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Bendamustine myeloma

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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
#1
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/28270368/clinical-outcomes-related-to-the-use-of-bendamustine-therapy-for-multiple-myeloma-patients-relapsed-refractory-to-imids-and-proteasome-inhibitors
#2
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/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
#3
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/28076910/treatment-of-patients-with-waldenstr%C3%A3-m-macroglobulinaemia-clinical-practice-guidelines-from-the-myeloma-foundation-of-australia-medical-and-scientific-advisory-group
#4
Dipti Talaulikar, Constantine S Tam, Douglas Joshua, Joy Phoebe Ho, Jeff Szer, Hang Quach, Andrew Spencer, Simon Harrison, Peter Mollee, Andrew W Roberts, Noemi Horvath, Cindy Lee, Andrew Zannettino, Ross Brown, Bradley Augustson, Wilfrid Jaksic, John Gibson, Anna Kalff, Anna Johnston, Judith Trotman, Akash Kalro, George Grigoriadis, Chris Ward, H Miles Prince
Waldenström macroglobulinaemia (WM) is an indolent B-cell malignancy characterised by the presence of immunoglobulin M (IgM) paraprotein and bone marrow infiltration by clonal small B lymphocytes, plasmacytoid lymphocytes and plasma cells. The symptoms of WM are protean, often follow an asymptomatic phase and may include complications related to the paraneoplastic effects of IgM paraprotein. The revised 2016 World Health Organization classification includes the MYD88 L265P mutation, which is seen in >90% of cases, within the diagnostic criteria for WM...
January 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28002971/new-and-developing-therapies-for-al-amyloidosis
#5
REVIEW
Giulia Zumbo, Omid Sadeghi-Alavijeh, Philip N Hawkins, Marianna Fontana
Systemic light-chain (AL) amyloidosis is an infiltrative disorder associated with an underlying plasma cells dyscrasia, in which monoclonal immunoglobulin light chains accumulate in an abnormal misfolded form as amyloid fibrils in the extracellular space. Symptoms and prognosis are governed by which organs are affected, and cardiac involvement is the major determinant of survival. Diagnosis requires demonstration of amyloid deposition and confirmation of the fibril protein type. Areas covered: This review will focus on the available treatments for systemic AL amyloidosis and on new drug targets and therapeutic approaches...
February 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/27983764/bendamustine-lenalidomide-and-dexamethasone-brd-has-high-activity-as-2-nd-line-therapy-for-relapsed-and-refractory-multiple-myeloma-a-phase-ii-trial
#6
Ulrich J M Mey, Wolfram Brugger, Heike Schwarb, Stefanie Pederiva, Andreas Schwarzer, Tobias Dechow, Paul Jehner, Jacqueline Rauh, Christian J Taverna, Mathias Schmid, Martin Schmidt-Hieber, Steffen Doerfel, Natalie Fischer, Axel Ruefer, Carsten Ziske, Wolfgang Knauf, Richard Cathomas, Roger von Moos, Felicitas Hitz, Rafael Sauter, Elke Hiendlmeyer, Nathan Cantoni, Mario Bargetzi, Christoph Driessen
The combination of lenalidomide (Revlimid(®) , R) and dexamethasone (d) is a standard regimen for patients with relapsed/refractory multiple myeloma (rrMM). With this regimen, only a small fraction of patients will achieve high quality responses [≥ very good partial response (VGPR)]. The combination of bendamustine (B), lenalidomide and dexamethasone (BRd) has shown high efficacy in patients with advanced rrMM. However, dose-limiting haematotoxicity restricted its use in extensively pre-treated patient populations...
March 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/27867671/retreatment-with-bendamustine-bortezomib-dexamethasone-in-a-patient-with-relapsed-refractory-multiple-myeloma
#7
Claudio Cerchione, Davide Nappi, Maria Di Perna, Irene Zacheo, Anna Emanuele Pareto, Marco Picardi, Lucio Catalano, Fabrizio Pane
The clinical management of relapsed/refractory multiple myeloma and the correct choice of the most suitable therapy in heavily pretreated and fragile patients are tough clinical issues for clinicians. In advanced phases of disease, the choice of available therapies becomes very poor, and the retreatment with previously adopted and effective therapy, although unpredictable, could be an effective option. In this report, we describe the clinical history of a patient, previously treated with 9 lines of therapy, refractory to bortezomib and IMIDs, for whom the retreatment with bendamustine resulted in a stable disease with good quality of life...
