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https://www.readbyqxmd.com/read/28336937/results-of-the-randomized-phase-iib-arctic-trial-of-low-dose-rituximab-in-previously-untreated-cll
#1
D R Howard, T Munir, L McParland, A C Rawstron, D Milligan, A Schuh, A Hockaday, D J Allsup, S Marshall, A S Duncombe, J L O'Dwyer, A F Smith, R Longo, A Varghese, P Hillmen
ARCTIC was a multi-center, randomized-controlled, open, phase IIB non-inferiority trial in previously untreated Chronic Lymphocytic Leukemia (CLL). Conventional frontline therapy in fit patients is fludarabine, cyclophosphamide and rituximab (FCR). The trial hypothesized that including mitoxantrone with low-dose rituximab (FCM-miniR) would be non-inferior to FCR. 200 patients were recruited to assess the primary endpoint of complete remission (CR) rates according to IWCLL criteria. Secondary endpoints were progression-free survival (PFS), overall survival (OS), overall response rate, minimal residual disease (MRD) negativity, safety and cost-effectiveness...
March 24, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28331288/development-of-venetoclax-for-therapy-of-lymphoid-malignancies
#2
REVIEW
Huayuan Zhu, Alexandru Almasan
B-cell lymphoma-2 (BCL-2) family dysfunction and impairment of apoptosis are common in most B-cell lymphoid malignancies. Venetoclax (Venclexta™, formerly ABT-199, GDC-0199) is a highly selective BCL-2 inhibitor, which mimics its BCL-2 homology 3-domain to induce apoptosis. It was approved for treatment of previously treated chronic lymphocytic leukemia (CLL) patients with 17p deletion early in 2016. It has also been in clinical trials for other B-cell lymphoid malignancies. Unlike the other recently approved targeted agents idelalisib and ibrutinib, so far there has been no relapse reported in some patients...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28324286/prolymphocytic-leukemia-new-insights-in-diagnosis-and-in-treatment
#3
REVIEW
Aude Collignon, Anne Wanquet, Elsa Maitre, Edouard Cornet, Xavier Troussard, Thérèse Aurran-Schleinitz
PURPOSE OF REVIEW: We aimed to produce a comprehensive update on clinical and biological data regarding two rare lymphoid neoplasms, B and T prolymphocytic leukemias, and assess therapeutic management in the light of new molecular insights and the advent of targeted therapies. RECENT FINDINGS: B cell prolymphocytic leukemia (B-PLL) diagnosis remains challenging in the absence of clear immunophenotypic or cytogenetic signature and overlap with mantle cell lymphoma...
April 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28303898/circulating-tumour-dna-reflects-treatment-response-and-clonal-evolution-in-chronic-lymphocytic-leukaemia
#4
Paul Yeh, Tane Hunter, Devbarna Sinha, Sarah Ftouni, Elise Wallach, Damian Jiang, Yih-Chih Chan, Stephen Q Wong, Maria Joao Silva, Ravikiran Vedururu, Kenneth Doig, Enid Lam, Gisela Mir Arnau, Timothy Semple, Meaghan Wall, Andjelija Zivanovic, Rishu Agarwal, Pasquale Petrone, Kate Jones, David Westerman, Piers Blombery, John F Seymour, Anthony T Papenfuss, Mark A Dawson, Constantine S Tam, Sarah-Jane Dawson
Several novel therapeutics are poised to change the natural history of chronic lymphocytic leukaemia (CLL) and the increasing use of these therapies has highlighted limitations of traditional disease monitoring methods. Here we demonstrate that circulating tumour DNA (ctDNA) is readily detectable in patients with CLL. Importantly, ctDNA does not simply mirror the genomic information contained within circulating malignant lymphocytes but instead parallels changes across different disease compartments following treatment with novel therapies...
March 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28302090/characterizing-and-prognosticating-chronic-lymphocytic-leukemia-in-the-elderly-prospective-evaluation-on-455-patients-treated-in-the-united-states
#5
Chadi Nabhan, Anthony Mato, Christopher R Flowers, David L Grinblatt, Nicole Lamanna, Mark A Weiss, Matthew S Davids, Arlene S Swern, Shriya Bhushan, Kristen Sullivan, E Dawn Flick, Pavel Kiselev, Jeff P Sharman
BACKGROUND: Median age at diagnosis of patients with chronic lymphocytic leukemia (CLL) is > 70 years. However, the majority of clinical trials do not reflect the demographics of CLL patients treated in the community. We examined treatment patterns, outcomes, and disease-related mortality in patients ≥ 75 years with CLL (E-CLL) in a real-world setting. METHODS: The Connect® CLL registry is a multicenter, prospective observational cohort study, which enrolled 1494 adult patients between 2010-2014, at 199 US sites...
