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Waldenstrom macroglobulinemia

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https://www.readbyqxmd.com/read/28095146/phase-i-first-in-human-study-of-venetoclax-in-patients-with-relapsed-or-refractory-non-hodgkin-lymphoma
#1
Matthew S Davids, Andrew W Roberts, John F Seymour, John M Pagel, Brad S Kahl, William G Wierda, Soham Puvvada, Thomas J Kipps, Mary Ann Anderson, Ahmed Hamed Salem, Martin Dunbar, Ming Zhu, Franklin Peale, Jeremy A Ross, Lori Gressick, Monali Desai, Su Young Kim, Maria Verdugo, Rod A Humerickhouse, Gary B Gordon, John F Gerecitano
Purpose B-cell leukemia/lymphoma-2 (BCL-2) overexpression is common in many non-Hodgkin lymphoma (NHL) subtypes. A phase I trial in patients with NHL was conducted to determine safety, pharmacokinetics, and efficacy of venetoclax, a selective, potent, orally bioavailable BCL-2 inhibitor. Patients and Methods A total of 106 patients with relapsed or refractory NHL received venetoclax once daily until progressive disease or unacceptable toxicity at target doses from 200 to 1,200 mg in dose-escalation and safety expansion cohorts...
January 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28094456/waldenstr%C3%A3-m-macroglobulinemia-2017-update-on-diagnosis-risk-stratification-and-management
#2
Morie A Gertz
: Disease Overview: Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and rarely hyperviscosity. DIAGNOSIS: Presence of IgM monoclonal protein associated with ≥10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. The L265P mutation in MYD88 is detectable in more than 90% of patients. Risk Stratification: Age, hemoglobin level, platelet count, β2 microglobulin, and monoclonal IgM concentrations are characteristics required for prognosis...
February 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28088969/-the-clinical-features-of-patients-with-lymphoplasmacytic-diseases-harboring-myd88-l265p-mutation
#3
Y Ren, B Q Zhou, Y Xu, C C Fu, H J Shen, Z X Ding, D P Wu
Objective: To explore the clinical features of lymphoplasmacytic diseases with MyD88 L265P mutation. Methods: To analyze the distribution of MYD88 L265P mutation in patients with lymphoplasmacytic diseases by using of ARMS PCR-CE. Results: There were 25(30.9%) MyD88 L265P mutated patients in 81 patients. The mutation was frequently observed in 14 patients with WM (77.8%, 14/18), 2 patients with lymphoplasmacytic lymphoma (66.7%, 2/3), 1 acute lymphocytic leukemia patient (50.0%, 1/2), 3 multiple myeloma patients (30...
December 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28056114/diagnosis-and-management-of-waldenstr%C3%A3-m-macroglobulinemia-mayo-stratification-of-macroglobulinemia-and-risk-adapted-therapy-msmart-guidelines-2016
#4
Prashant Kapoor, Stephen M Ansell, Rafael Fonseca, Asher Chanan-Khan, Robert A Kyle, Shaji K Kumar, Joseph R Mikhael, Thomas E Witzig, Michelle Mauermann, Angela Dispenzieri, Sikander Ailawadhi, A Keith Stewart, Martha Q Lacy, Carrie A Thompson, Francis K Buadi, David Dingli, William G Morice, Ronald S Go, Dragan Jevremovic, Taimur Sher, Rebecca L King, Esteban Braggio, Ann Novak, Vivek Roy, Rhett P Ketterling, Patricia T Greipp, Martha Grogan, Ivana N Micallef, P Leif Bergsagel, Joseph P Colgan, Nelson Leung, Wilson I Gonsalves, Yi Lin, David J Inwards, Suzanne R Hayman, Grzegorz S Nowakowski, Patrick B Johnston, Steven J Russell, Svetomir N Markovic, Steven R Zeldenrust, Yi L Hwa, John A Lust, Luis F Porrata, Thomas M Habermann, S Vincent Rajkumar, Morie A Gertz, Craig B Reeder
Importance: Waldenström macroglobulinemia (WM), an IgM-associated lymphoplasmacytic lymphoma, has witnessed several practice-altering advances in recent years. With availability of a wider array of therapies, the management strategies have become increasingly complex. Our multidisciplinary team appraised studies published or presented up to December 2015 to provide consensus recommendations for a risk-adapted approach to WM, using a grading system. Observations: Waldenström macroglobulinemia remains a rare, incurable cancer, with a heterogeneous disease course...