2016: Case Reports in Hematology
https://www.readbyqxmd.com/read/27722131/bendamustine-in-heavily-pre-treated-multiple-myeloma-patients-results-of-a-retrospective-analysis-from-the-korean-multiple-myeloma-working-party
#8
Seok Jin Kim, Soo-Mee Bang, Yoon Seok Choi, Deog-Yeon Jo, Jin Seok Kim, Hyewon Lee, Hyeon Seok Eom, Dok Hyun Yoon, Cheolwon Suh, Je-Jung Lee, Junshik Hong, Jae Hoon Lee, Youngil Koh, Kihyun Kim, Sung-Soo Yoon, Chang-Ki Min
BACKGROUND: Bendamustine may be a potential treatment option for patients with myeloma, but little is known about the utility of bendamustine as a salvage treatment, especially in Asian patients. METHODS: We performed a multicenter retrospective study of patients with relapsed or refractory myeloma who received bendamustine and prednisone. RESULTS: The records of 65 heavily pre-treated patients, who had undergone bortezomib and lenalidomide treatment (median number of previous treatments: 5), were analyzed...
September 2016: Blood Research
https://www.readbyqxmd.com/read/27525143/a-case-of-undiagnosed-hiv-infection-in-a-57-year-old-woman-with-multiple-myeloma-consequences-on-chemotherapy-efficiency-and-safety
#9
I Poizot-Martin, S Brégigeon, C Tamalet, R Bouabdallah, O Zaegel-Faucher, V Obry-Roguet, A Ivanova, C E Cano, C Solas
Background. Non-AIDS-defining cancers represent a rising health issue among HIV-infected patients. Nevertheless, HIV testing is not systematic during the initial cancer staging. Here, we report a case of HIV infection diagnosed three years after chemotherapy initiation for multiple myeloma. Results. A 57-year-old woman diagnosed with multiple myeloma underwent a first round of chemotherapy by bortezomib/lenalidomide and then with bortezomib/liposomal-doxorubicine/dexamethasone, with partial remission, poor hematological tolerance, and multiple episodes of pneumococcal infection...
2016: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/27442600/bendamustine-low-dose-dexamethasone-and-lenalidomide-bdl-for-the-treatment-of-patients-with-relapsed-refractory-multiple-myeloma-confirms-very-promising-results-in-a-phase-i-ii-study
#10
Samantha Pozzi, Massimo Gentile, Stefano Sacchi, Raffaella Marcheselli, Alessandro Corso, Federica Cocito, Pellegrino Musto, Attilio Guarini, Carla Minoia, Iolanda Vincelli, Roberto Ria, Elena Rivolti, Giuseppe Mele, Alessia Bari, Carla Mazzone, Stefania Badiali, Luigi Marcheselli, Antonio Palumbo, Fortunato Morabito
Lenalidomide and dexamethasone are an effective treatment for naïve and relapsed multiple myeloma (MM) patients. Bendamustine is a good option for B-cell malignancies showing only partial cross resistance with alkylating agents used in MM patients. Based on these considerations, we proposed a phase I/II study testing escalating doses of bendamustine and lenalidomide and fixed low doses of dexamethasone (BdL). Fifteen patients were enrolled in phase I study. Maximum tolerated dose was established at dose "level 0": bendamustine 40 mg/m(2) days 1,2; lenalidomide 10 mg days 1-21; d 40 mg days 1,8,15,22 every 28-day cycle, for six cycles...
July 21, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27363832/novel-agents-in-the-treatment-of-multiple-myeloma-a-review-about-the-future
#11
REVIEW
Leonard Naymagon, Maher Abdul-Hay
Multiple myeloma (MM) is a disease that affects plasma cells and can lead to devastating clinical features such as anemia, lytic bone lesions, hypercalcemia, and renal disease. An enhanced understanding of MM disease mechanisms has led to new more targeted treatments. There is now a plethora of treatments available for MM. In this review article, our aim is to discuss many of the novel agents that are being studied or have recently been approved for the treatment of MM. These agents include the following: immunomodulators (pomalidomide), proteasome inhibitors (carfilzomib, marizomib, ixazomib, oprozomib), alkylating agents (bendamustine), AKT inhibitors (afuresertib), BTK inhibitors (ibrutinib), CDK inhibitors (dinaciclib), histone deacetylase inhibitors (panobinostat, rocilinostat, vorinostat), IL-6 inhibitors (siltuximab), kinesin spindle protein inhibitors (filanesib), monoclonal antibodies (daratumumab, elotuzumab, indatuximab, SAR650984), and phosphoinositide 3-kinase (PI3K) inhibitors...