March 16, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28299881/the-regulation-of-tumor-suppressive-microrna-mir-126-in%C3%A2-chronic-lymphocytic-leukemia
#6
Daphne Guinn, Amy Lehman, Catherine Fabian, Lianbo Yu, Kami Maddocks, Leslie A Andritsos, Jeffrey A Jones, Joseph M Flynn, Samantha M Jaglowski, Jennifer A Woyach, John C Byrd, Amy J Johnson
The introduction of miR profiling of chronic lymphocytic leukemia (CLL) patients with different cytogenetic profiles and responses to therapy has allowed incorporation of important miR-mRNA interactions into the understanding of disease biology. In this study, we performed miR expression analysis using NanoString nCounter to discover differentially regulated miRs after therapy with the Bruton tyrosine kinase inhibitor ibrutinib. Of the differentially regulated miRs in the discovery set, miR-29c and miR-126 were confirmed using real-time PCR to be upregulated in CLL patient cells with ibrutinib therapy...
March 15, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28297623/clinical-implications-of-novel-genomic-discoveries-in-chronic-lymphocytic-leukemia
#7
Gregory Lazarian, Romain Guièze, Catherine J Wu
Chronic lymphocytic leukemia (CLL) is a common B-cell malignancy with a remarkably heterogeneous course, ranging from indolent disease with no need for immediate therapy to rapidly progressive disease associated with therapeutic resistance. The recent US Food and Drug Administration approvals of novel targeted therapies such as inhibitors of B-cell receptor signaling and B-cell lymphoma 2 have opened up new opportunities in the clinical management of patients with CLL and heralded a new era in the clinical treatment of this disease...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28295729/targeting-of-b-cell-receptor-signalling-in-b-cell-malignancies
#8
M Jerkeman, M Hallek, M Dreyling, C Thieblemont, E Kimby, L Staudt
Pharmacological agents that inhibit enzymes of the B-cell receptor (BCR) pathway are of increasing importance in the treatment of B-cell malignancies. These include inhibitors of Bruton tyrosine kinase (BTK), phosphatidylinositol 3-kinase (PI3K), splenic tyrosine kinase and protein kinase Cβ. Two agents are already approved in the USA and Europe: ibrutinib, a BTK inhibitor, for the treatment of chronic lymphatic leukaemia (CLL), mantle cell lymphoma (MCL) and Waldenström's macroglobulinemia; and idelalisib, a PI3Kδ inhibitor, for the treatment of CLL and follicular lymphoma...
March 14, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28282218/immunotoxins-in-cancer-therapy-review-and-update
#9
Bahman Akbari, Safar Farajnia, Shiva Ahdi Khosroshahi, Fatemeh Safari, Mohammadreza Yousefi, Hassan Dariushnejad, Leila Rahbarnia
Immunotoxins are a novel class of cancer therapeutics that contains a cytotoxic agent fused to a targeting moiety. Various toxic agents from different sources are used in immunotoxin development, including bacterial, plant and human origin cytotoxic elements. Although bacterial and plant-derived toxins are highly toxic and commonly used in immunotoxins, their immunogenicity for human restricted their application in cancer therapy. Here, we discuss the advantages and limitations of bacterial toxins such as Pseudomonas and Diphtheria toxins, plant toxins such as ricin and gelonin, and some endogenous protein of human origin such as RNases and Granzymes...
March 1, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28275912/mechanisms-of-resistance-to-targeted-therapies-in-chronic-lymphocytic-leukemia
#10
Francesca Arruga, Silvia Deaglio
Even if treatment options for Chronic Lymphocytic Leukemia (CLL) patients have changed dramatically in the past few years, with the approval of targeted therapeutic agents, the disease remains incurable. Beside intrinsic genetic features characterizing the leukemic cell, signals coming from the microenvironment have a key role in promoting cell survival and in protecting CLL cells from the action of drugs. Consequently, the identification of previously unrecognized genetic lesions is important in risk-stratification of CLL patients and is progressively becoming a critical tool for choosing the best therapeutic strategy...
