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https://www.readbyqxmd.com/read/28324270/obinutuzumab-a-review-in-rituximab-refractory-or-relapsed-follicular-lymphoma
#1
REVIEW
Sohita Dhillon
Obinutuzumab (Gazyva(®), Gazyvaro(®)) is a recombinant, monoclonal, humanized and glycoengineered, type II, anti-CD20, IgG1 antibody. It has recently been granted an additional indication for the treatment of patients with follicular lymphoma who relapsed after, or are refractory to, a rituximab-containing regimen. In the primary analysis of the large, phase III GADOLIN study, induction therapy with obinutuzumab plus bendamustine followed by obinutuzumab maintenance prolonged progression-free survival (PFS) to a statistically significant extent relative to induction with bendamustine monotherapy in patients with indolent non-Hodgkin's lymphoma (iNHL)...
March 21, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28315173/ricolinostat-a-selective-hdac6-inhibitor-shows-anti-lymphoma-cell-activity-alone-and-in-combination-with-bendamustine
#2
Maria Cosenza, Monica Civallero, Luigi Marcheselli, Stefano Sacchi, Samantha Pozzi
Histone deacetylase inhibitors (HDACis) have emerged as a new class of anticancer agents, targeting the biological process including cell cycle and apoptosis. We investigated and explained the anticancer effects of an HDAC6 inhibitor, ricolinostat alone and in combination with bendamustine in lymphoma cell lines. Cell viability was measured by MTT assay. Apoptosis, reactive oxygen species (ROS) generation, Bcl-2 protein expression, cell cycle progression and tubuline expression were determined by flow cytometry...
March 17, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28314788/the-parp-inhibitor-veliparib-can-be-safely-added-to-bendamustine-and-rituximab-and-has-preliminary-evidence-of-activity-in-b-cell-lymphoma
#3
Jacob D Soumerai, Andrew D Zelenetz, Craig Moskowitz, M Lia Palomba, Paul A Hamlin, Ariela Noy, David J Straus, Alison J Moskowitz, Anas Younes, Matthew J Matasar, Steven Horwitz, Carol Portlock, Jason Konner, Mrinal M Gounder, David M Hyman, Martin H Voss, Matthew G Fury, Devika Gajria, Richard D Carvajal, Alan L Ho, Jan H Beumer, Brian Kiesel, Zhigang Zhang, Alice Chen, Richard F Little, Christine Jarjies, Thu O Dang, Fallon France, Nishant Mishra, John F Gerecitano
PURPOSE: The PARP inhibitor veliparib enhances the cytotoxicity of alkylating agents. This phase 1 study evaluated veliparib with the bifunctional alkylator bendamustine (VB) in patients with relapsed/refractory lymphoma, multiple myeloma, and solid malignancies, with a cohort expansion of VB with rituximab (VBR) in patients with B-cell lymphomas. EXPERIMENTAL DESIGN: This dose-escalation study evaluated safety, pharmacokinetics and preliminary efficacy of veliparib (20-400 mg BID, days 1-7 of 28-day cycle) and bendamustine (70 and 90 mg/m2 IV, days 1 and 2)...
March 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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
#4
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/28286923/maintenance-therapies-in-indolent-lymphomas-should-recent-data-change-the-standard-of-care
#5
REVIEW
Michael T Tees, Ian W Flinn
The overall benefit of maintenance therapy for patients with an indolent lymphoma continues to go unanswered. A myriad of variables contribute to the lack of clear clinical guidance. First, the disease course is slow and treatment may not be required for years, requiring a long follow-up to prospectively study. Second, due to the long lag time from study initiation to conclusion, many of the induction therapies used at the onset of the study may not be favored at present, providing a conclusion that cannot be reconciled with current clinical practice...
March 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28276536/obinutuzumab-in-follicular-lymphoma
#6
N Martinez-Calle, R Figueroa-Mora, S Villar-Fernandez, M Marcos-Jubilar, C Panizo
The CD20 marker continues to be exploited as a therapeutic target for non-Hodgkin's lymphoma. Obinutuzumab is part of a new generation of anti-CD20 monoclonal antibodies, which are synthesized using molecular engineering technology, resulting in novel target epitopes and unprecedented optimization of antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. Rituximab is the current gold standard for anti-CD20 therapy, yet despite outstanding results published over the past decade, many patients continue to relapse after anti-CD20 regimens...