June 30, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27214069/bendamustine-etoposide-and-dexamethasone-to-mobilize-peripheral-blood-hematopoietic-stem-cells-for-autologous-transplantation-in-patients-with-multiple-myeloma
#12
D J Green, W I Bensinger, L A Holmberg, T Gooley, B G Till, L E Budde, J M Pagel, S L Frayo, J E Roden, L Hedin, O W Press, A K Gopal
Chemotherapeutic agents without cross-resistance to prior therapies may enhance PBSC collection and improve patient outcomes by exacting a more potent direct antitumor effect before autologous stem cell transplant. Bendamustine has broad clinical activity in transplantable lymphoid malignancies, but concern remains over the potential adverse impact of this combined alkylator-nucleoside analog on stem cell mobilization. We performed a prospective, nonrandomized phase II study including 34 patients with multiple myeloma (MM) (n=34; International Staging System (ISS) stages I (35%), II (29%) and III (24%); not scored (13%)) to evaluate bendamustine's efficacy and safety as a stem cell mobilizing agent...
October 2016: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/27088375/a-phase-ii-single-arm-prospective-study-of-bendamustine-plus-melphalan-conditioning-for-second-autologous-stem-cell-transplantation-in-de-novo-multiple-myeloma-patients-through-a-tandem-transplant-strategy
#13
M Martino, G Tripepi, G Messina, I D Vincelli, G Console, A G Recchia, M Gentile, S Molica, F Morabito
This phase II trial evaluates, for the first time, the safety and efficacy of bendamustine plus high-dose melphalan (HDM) as a conditioning regimen before the second autologous stem cell transplantation (ASCT) in previously untreated multiple myeloma (MM) patients. In total, 32 ASCT patients received HDM (200 mg/m(2)) as conditioning for the first ASCT. After 3-6 months from the first ASCT, responding patients underwent a second ASCT following bendamustine (200 mg/m(2)) and HDM (140 mg/m(2)). High-dose chemotherapy and ASCT were performed with complete neutrophil and platelet recovery in all patients...
September 2016: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/26901249/a-single-center-retrospective-analysis-of-first-line-therapy-of-multiple-myeloma-with-bendamustine-bortezomib-dexamethasone
#14
Hannes Zwickl, Elisabeth Zwickl-Traxler, Martin Pecherstorfer
The aim of this retrospective study was to evaluate the efficacy and toxicity profile of bendamustine, bortezomib, and dexamethasone (BBD) combination treatment of patients with newly diagnosed multiple myeloma (MM). BBD treatment had a response rate of 80% regarding patients with ≥ partial response (PR). Median time to best response was 87.5 days and PFS was 22 months. Median of OS was not reached. PFS of non-responding patients was significantly shortened compared to those with ≥ PR. No statistically significant differences were determined concerning age (≥ vs...
September 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/26626207/efficacy-and-safety-of-lenalidomide-treatment-in-multiple-myeloma-mm-patients-report-of-the-polish-myeloma-group
#15
MULTICENTER STUDY
L Usnarska-Zubkiewicz, J Dębski, A Butrym, W Legieć, M Hus, A Dmoszyńska, B Stella-Hołowiecka, J M Zaucha, J Januszczyk, M Rymko, T Torosian, G Charliński, E Lech-Marańda, A Malenda, A Jurczyszyn, H Urbańska-Ryś, A Druzd-Sitek, D Błońska, A Urbanowicz, J Hołojda, J Pogrzeba, P Rzepecki, J Hałka, E Subocz, R Becht, B Zdziarska, D Dytfeld, A Nowicki, Ł Bołkun, J Kłoczko, W Knopińska-Posłuszny, A Zubkiewicz-Kucharska, K Kuliczkowski
UNLABELLED: The aim of the multi-centre retrospective study was to evaluate the efficacy and safety of lenalidomide (LEN) therapy in patients with resistant or relapsed multiple myeloma (MM) as well as in patients with stable disease (LEN used due to neurological complications). The primary endpoint of this study was an overall response rate (ORR). The secondary endpoints were as follows: time to progression (TTP), overall survival (OS) and the safety of drug use. Data were collected in 19 centres of the Polish Multiple Myeloma Study Group...
