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https://www.readbyqxmd.com/read/28811872/current-and-emerging-treatment-options-for-mantle-cell-lymphoma
#1
REVIEW
Bita Fakhri, Brad Kahl
Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma with typically aggressive behavior. The genetic signature is the chromosomal translocation t(11;14)(q13;q32) resulting in overexpression of cyclin D1. Asymptomatic newly diagnosed MCL patients with low tumor burden can be closely observed, deferring therapy to the time of disease progression. Although MCL classically responds to upfront chemotherapy, it remains incurable with standard approaches. For patients in need of frontline therapy, the initial decision is whether to proceed with an intensive treatment strategy or a non-intensive treatment strategy...
August 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28808046/car-t-cells-drive-cll-remissions
#2
(no author information available yet)
A new study shows that chimeric antigen receptor T cells produce objective responses in 71% of patients with chronic lymphocytic leukemia whose disease progressed despite receiving ibrutinib or who are unable to tolerate the drug. Cancer cells were undetectable in the bone marrow in 81% of tested patients, and 64% of tested patients showed complete lymph node responses. Most patients experienced adverse effects, however.
August 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28801451/adult-high-grade-b-cell-lymphoma-with-burkitt-lymphoma-signature-genomic-features-and-potential-therapeutic-targets
#3
Alyssa Bouska, Chengfeng Bi, Waseem Lone, Weiwei Zhang, Ambreen Kedwaii, Tayla Heavican, Cynthia M Lachel, Jiayu Yu, Roberto Ferro, Nanees Eldorghamy, Timothy C Greiner, Julie Vose, Dennis D Weisenburger, Randy D Gascoyne, Andreas Rosenwald, German Ott, Elias Campo, Lisa M Rimsza, Elaine S Jaffe, Rita M Braziel, Reiner Siebert, Rodney R Miles, Sandeep Dave, Anupama Reddy, Jan Delabie, Louis M Staudt, Joo Y Song, Timothy W McKeithan, Kai Fu, Michael Green, Wing C Chan, Javeed Iqbal
The adult high-grade B-cell lymphomas sharing molecular features with Burkitt lymphoma (BL) are highly aggressive lymphomas with poor clinical outcome. High-resolution structural and functional genomic analysis of adult Burkitt lymphoma (BL) and high-grade B-cell lymphoma with BL gene-signature (adult-mBL), revealed the MYC-ARF-p53 axis as the primary deregulated pathway. Adult-mBL had either unique or more frequent genomic aberrations (del13q14, del17p, gain8q24 and gain18q21) compared with pediatric-mBL, but shared commonly mutated genes...
August 11, 2017: Blood
https://www.readbyqxmd.com/read/28798070/cxcl13-levels-are-elevated-in-patients-with-waldenstrom-s-macroglobulinemia-and-are-predictive-of-major-response-to-ibrutinib
#4
Josephine M Vos, Nickolas Tsakmaklis, Christopher J Patterson, Kirsten Meid, Jorge J Castillo, Philip Brodsky, Tomas Ganz, Steven T Pals, Marie José Kersten, Lian Xu, Guang Yang, Steven P Treon, Zachary R Hunter
No abstract text is available yet for this article.
August 10, 2017: Haematologica
https://www.readbyqxmd.com/read/28796569/cost-effectiveness-of-kinase-inhibitors-for-hematologic-malignancies-a-systematic-and-critical-review
#5
Monia Marchetti
Several genetic disruptions lead to constitutive activation of those kinases leukemic cells depend on for survival and proliferation. Kinase inhibitors (KI) are major therapeutic innovations for chronic myeloid leukemia (CML), chronic lymphoid leukemia (CLL) and myelofibrosis (MF) providing a relevant improvement of quality-adjusted survival in patients with high-risk or refractory disease. CML patients are being treated with first-generation KI imatinib since many years, achieving expected survivals longer than 10 years...