December 2016: Drugs of Today
https://www.readbyqxmd.com/read/28273193/-drug-therapy-of-lymphomas
#7
Lajos Gergely
The therapy of lymphomas has undergone a major expansion during the last decade. Novel therapeutic targets have appeared beyond classical chemotherapeutic combinations. These novel drugs have very pronounced action across lymphoma types, and their toxicity profile is usually better tolerable compared to standard chemotherapies. These new therapies are enabling us to offer treatment to those patients who have refractory disease, and we had no option to treat them before these drugs. The author describes several new therapeutic options...
March 8, 2017: Magyar Onkologia
https://www.readbyqxmd.com/read/28271952/relapsed-chronic-lymphocytic-leukemia-retreated-with-rituximab-interim-results-of-the-perle-study
#8
Driss Chaoui, Sylvain Choquet, Laurence Sanhes, Béatrice Mahé, Maya Hacini, Olivier Fitoussi, Yazid Arkam, Hubert Orfeuvre, Marie-Sarah Dilhuydy, Marly Barry, Eric Jourdan, Brigitte Dreyfus, Adrian Tempescul, Stéphane Leprêtre, Aurélie Bardet, Pierre Leconte, Marc Maynadié, Alain Delmer
This prospective non-interventional study assessed the management of relapsed/refractory CLL after one or two treatments with rituximab, and retreatment with a rituximab-based regimen. An interim analysis was performed at the end of the induction period in 192 evaluable patients. Median age was 72 years [35-89], first relapse (55%), and second relapse (45%). Rituximab administered during first (68%), second (92%), or both treatment lines (20%). R-bendamustine administered in 56% of patients, R-purine analogs (21%), and R-alkylating agents (19%)...
June 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28270368/clinical-outcomes-related-to-the-use-of-bendamustine-therapy-for-multiple-myeloma-patients-relapsed-refractory-to-imids-and-proteasome-inhibitors
#9
Fevzi Fırat Yalnız, Nihan Akkoç, Ayşe Salihoğlu, M Cem Ar, Seniz Aydın, A Emre Eşkazan, Teoman Soysal, Yıldız Aydın
Multiple myeloma (MM) patients who are relapsed or refractory to both proteasome inhibitory (PIs) and immunomodulatory drugs (IMiDs) have been reported to have poor outcome. Bendamustine has been reported to have an antitumor effect in newly diagnosed as well as relapsed refractory multiple myeloma (RRMM). The aim of this retrospective study was to evaluate the efficacy of bendamustine therapy in heavily pretreated MM patients, who were refractory to PIs and IMiDs. Nineteen RRMM patients treated either with bendamustine and steroid (n=13) or a combination of bendamustine in with novel drugs (n=6) were included...
March 8, 2017: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/28243993/what-is-optimal-front-line-therapy-for-chronic-lymphocytic-leukemia-in-2017
#10
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/28204914/salvage-therapy-with-bendamustine-for-temozolomide-refractory-recurrent-anaplastic-gliomas-a-prospective-phase-ii-trial
#11
Marc C Chamberlain, Howard Colman, Bryan T Kim, Jeffrey Raizer
There is no standard therapy for recurrent anaplastic glioma (AG). Salvage therapies include alkylator-based chemotherapy, re-resection with or without carmustine implants, re-irradiation and bevacizumab. Bendamustine is a novel bifunctional alkylator with CNS penetration never previously evaluated in AG. Assess response and toxicity of bendamustine in recurrent AG in a phase II trial. Adults with radiation and temozolomide refractory recurrent AG were treated with bendamustine. A cycle of bendamustine was defined as two consecutive days of treatment (100 mg/m(2)/day) administered once every 4 weeks...