January 2016: Leukemia Research
https://www.readbyqxmd.com/read/26592922/optimal-use-of-bendamustine-in-hematologic-disorders-treatment-recommendations-from-an-international-consensus-panel-an-update
#16
REVIEW
Bruce D Cheson, Wolfram Brugger, Gandhi Damaj, Martin Dreyling, Brad Kahl, Eva Kimby, Michinori Ogura, Eckhart Weidmann, Clemens-Martin Wendtner, Pier Luigi Zinzani
Bendamustine has achieved widespread international regulatory approval and is a standard agent for the treatment for chronic lymphocytic leukemia (CLL), indolent non-Hodgkin lymphoma and multiple myeloma. Since approval, the number of indications for bendamustine has expanded to include aggressive non-Hodgkin lymphoma and Hodgkin lymphoma and novel targeted therapies, based on new bendamustine regimens/combinations, are being developed against CLL and lymphomas. In 2010, an international panel of bendamustine experts met and published a set of recommendations on the safe and effective use of bendamustine in patients suffering from hematologic disorders...
2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/26581069/new-patterns-of-relapse-in-multiple-myeloma-a-case-of-light-chain-escape-in-which-flc-predicted-relapse-earlier-than-urine-and-serum-immunofixation
#17
Anna Caldini, Chiara Nozzoli, Alessandro Terreni, Michela Staderini, Margherita Berardi, Tiziana Biagioli, Marco Brogi, Alberto Bosi
Multiple myeloma (MM) is characterized, in about 80% of cases, by the production of monoclonal intact immunoglobulin and more than 95% of them have elevated concentrations of involved (i.e. of the same class of intact immunoglobulin) free light chain (FLC). The introduction of novel therapeutic strategies has changed the natural history of the disease, leading to new manifestations of relapse. Light chain escape (LCE) is a pattern of relapse in which the FLC increase is not accompanied by a concomitant raise of the original monoclonal component (MC)...
June 1, 2016: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/26331432/bendamustine-lenalidomide-and-dexamethasone-brd-is-highly-effective-with-durable-responses-in-relapsed-multiple-myeloma
#18
Shaji K Kumar, Amrita Krishnan, Betsy LaPlant, Kristina Laumann, Vivek Roy, Todd Zimmerman, Morie A Gertz, Francis K Buadi, Keith Stockerl Goldstein, Ann Birgin, Mark Fiala, Lupe Duarte, Michelle Maharaj, Joan Levy, Ravi Vij
Bendamustine is a multifunctional alkylating agent with single agent activity in myeloma. We designed the current phase 1/2 trial to determine the maximum tolerated doses (MTD) of bendamustine that can be safely combined with lenalidomide and dexamethasone and to assess the safety and efficacy of the combination. Patients with relapsed MM following at least 1 prior therapy, but no more than four lines of prior therapy and with measurable disease were enrolled. Bendamustine 75 mg/m(2) given on days 1 and 2, lenalidomide 25 mg given days 1-21 and dexamethasone 40 mg on days 1, 8, 15, and 22, was the recommended Phase 2 dose...
December 2015: American Journal of Hematology
https://www.readbyqxmd.com/read/26196503/esters-of-bendamustine-are-by-far-more-potent-cytotoxic-agents-than-the-parent-compound-against-human-sarcoma-and-carcinoma-cells
#19
Stefan Huber, Johannes Philip Huettner, Kristina Hacker, Günther Bernhardt, Jörg König, Armin Buschauer
The alkylating agent bendamustine is approved for the treatment of hematopoietic malignancies such as non-Hodgkin lymphoma, chronic lymphocytic leukemia and multiple myeloma. As preliminary data on recently disclosed bendamustine esters suggested increased cytotoxicity, we investigated representative derivatives in more detail. Especially basic esters, which are positively charged under physiological conditions, were in the crystal violet and the MTT assay up to approximately 100 times more effective than bendamustine, paralleled by a higher fraction of early apoptotic cancer cells and increased expression of p53...
2015: PloS One
https://www.readbyqxmd.com/read/26179864/recommendations-on-the-clinical-use-of-bendamustine-in-lymphoproliferative-syndromes-and-multiple-myeloma
#20
Francisco Javier Peñalver, Julio Delgado, Javier Loscertales, Jose Luis Sastre, Asunción Peña, María Teresa Olave, Santiago Osorio, Adolfo de la Fuente, Antonio Salar, Carlos Grande, Elena Pérez Ceballos, Guillermo Debén, Asunción Echeveste, Felipe Casado, Javier de la Rubia, Juan José Lahuerta, María Victoria Mateos
Bendamustine is an increasingly used hybrid alkylating agent that is active in lymphoid neoplasias via a novel mechanism of action. There are some pending questions about its use in clinical practice because of its developmental features. A consensus panel of several leading Spanish hematologists with broad experience in the clinical use of bendamustine has established recommendations for the management and treatment of hematological patients with bendamustine based on available clinical data and the experience of the participants...
May 2016: European Journal of Haematology
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