March 9, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28271950/novel-agents-versus-chemotherapy-as-frontline-treatment-of-cll
#11
Anna Piggin, Emma Bayly, Constantine S Tam
Chronic lymphocytic leukemia (CLL) is a neoplastic disorder of mature B lymphocytes. While traditionally treated with combinations of chemoimmunotherapy, the therapeutic options for CLL have expanded in recent years with the emergence of novel oral agents, such as the Bruton tyrosine kinase inhibitor ibrutinib, that are well tolerated and highly efficacious. The role of novel agents in the first-line setting is now being investigated in head-to-head clinical trials. In this discussion paper, we consider the role of novel agents in the up-front setting, using three case studies of treatment-naive patients to highlight how choice of therapy may be individualized depending on the characteristics of the patient and the disease, as well as patient preferences...
June 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28257957/the-cancer-immunity-cycle-as-rational-design-for-synthetic-cancer-drugs-novel-dc-vaccines-and-car-t-cells
#12
REVIEW
Mohanraj Ramachandran, Anna Dimberg, Magnus Essand
Cell therapy is an advanced form of cancer immunotherapy that has had remarkable clinical progress in the past decade in the search for cure of cancer. Most success has been achieved for chimeric antigen receptor (CAR) T-cells where CAR T-cells targeting CD19 show very high complete response rates for patients with refractory acute B-cell acute lymphoblastic leukemia (ALL) and are close to approval for this indication. CD19 CAR T-cells are also effective against B-cell chronic lymphoblastic leukemia (CLL) and B-cell lymphomas...
February 28, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28257752/efficacy-and-safety-of-idelalisib-in-combination-with-ofatumumab-for-previously-treated-chronic-lymphocytic-leukaemia-an-open-label-randomised-phase-3-trial
#13
Jeffrey A Jones, Tadeusz Robak, Jennifer R Brown, Farrukh T Awan, Xavier Badoux, Steven Coutre, Javier Loscertales, Kerry Taylor, Elisabeth Vandenberghe, Malgorzata Wach, Nina Wagner-Johnston, Loic Ysebaert, Lyndah Dreiling, Ronald Dubowy, Guan Xing, Ian W Flinn, Carolyn Owen
BACKGROUND: Idelalisib, a selective inhibitor of PI3Kδ, is approved for the treatment of patients with relapsed chronic lymphocytic leukaemia (CLL) in combination with rituximab. We aimed to assess the efficacy and safety of idelalisib in combination with a second-generation anti-CD20 antibody, ofatumumab, in a similar patient population. METHODS: In this global, open-label, randomised, controlled phase 3 trial, we enrolled patients with relapsed CLL progressing less than 24 months from last therapy...
March 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28246553/the-role-of-combined-fludarabine-cyclophosphamide-and-rituximab-chemoimmunotherapy-in-chronic-lymphocytic-leukemia-current-evidence-and-controversies
#14
REVIEW
Alan P Skarbnik, Stefan Faderl
Chemoimmunotherapy (CIT) has become a cornerstone in the treatment of patients with chronic lymphocytic leukemia (CLL). The combination of fludarabine, cyclophosphamide and rituximab (FCR) has emerged as the standard of care for therapy of previously untreated patients with CLL who are younger than 65 years and have no significant comorbidities. In this article, we review the role of FCR in the current treatment paradigm for CLL.
March 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28245413/-research-progress-in-transgenic-animal-models-of-chronic-lymphocytic-leukemia-review
#15
Fang-Tian Wu, Wei Xu, Jian-Yong Li
Transgenic mouse models of chronic lymphocytic leukemia (CLL) are crucially required for the elucidation of the underlying pathogenic mechanisms and for finding new therapies. So far, several mouse models have been established, mimicking either genetic aberrations or dysregulated gene expression in CLL. Among all the models, TCL1 transgenic model is the most commonly used one. Additionally, there are also other models, such as 13q14-deletion model. In this review, the major genetically engineered mouse models of CLL in current use are summarized, the main problems include TCL-1 transgenic mice, miR15a/16-1 gene knockdown mice and miR29 transgeneic mice, BAFF and APRIL transgeneic mice, BCL-2:Traf2DN double transgeneic mice, IRF4(-/-)Vh11 transgeneic mice and so on...