February 16, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28194058/l-probe-a-novel-non-anthracycline-combination-chemotherapy-regimen-for-aggressive-b-cell-non-hodgkin-lymphoma-in-elderly-patients
#12
Arjun Datt Law, Gaurav Prakash, Alka Khadwal, Ashim Das, Subhash Varma, Pankaj Malhotra
The management of aggressive B cell lymphomas in elderly patients is associated with poor tolerability of commonly used chemotherapeutic agents. The safety and tolerability of a novel combination chemotherapy regimen utilizing rituximab, lenalidomide, bendamustine, vincristine and prednisolone was assessed in a series of elderly patients with new onset or relapsed/refractory aggressive B cell lymphoma and inability to receive conventional chemotherapy due to poor performance status and/or significant comorbidities...
March 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/28190866/splenic-marginal-zone-lymphoma-uncovered-after-a-10-year-follow-up-as-anemia-of-unknown-cause
#13
Asumi Koyama, Chieko Shiotani, Toshio Kurihara, Toshiki Mushino, Yukiharu Okamoto, Tatsunori Tamaki, Takashi Ozaki, Kouichi Ohshima, Shinobu Tamura
A 75-year-old man was referred to our hospital for evaluation of persistent anemia. Despite repeated diagnostic tests, including bone marrow aspiration, the cause of his anemia remained unknown. On each occasion, computed tomography had revealed neither swollen lymph nodes nor splenomegaly. After a 10-year follow-up period, he was admitted with general fatigue and had developed splenomegaly as well as the anemia. Bone marrow biopsy revealed increased abnormal lymphocytes with short villi that were positive for CD11c, CD19, CD20, and kappa chain, but not for CD5, CD10, CD23, or cyclin D1, according to flow cytometry...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28187444/idelalisib-and-bendamustine-combination-is-synergistic-and-increases-dna-damage-response-in-chronic-lymphocytic-leukemia-cells
#14
Prexy Modi, Kumudha Balakrishnan, Qingshan Yang, William G Wierda, Michael J Keating, Varsha Gandhi
Idelalisib is a targeted agent that potently inhibits PI3Kδ which is exclusively expressed in hematological cells. Bendamustine is a well-tolerated cytotoxic alkylating agent which has been extensively used for treatment of chronic lymphocytic leukemia (CLL). Both these agents are FDA-approved for CLL. To increase the potency of idelalisib and bendamustine, we tested their combination in primary CLL lymphocytes. While each compound alone produced a moderate response, combination at several concentrations resulted in synergistic cytotoxicity...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28169430/phase-ii-study-of-bendamustine-bortezomib-and-dexamethasone-bbd-in-the-first-line-treatment-of-patients-with-multiple-myeloma-who-are-not-candidates-for-high-dose-chemotherapy
#15
Jesus G Berdeja, Todd Bauer, Edward Arrowsmith, James Essell, Patrick Murphy, James A Reeves, Ralph V Boccia, William Donnellan, Ian Flinn
The combination of bendamustine, bortezomib and dexamethasone (BBD) was evaluated as a first-line therapy for multiple myeloma. The original treatment regimen of bendamustine 80 mg/m(2) , days 1, 4; bortezomib 1·3 mg/m(2) , days 1, 4, 8, 11; dexamethasone 40 mg, days 1, 2, 3, 4 on a 28-day cycle (up to 8 cycles) was efficacious but determined relatively toxic in an interim analysis. The regimen was amended to bendamustine 80 mg/m(2) , days 1, 2; bortezomib 1·3 mg/m(2) , days 1, 8, 15; dexamethasone 20 mg, days 1, 2, 8, 9, 15, 16 every 28 days (up to 8 cycles), then maintenance 1·3 mg/m(2) IV bortezomib every 2 weeks...
February 7, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28160213/a-multicenter-single-arm-phase-ii-clinical-trial-of-bendamustine-monotherapy-in-patients-with-chronic-lymphocytic-leukemia-in-japan
#16
Yoshiaki Ogawa, Koji Izutsu, Toru Kiguchi, Ilseung Choi, Yoshifusa Takatsuka, Kiyoshi Ando, Junji Suzumiya
The present study was intended to examine the efficacy and safety of bendamustine monotherapy in patients with previously untreated chronic lymphocytic leukemia (CLL) for whom treatment with fludarabine (FLU) was not suitable, and in FLU-naïve patients with relapsed/refractory CLL. We intravenously administered bendamustine 100 mg/m(2)/day on days 1 and 2 of each 28-day cycle to 10 patients (eight previously untreated; two relapsed/refractory) up to six cycles. The primary endpoint was overall response rate (ORR: partial remission or better) according to the 2008 International Workshop on the CLL guidelines...