August 10, 2017: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/28794071/a-multi-institutional-outcomes-analysis-of-patients-with-relapsed-or-refractory-dlbcl-treated-with-ibrutinib
#6
Allison M Winter, Daniel J Landsburg, Anthony R Mato, Krista Isaac, Francisco J Hernandez-Ilizaliturri, Nishitha Reddy, Stephen Smith, Mazyar Shadman, Mitchell R Smith, Paolo Caimi, Deepa Jagadeesh, Brian T Hill
No abstract text is available yet for this article.
August 9, 2017: Blood
https://www.readbyqxmd.com/read/28791187/ibrutinib-treatment-of-mantle-cell-lymphoma-relapsing-at-central-nervous-system-a-case-report-and-literature-review
#7
Donato Mannina, Barbara Loteta
Mantle cell lymphoma (MCL) accounts for about 5% of all lymphomas. Its clinical and histological features are heterogeneous. After a frequently good initial response, the disease generally and repeatedly relapses and finally the outcome is poor. Particularly severe is the prognosis of the rare occurrence of CNSi (Central Nervous System involvement). Ibrutinib, an oral inhibitor of Bruton tyrosine kinase (BTK), has shown strong activity in relapsing patients with Chronic Lymphocytic Leukemia (CLL) and MCL. Few reports are available about treatment with ibrutinib of patients presenting CNSi by lymphoproliferative diseases (LPD)...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28786474/dexamethasone-rituximab-and-cyclophosphamide-for-relapsed%C3%A2-and-or-refractory-and-treatment-na%C3%A3-ve-patients-with-waldenstrom-macroglobulinemia
#8
Jonas Paludo, Jithma P Abeykoon, Shaji Kumar, Amanda Shreders, Sikander Ailawadhi, Morie A Gertz, Taxiarchis Kourelis, Rebecca L King, Craig B Reeder, Nelson Leung, Robert A Kyle, Francis K Buadi, Thomas M Habermann, David Dingli, Thomas E Witzig, Angela Dispenzieri, Martha Q Lacy, Ronald S Go, Yi Lin, Wilson I Gonsalves, Rahma Warsame, John A Lust, S Vincent Rajkumar, Stephen M Ansell, Prashant Kapoor
The management of Waldenström macroglobulinaemia (WM) relies predominantly on small trials, one of which has demonstrated activity of dexamethasone, rituximab and cyclophosphamide (DRC) in the frontline setting. We report on the efficacy of DRC, focusing on relapsed/refractory (R/R) patients. Ibrutinib, a recently approved agent in WM demonstrated limited activity in patients with MYD88(WT) genotype. Herein, we additionally report on the activity of DRC based on the MYD88(L265P) mutation status. Of 100 WM patients evaluated between January 2007 and December 2014 who received DRC, 50 had R/R WM...
August 8, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28782884/chronic-lymphocytic-leukemia-2017-update-on-diagnosis-risk-stratification-and-treatment
#9
REVIEW
Michael Hallek
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 and B-cell markers...
September 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28780145/what-is-the-role-of-chemotherapy-in-patients-with-chronic-lymphocytic-leukemia
#10
REVIEW
Bruce D Cheson
The current standard treatment for patients with chronic lymphocytic leukemia who require therapy is chemoimmunotherapy. However, the availability of an increasing number of targeted agents and combination warrants a reassessment of that approach. The high rate of durable responses with ibrutinib in relapsed refractory patients has established its role in this setting; however, because of its impressive efficacy as initial treatment, it should be considered as part of the algorithm in appropriate patients. There is virtually no role for chemotherapy in the relapsed or refractory setting, but, instead, consideration of active agents including idelalisib plus rituximab, or, particularly venetoclax...