January 5, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28043164/current-treatment-options-and-investigational-drugs-for-waldenstrom-s-macroglobulinemia
#5
Maria Gavriatopoulou, Evangelos Terpos, Efstathios Kastritis, Meletios A Dimopoulos
Waldenström's Macroglobulinemia (WM) is a rare, indolent, incurable, low-grade B-cell lymphoplasmacytic neoplasm. This review article provides a modern clinical perspective of the individualized management of patients with symptomatic WM, in the context of the updated treatment guidelines and the currently available trial data. Areas covered: Rituximab-based regimens (such as the dexamethasone, rituximab and cyclophosphamide combination, DRC) are the most widely used in the management of both newly diagnosed and relapsed/refractory patients with WM...
January 3, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28024494/-pet-ct-manifestation-and-clinical-analysis-of-waldenstrom-macroglobulinemia
#6
Chong-Yang Ding, Hong-Yu Liu, Zhe Guo, Tian-Nu Li
OBJECTIVE: To investigate the PET-CT manifestation and clinical features of patients with Waldenstrom macroglobulinemia(WM) . METHODS: The clinical features, laboratorial examination results and PET-CT manifestation of 12 patients with WM were analyzed retrospectively. RESULTS: The average age of 12 patients with WM was 63.5 years old, the most common incipient symptoms were fatigue and hyperviscosity syndrome. The median SUVmax of bone marrow was 4...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/27980745/a-case-of-new-onset-cardiomyopathy-and-ventricular-tachycardia-in-a-patient-receiving-ibrutinib-for-relapsed-mantle-cell-lymphoma
#7
Natalie Wallace, Ellice Wong, Dennis Cooper, Herta Chao
Ibrutinib is a first-in-class inhibitor of Bruton's tyrosine kinase, which is approved for use in chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's macroglobulinemia. Although ibrutinib has been linked to an increased incidence of atrial fibrillation, this is the first report of an association with nonischemic cardiomyopathy and ventricular arrhythmia.
December 2016: Clinical Case Reports
https://www.readbyqxmd.com/read/27974705/are-neurological-complications-of-monoclonal-gammopathy-of-undetermined-significance-underestimated
#8
Normann Steiner, Angelika Schwärzler, Georg Göbel, Wolfgang Löscher, Julia Wanschitz, Eberhard Gunsilius
OBJECTIVES: Monoclonal gammopathy of undetermined significance (MGUS) is a premalignancy preceding multiple myeloma (MM) or related disorders. Neurological symptoms caused by the monoclonal immunoglobulins or free light-chains are often associated with a high morbidity. We analyzed the prevalence of neuropathy, clinical features and the long-term outcome in 223 patients (pts.) with MGUS. PATIENTS AND METHODS: Between 1/2005 and 3/2015, 223 adult pts. with MGUS were identified in our database...
December 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27971720/cost-effectiveness-analysis-of-ibrutinib-for-waldenstr%C3%A3-m-macroglobulinemia-in-italy
#9
A Aiello, A D'Ausilio, F Randon, R Lo Muto
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27956157/ibrutinib-for-patients-with-rituximab-refractory-waldenstr%C3%A3-m-s-macroglobulinaemia-innovate-an-open-label-substudy-of-an-international-multicentre-phase-3-trial
#10
Meletios A Dimopoulos, Judith Trotman, Alessandra Tedeschi, Jeffrey V Matous, David Macdonald, Constantine Tam, Olivier Tournilhac, Shuo Ma, Albert Oriol, Leonard T Heffner, Chaim Shustik, Ramón García-Sanz, Robert F Cornell, Carlos Fernández de Larrea, Jorge J Castillo, Miquel Granell, Marie-Christine Kyrtsonis, Veronique Leblond, Argiris Symeonidis, Efstathios Kastritis, Priyanka Singh, Jianling Li, Thorsten Graef, Elizabeth Bilotti, Steven Treon, Christian Buske
BACKGROUND: In the era of widespread rituximab use for Waldenström's macroglobulinaemia, new treatment options for patients with rituximab-refractory disease are an important clinical need. Ibrutinib has induced durable responses in previously treated patients with Waldenström's macroglobulinaemia. We assessed the efficacy and safety of ibrutinib in a population with rituximab-refractory disease. METHODS: This multicentre, open-label substudy was done at 19 sites in seven countries in adults aged 18 years and older with confirmed Waldenström's macroglobulinaemia, refractory to rituximab and requiring treatment...