February 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28245410/-research-progress-of-novel-small-molecule-drugs-in-the-treatment-of-chronic-lymphocytic-leukemia-review
#16
Jing-Qiao Qiao, Miao He, Shu-Ting Zhang, Hai Bai
Chronic lymphocytic leukemia (CLL), the most frequent adult leukemia in Western population, is characterized by accumulation of mature-looking CD5(+)/19(+)/23(+) B cells in peripheral blood, bone marrow, and lymphatic organs. Over the last 20 years, there has been a dramatic change in therapy for CLL, the complete response rate increased from the initial <5% to the current 40%-50%, this remarkable improvement has been attributable to combination of chemoimmunotherapy agents that have contributed to the backbone of therapy for patients with CLL...
February 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28243993/what-is-optimal-front-line-therapy-for-chronic-lymphocytic-leukemia-in-2017
#17
REVIEW
Benjamin N Voorhies, Deborah M Stephens
The front-line management of patients with chronic lymphocytic leukemia (CLL) has evolved significantly in recent years due to introduction of novel, targeted agents. Upon CLL diagnosis, physicians should determine whether treatment or careful observation is indicated. Once treatment is required, choice of therapy should be based on the age and fitness of the patient and the distinct molecular profile of their disease. As multiple novel agents are in various stages of development, all patients regardless of their age, fitness, and disease risk should be evaluated for clinical trial participation before initiating any front-line therapy...
February 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28223822/profile-of-venetoclax-and-its-potential-in-the-context-of-treatment-of-relapsed-or-refractory-chronic-lymphocytic-leukemia
#18
REVIEW
Henriette Huber, Simone Edenhofer, Sven Estenfelder, Stephan Stilgenbauer
Over the last few years, dramatic changes have occurred in the treatment of chronic lymphocytic leukemia (CLL). The current standard for young and fit patients with CLL remains chemoimmunotherapy, namely the fludarabine, cyclophosphamide, and rituximab (FCR) regimen. However, novel oral therapies are presently being introduced and represent a considerable breakthrough concerning effectiveness and safety profile. In particular, the very high-risk group of CLL patients, defined by the genetic aberration del(17p) and/or TP53 mutation, benefit from the new agents...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28220479/a-phase-1-2-trial-of-ublituximab-a-novel-anti-cd20-monoclonal-antibody-in-patients-with-b-cell-non-hodgkin-lymphoma-or-chronic-lymphocytic-leukaemia-previously-exposed-to-rituximab
#19
Ahmed Sawas, Charles M Farber, Marshall T Schreeder, Mazen Y Khalil, Daruka Mahadevan, Changchun Deng, Jennifer E Amengual, Petros G Nikolinakos, Jill M Kolesar, John G Kuhn, Peter Sportelli, Hari P Miskin, Owen A O'Connor
This phase 1/2 study evaluated the safety, pharmacokinetic behavior and anti-tumour activity of ublituximab, a unique type I, chimeric, glycoengineered anti-CD20 monoclonal antibody, in rituximab-relapsed or -refractory patients with B-cell non-Hodgkin lymphoma (B-NHL) or chronic lymphocytic leukaemia (CLL). Induction therapy (doses of 450-1200 mg) consisted of 4 weekly infusions in cycle 1 for NHL and 3 weekly infusions in cycles 1 and 2 for CLL. Patients received ublituximab maintenance monthly during cycles 3-5, then once every 3 months for up to 2 years...
February 21, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28216660/results-of-the-randomized-phase-iib-admire-trial-of-fcr-with-or-without-mitoxantrone-in-previously-untreated-cll
#20
T Munir, D R Howard, L McParland, C Pocock, A C Rawstron, A Hockaday, A Varghese, M Hamblin, A Bloor, A Pettitt, C Fegan, J Blundell, J G Gribben, D Phillips, P Hillmen
ADMIRE was a multi-center, randomized-controlled, open, phase IIB superiority trial in previously untreated Chronic Lymphocytic Leukemia (CLL). Conventional frontline therapy in fit patients is fludarabine, cyclophosphamide and rituximab (FCR). Initial evidence from non-randomized Phase II trials suggested that the addition of mitoxantrone to FCR (FCM-R) improved remission rates. 215 patients were recruited to assess the primary endpoint of complete remission (CR) rates according to IWCLL criteria. Secondary endpoints were progression-free survival (PFS), overall survival (OS), overall response rate, minimal residual disease (MRD) negativity and safety...
February 20, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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