Cancer Institute have discovered a mechanism of drug resistance to Venetoclax ® , also known as ABT-199, a BCL-2 targeting drug commonly used to treat chronic lymphocytic leukemia and acute myeloid leukemia. Their findings, published in the journal Cancer Cell, also suggest a possible co-treatment strategy to overcome this resistance.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
Conclusions The clinical trials discussed here, which include several trials investigating novel therapeutic targets, demonstrate that translational research in pemphigus and pemphigoid is a fast-growing field. We thus expect that several novel treatments will be shortly available for the treatment of pemphigus and pemphigoid patients. Given the high, and thus far unmet, medical need in this field (110), this is highly encouraging and will hopefully improve the quality of life of the affected patients. In addition to the compounds and targets described here, several new targets have been recently identified in preclinical...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Antonio Lucena-Cacace1, Masayuki Umeda1, Lola E. Navas2,3 and Amancio Carnero2,3* 1Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan 2CIBERONC, ISCIII, Madrid, Spain 3Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío (HUVR), CSIC, Universidad de Sevilla, Sevilla, Spain Glioma Cancer Stem-Like Cells (GSCs) are a small subset of CD133+ cells with self-renewal properties and capable of initiating new tumors contributing to Glioma progression, maintenance, hierarchy, and complexity. GSCs are highly res...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Based on the recent revolution in the therapeutic landscape for hematological malignancies including B cell lymphomas, CART ‐CD19 cell therapy as a new therapeutic option for RS might be available in the coming years. It aims to reduce patient's tumor burden, prolong their survival time, and provide opportunities for other sequential therapy such as chemotherapy and bone marrow transplantation. AbstractRichter syndrome (RS) indicates the transformation of chronic lymphocytic leukemia (CLL) into an aggressive lymphoma (mostly DLBCL). Richter syndrome is a rare complication with an aggressive clinical course, bearing an un...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
Conclusion and Future Perspectives This review illustrates our current knowledge of USP7, including its source and characterization, structure, binding partners and substrates in various biological processes. Besides, how USP7 regulates various aspects of a cell under both normal and pathological states are elaborated in detail. As the processes of ubiquitination and deubiquitination are extremely dynamic and context-specific, a series of studies have linked USP7 to different cancers. The biology, particularly the immune oncology mechanisms, reveal that USP7 inhibitors would be useful drugs, thus it is vital to develop hi...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Alla S. Koltsova1,2, Anna A. Pendina1, Olga A. Efimova1*, Olga G. Chiryaeva1, Tatyana V. Kuznetzova1 and Vladislav S. Baranov1,2 1D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russia 2Department of Genetics and Biotechnology, Saint Petersburg State University, Saint Petersburg, Russia In the present review, we focus on the phenomenon of chromothripsis, a new type of complex chromosomal rearrangements. We discuss the challenges of chromothripsis detection and its distinction from other chromoanagenesis events. Along with already known causes and mechanisms, we introdu...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
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