December 9, 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27956155/ibrutinib-in-waldenstr%C3%A3-m-s-macroglobulinemia-revamping-the-landscape
#11
Bruce D David Cheson
No abstract text is available yet for this article.
December 9, 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27899193/genetic-predisposition-to-leukemia-and-other-hematologic-malignancies
#12
REVIEW
Simone Feurstein, Michael W Drazer, Lucy A Godley
In this review, we provide an overview of familial myelodysplastic syndromes (MDS)/acute leukemia (AL) and bone marrow failure syndromes, as well as insights into familial myeloproliferative neoplasms (MPNs), familial multiple myeloma (MM), familial Waldenström macroglobulinemia (WM), familial lymphoma, and cancer predisposition syndromes with increased risk of MDS/AL. This field will continue to accelerate as next-generation sequencing (NGS) techniques identify novel predisposition alleles in families with a genetic predisposition to hematologic malignancies...
October 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/27890075/clone-specific-myd88-l265p-and-cxcr4-mutation-status-can-provide-clinical-utility-in-suspected-waldenstr%C3%A3-m-macroglobulinemia-lymphoplasmacytic-lymphoma
#13
Bettina Burnworth, Zhixing Wang, Timothy P Singleton, Angela Bennington, Wayne Fritschle, Richard Bennington, Lisa Eidenschink Brodersen, Denise A Wells, Michael R Loken, Barbara K Zehentner
MYD88 L265P, a diagnostic marker for lymphoplasmacytic lymphoma (LPL)/Waldenström macroglobulinemia (WM) can also be detected in other hematopoietic malignancies. We demonstrate a novel approach to increase the specificity of this marker for WM/LPL diagnosis by combining flow cytometric cell sorting with molecular analysis. Clonal B-lymphocyte and co-occurring clonal plasma cell populations of low-grade B-cell lymphomas were sorted by flow cytometry and analyzed for immunoglobulin gene rearrangements (PCR), and for MYD88 and CXCR4 mutations...
December 2016: Leukemia Research
https://www.readbyqxmd.com/read/27872060/bdr-in-newly-diagnosed-patients-with-wm-final-analysis-of-a-phase-2-study-after-a-minimum-follow-up-of-6-years
#14
Maria Gavriatopoulou, Ramón García-Sanz, Efstathios Kastritis, Pierre Morel, Marie-Christine Kyrtsonis, Eurydiki Michalis, Zafiris Kartasis, Xavier Leleu, Giovanni Palladini, Alessandra Tedeschi, Dimitra Gika, Giampaolo Merlini, Pieter Sonneveld, Meletios A Dimopoulos
In this phase 2 multicenter trial, we evaluated the efficacy of the combination of bortezomib, dexamethasone and rituximab (BDR) in 59 previously untreated symptomatic patients with Waldenström's Macroglobulinemia, most of which were of advanced age and with adverse prognostic factors. BDR consisted of a single 21-day cycle of bortezomib alone (1.3 mg/m(2) IV days 1, 4, 8, and 11), followed by weekly IV bortezomib (1.6 mg/m(2) days 1, 8, 15, and 22) for 4 additional 35-day cycles, with IV dexamethasone (40 mg) and IV rituximab (375 mg/m(2)) on cycles 2 and 5, for a total treatment duration of 23 weeks...
November 21, 2016: Blood
https://www.readbyqxmd.com/read/27836860/prospective-multicenter-clinical-trial-of-everolimus-as-primary-therapy-in-waldenstrom-macroglobulinemia-wmctg-09-214
#15
Steven P Treon, Kirsten Meid, Christina Tripsas, Leonard T Heffner, Herbert Eradat, Ashraf Z Badros, Lian Xu, Zachary R Hunter, Guang Yang, Christopher J Petterson, Joshua Gustine, Jorge J Castillo, Jeffrey Matous, Irene M Ghobrial
PURPOSE: Everolimus inhibits mTOR, a component of PI3K/AKT pro-survival signaling triggered by MYD88 and CXCR4 activating mutations in Waldenstrom's Macroglobulinemia (WM). EXPERIMENTAL DESIGN: We evaluated everolimus in a prospective, multicenter study of 33 symptomatic, previously untreated WM patients. Intended therapy consisted of everolimus (10 mg/day) until progression or unacceptable toxicity. Dose de-escalation was permitted. The study was registered at www...