July 12, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28779053/the-%C3%AE-secretase-inhibitors-enhance-the-anti-leukemic-activity-of-ibrutinib-in-b-cll-cells
#11
Paola Secchiero, Rebecca Voltan, Erika Rimondi, Elisabetta Melloni, Emmanouil Athanasakis, Veronica Tisato, Stefania Gallo, Gian Matteo Rigolin, Giorgio Zauli
Ibrutinib blocks B-cell receptor signaling and interferes with leukemic cell-to-microenvironment interactions. Ibrutinib plays a key role in the management of B-CLL and is recommended for first line treatment of high-risk CLL patients with 17p deletion. Therefore, elucidating the factors governing sensitivity/resistance to Ibrutinib represents a relevant issue. For this purpose, in 3 B-CLL patient samples harboring functional TP53 mutations, the frequency of the mutated clones was monitored during in vivo Ibrutinib therapy, revealing a progressive decline of the frequency of TP53mut clones during 12 months of treatment...
July 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28775119/incidence-and-management-of-toxicity-associated-with-ibrutinib-and-idelalisib-a-practical-approach
#12
Iris de Weerdt, Suzanne M Koopmans, Arnon P Kater, Michel van Gelder
The use of novel B cell receptor signaling inhibitors results in high response rates and long progression-free survival in patients with indolent B cell malignancies, such as chronic lymphocytic leukemia, follicular lymphoma, mantle cell lymphoma and Waldenstroms macroglobulinemia. Ibrutinib, the first-in-class inhibitor or Bruton's tyrosine kinase, and idelalisib, the first-in-class inhibitor of phosphatidylinositol 3-kinase δ have recently been approved for several indolent B cell malignancies. These drugs especially foresee in previously unmet needs for patients with relapsed or refractory disease, high-risk cytogenetic or molecular abnormalities or with comorbidities...
August 3, 2017: Haematologica
https://www.readbyqxmd.com/read/28771673/activity-of-lenalidomide-in-mantle-cell-lymphoma-can-be-explained-by-nk-cell-mediated-cytotoxicity
#13
Patrick R Hagner, Hsiling Chiu, Maria Ortiz, Benedetta Apollonio, Maria Wang, Suzana Couto, Michelle F Waldman, Erin Flynt, Alan G Ramsay, Matthew Trotter, Anita K Gandhi, Rajesh Chopra, Anjan Thakurta
Lenalidomide is an immunomodulatory agent that has demonstrated clinical benefit for patients with relapsed or refractory mantle cell lymphoma (MCL); however, despite this observed clinical activity, the mechanism of action (MOA) of lenalidomide has not been characterized in this setting. We investigated the MOA of lenalidomide in clinical samples from patients enrolled in the CC-5013-MCL-002 trial (NCT00875667) comparing single-agent lenalidomide versus investigator's choice single-agent therapy and validated our findings in pre-clinical models of MCL...
August 2, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28766976/phedra-using-real-world-data-to-analyze-treatment-patterns-and-ibrutinib-effectiveness-in-hematological-malignancies
#14
Jamie Garside, Nollaig Healy, Hervé Besson, Ruben Hermans, Finlay MacDougall, Damien Lestelle, Joris Diels, Wafae Iraqi
AIM: PHEDRA (Platform for Haematology in EMEA: Data for Real World Analysis) is a unique, noninterventional project based on secondary data collection from real-world (RW) patient-level (health record) databases to understand treatment patterns in hematological malignancies. It compares ibrutinib's effectiveness with alternative treatments using RW data (RWD) and randomized clinical trials data. MATERIALS & METHODS: RWD are cleaned, validated, harmonized into a Common Data Model, and analyzed statistically alongside randomized clinical trial data...