February 3, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28152957/real-world-treatment-patterns-and-health-care-resource-utilization-hru-among-patients-with-chronic-lymphocytic-leukemia-cll-by-regimen
#17
Lorie Ellis, Stephanie Korrer, Stacey DaCosta Byfield
15 Background: Few studies examine HRU of CLL, the most common hematologic malignancy in adults. This study describes HRU by the most common regimens among CLL patients (pts). METHODS: A retrospective study using a large, national U.S. claims database from 1/2007-10/2013 was conducted. Adult CLL pts (≥2 claims for CLL) with ≥1 claim for systemic anticancer therapy (SACT) were identified; first SACT claim date was the index date. Pts had to have a CLL diagnosis ≤3 months (m) prior to the index date and be continuously enrolled (CE) in the health plan for 24m pre- and ≥6m post-index date...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28152955/real-world-treatment-patterns-health-care-resource-utilization-hru-and-costs-among-patients-with-waldenstrom-macroglobulinemia-wm-initiating-therapy
#18
Lorie Ellis, Stephanie Korrer, Stacey DaCosta Byfield
17 Background: WM is a rare, indolent B-cell lymphoma with 1000 to 1500 new cases diagnosed annually in the US. The disease is incurable with current therapy. Prior to January 2015 when ibrutinib was approved by the US FDA for WM, there were no therapies approved in this indication. This study describes initial systemic anti-cancer therapy (SACT) and HRU among WM patients (pts). METHODS: A retrospective study using a large, national US claims database from 1/2007-10/2013 was conducted...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28139405/idelalisib-or-placebo-in-combination-with-bendamustine-and-rituximab-in-patients-with-relapsed-or-refractory-chronic-lymphocytic-leukaemia-interim-results-from-a-phase-3-randomised-double-blind-placebo-controlled-trial
#19
Andrew D Zelenetz, Jacqueline C Barrientos, Jennifer R Brown, Bertrand Coiffier, Julio Delgado, Miklós Egyed, Paolo Ghia, Árpád Illés, Wojciech Jurczak, Paula Marlton, Marco Montillo, Franck Morschhauser, Alexander S Pristupa, Tadeusz Robak, Jeff P Sharman, David Simpson, Lukáš Smolej, Eugen Tausch, Adeboye H Adewoye, Lyndah K Dreiling, Yeonhee Kim, Stephan Stilgenbauer, Peter Hillmen
BACKGROUND: Bendamustine plus rituximab is a standard of care for the management of patients with relapsed or refractory chronic lymphocytic leukaemia. New therapies are needed to improve clinically relevant outcomes in these patients. We assessed the efficacy and safety of adding idelalisib, a first-in-class targeted phosphoinositide-3-kinase δ inhibitor, to bendamustine plus rituximab in this population. METHODS: For this international, multicentre, double-blind, placebo-controlled trial, adult patients (≥18 years) with relapsed or refractory chronic lymphocytic leukaemia requiring treatment who had measurable lymphadenopathy by CT or MRI and disease progression within 36 months since their last previous therapy were enrolled...
January 27, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28125678/inhibition-of-stat3-by-anticancer-drug-bendamustine
#20
Kazunori Iwamoto, Yutaka Uehara, Yukie Inoue, Kyoko Taguchi, Daisuke Muraoka, Naohisa Ogo, Kenji Matsuno, Akira Asai
Bendamustine (BENDA), which bears the bis(2-chloroethyl)amino moiety, is an alkylating agent that stops the growth of cancer cells by binding to DNA and interfering with its replication. However, the mechanism of action underlying its excellent clinical efficacy remains unclear. In this work, we report that BENDA inhibits signal transducer and activator of transcription 3 (STAT3). In an AlphaScreen-based biochemical assay using recombinant human STAT3, binding of STAT3-Src homology 2 (SH2) to the phosphotyrosine (pTyr, pY) peptide was inhibited by BENDA but not by the inactive metabolite dihydroxy bendamustine (HP2)...
2017: PloS One
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