November 11, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27825469/the-role-of-stem-cell-transplantation-in-waldenstrom-s-macroglobulinemia
#16
REVIEW
Rajshekhar Chakraborty, Eli Muchtar, Morie A Gertz
Waldenstrom's macroglobulinemia (WM) is an indolent B-cell lymphoma, which is highly chemosensitive, with an overall response rate over 90% to novel agents. However, most patients eventually relapse after response to first-line chemotherapy, necessitating further treatment. The possibility of long-lasting remission after high-dose cytotoxic chemotherapy followed by stem cell rescue is high in WM due to the chemosensitive nature of the disease and lower proliferative activity compared to multiple myeloma. In this paper, we have reviewed current evidence on autologous (auto-) and allogeneic (allo-) stem cell transplantation (SCT) in WM...
June 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27825468/novel-therapeutic-targets-in-waldenstrom-macroglobulinemia
#17
REVIEW
Aneel Paulus, Sikander Ailawadhi, Asher Chanan-Khan
Understanding of molecular mechanisms that drive Waldenstrom macroglobulinemia (WM) cell survival are rapidly evolving. This review briefly highlights emerging "WM-relevant" targets; for which therapeutic strategies are currently being investigated in preclinical and clinical studies. With the discovery of MYD88L265P signaling and remarkable activity of ibrutinib in WM, other targets within the B-cell receptor pathway are now being focused on for therapeutic intervention. Additional targets which play a role in WM cell survival include TLR7, 8 and 9, proteasome-associated deubiquitinating enzymes (USP14 and UCHL5), XPO1/CRM1 and AURKA...
June 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27825467/future-therapeutic-options-for-patients-with-waldenstr%C3%A3-m-macroglobulinemia
#18
REVIEW
Jorge J Castillo, Zachary R Hunter, Guang Yang, Kimon Argyropoulos, M Lia Palomba, Steven P Treon
Waldenström macroglobulinemia (WM) is a rare lymphoma characterized by the accumulation of IgM-producing lymphoplasmacytic cells. Although WM patients can experience prolonged remissions, the disease invariably recurs. Therefore, novel treatments associated with higher success rates and lower toxicity profiles are needed. The discovery of recurrent mutations in the MYD88 and CXCR4 genes has unraveled potential therapeutic targets in WM patients. As a result of these findings and based on the design and execution of a prospective clinical trial, the FDA granted approval to ibrutinib, an oral Bruton tyrosine kinase (BTK) inhibitor, to treat patients with symptomatic WM...
June 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27825465/monoclonal-gammopathy-of-undetermined-significance-and-waldenstr%C3%A3-m-s-macroglobulinemia
#19
REVIEW
Sham Mailankody, Ola Landgren
Since the initial identification of patients with monoclonal elevation of gamma globulin and associated clinical symptoms in 1944 by Jan Waldenström, several new insights have been gained using a range of approaches. For example, IgM monoclonal gammopathy of undetermined significance and smoldering Waldenström's macroglobulinemia are defined clinical precursor states to symptomatic Waldenström's macroglobulinemia. Epidemiologic studies have established the prevalence of these conditions and the estimated risk of progression to symptomatic disease...
June 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27825464/prognostic-factors-and-indications-for-treatment-of-waldenstr%C3%A3-m-s-macroglobulinemia
#20
REVIEW
Robert A Kyle, Stephen M Ansell, Prashant Kapoor
Waldenström's Macroglobulinemia (WM) is characterized by the presence of an IgM monoclonal protein regardless of its size, 10% or more bone marrow infiltration by small lymphocytes with a plasmacytoid or plasma cell differentiation. These cells usually have the following markers: IgM+, CD5(-), CD10(-), CD19(+), CD20(+) and CD23(-). Chronic lymphocytic leukemia as well as other lymphoproliferative disorders such as mantle cell, marginal zone and mucosa-associated lymphoid tissue (MALT) lymphoma must be excluded...
June 2016: Best Practice & Research. Clinical Haematology
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