August 2, 2017: Journal of Comparative Effectiveness Research
https://www.readbyqxmd.com/read/28766542/-efficacy-of-a-bendamustine-and-rituximab-combination-in-first-line-therapy-for-chronic-lymphocytic-leukemia-results-of-the-ben-001-study
#15
E A Stadnik, V V Strugov, T O Andreeva, Yu V Virts, A M Rumyantsev, Yu V Mirolyubova, P A Butylin, A Yu Zaritsky
AIM: To evaluate the efficacy and safety of the BR regimen containing bendamustine in patients with chronic lymphocytic leukemia (CLL) who have not previously received specific therapy. SUBJECTS AND METHODS: The results of the Russian prospective observational multicenter study BEN-001 (2012-2015) covering 196 CLL patients from 34 centers of the Russian Federation were analyzed. The diagnosis was confirmed by the results of peripheral blood lymphocyte immunophenotyping...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28762387/haematological-cancer-after-ibrutinib-car-t-cells-induce-responses
#16
Diana Romero
No abstract text is available yet for this article.
August 1, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28762081/ibrutinib-versus-previous-standard-of-care-an-adjusted-comparison-in-patients-with-relapsed-refractory-chronic-lymphocytic-leukaemia
#17
Lotta Hansson, Anna Asklid, Joris Diels, Sandra Eketorp-Sylvan, Johanna Repits, Frans Søltoft, Ulrich Jäger, Anders Österborg
This study explored the relative efficacy of ibrutinib versus previous standard-of-care treatments in relapsed/refractory patients with chronic lymphocytic leukaemia (CLL), using multivariate regression modelling to adjust for baseline prognostic factors. Individual patient data were collected from an observational Stockholm cohort of consecutive patients (n = 144) diagnosed with CLL between 2002 and 2013 who had received at least second-line treatment. Data were compared with results of the RESONATE clinical trial...
July 31, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28762015/using-genomic-information-to-guide-ibrutinib-treatment-decisions-in-chronic-lymphocytic-leukaemia-a-cost-effectiveness-analysis
#18
James Buchanan, Sarah Wordsworth, Ruth Clifford, Pauline Robbe, Jenny C Taylor, Anna Schuh, Samantha J L Knight
BACKGROUND: Genomic tests may improve the stratification of patients to receive new therapies in several disease areas. However, the use of expensive targeted therapies can impact on the cost effectiveness of these tests. This study presents an economic evaluation of genomic testing in chronic lymphocytic leukaemia in the context of the UK National Health Service. METHODS: Cost-effectiveness and cost-utility analyses (using life-years and quality-adjusted life-years) were undertaken from a National Health Service and societal perspective...
July 31, 2017: PharmacoEconomics
https://www.readbyqxmd.com/read/28760303/analysis-of-efficacy-and-tolerability-of-bruton-tyrosine-kinase-inhibitor-ibrutinib-in-various-b-cell-malignancies-in-the-general-community-a%C3%A2-single-center-experience
#19
Naveed Ali, Faizan Malik, Syed Imran Mustafa Jafri, Mary Naglak, Mark Sundermeyer, Peter V Pickens
BACKGROUND: Ibrutinib, an irreversible inhibitor of Bruton tyrosine kinase (BTK), is a novel drug that has shown significant efficacy and survival benefit for treatment of various B-cell malignancies. The primary objective of the present study was to investigate the efficacy of ibrutinib therapy in various B-cell malignancies in the general community. The secondary objectives included studying the adverse effects, ibrutinib-induced peripheral lymphocytosis, and effect on immunoglobulin levels...
July 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28755313/targeting-b-cell-signaling-in-chronic-lymphocytic-leukemia
#20
REVIEW
Jon E Arnason, Jennifer R Brown
In recent years, a revolution in the management of chronic lymphocytic leukemia (CLL) has centered on the targeting of the B cell receptor (BCR) signaling pathway. Our improved understanding of the biology of cell signaling in CLL and the development of oral kinase inhibitors directed at the BCR pathway has led to the approval of two new agents and has the potential to radically change the treatment of CLL in both the relapsed/refractory and upfront settings. In this review, we will describe the underlying biology of the BCR signaling pathway...
September 2017: Current Oncology Reports
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