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Phase III multiple myelomA

Alejandro Losada, María José Muñoz-Alonso, Carolina García, Pedro A Sánchez-Murcia, Juan Fernando Martínez-Leal, Juan Manuel Domínguez, M Pilar Lillo, Federico Gago, Carlos M Galmarini
eEF1A2 is one of the isoforms of the alpha subunit of the eukaryotic Elongation Factor 1. It is overexpressed in human tumors and is endowed with oncogenic properties, favoring tumor cell proliferation while inhibiting apoptosis. We demonstrate that plitidepsin, an antitumor agent of marine origin that has successfully completed a phase-III clinical trial for multiple myeloma, exerts its antitumor activity by targeting eEF1A2. The drug interacts with eEF1A2 with a KD of 80 nM and a target residence time of circa 9 min...
October 7, 2016: Scientific Reports
(no author information available yet)
A phase III trial suggests that the combination of daratumumab, bortezomib, and dexamethasone is more powerful in patients with relapsed or relapsed and refractory melanoma than bortezomib plus dexamethasone. Patients who received all three drugs had a higher overall response rate and improved 12-month progression-free survival.
September 14, 2016: Cancer Discovery
Alessandra Larocca, Antonio Palumbo
The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice...
September 6, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
A Keith Stewart, Meletios A Dimopoulos, Tamás Masszi, Ivan Špička, Albert Oriol, Roman Hájek, Laura Rosiñol, David S Siegel, Ruben Niesvizky, Andrzej J Jakubowiak, Jesus F San-Miguel, Heinz Ludwig, Jacqui Buchanan, Kim Cocks, Xinqun Yang, Biao Xing, Naseem Zojwalla, Margaret Tonda, Philippe Moreau, Antonio Palumbo
PURPOSE: To determine the effects of carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd) on health-related quality of life (HR-QoL) in the Carfilzomib, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone for the Treatment of Patients With Relapsed Multiple Myeloma (ASPIRE) trial. METHODS: Patients with relapsed multiple myeloma were randomly assigned to receive KRd or Rd. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and myeloma-specific module were administered at baseline; day 1 of cycles 3, 6, 12, and 18; and after treatment...
September 6, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Noa Biran, Scott D Rowley, David H Vesole, Shijia Zhang, Michele L Donato, Joshua Richter, Alan P Skarbnik, Andrew Pecora, David S Siegel
Escalating doses of bortezomib with high-dose melphalan was evaluated as as a conditioning regimen for autologous stem cell transplantation (ASCT) in patients with relapsed or refractory multiple myeloma (MM). MM patients with less than a partial remission (PR) (or 50% reduction) compared to their pretransplantation paraprotein parameters after a prior ASCT with melphalan conditioning, or who were in relapse after a prior autologous transplantation, were eligible for study. Bortezomib was dose escalated in steps of 1, 1...
August 31, 2016: Biology of Blood and Marrow Transplantation
Hila Magen, Eli Muchtar
Elotuzumab is a monoclonal antibody directed against the SLAMF7 receptor, expressed on normal and malignant plasma cells with a lower expression on other lymphoid cells such as natural killer (NK) cells. Elotuzumab has no significant antimyeloma activity when given as a single agent to patients with relapsed or refractory multiple myeloma (RRMM). However, when combined with other antimyeloma agents, it results in improved response and outcome. Owing to the results from the landmark ELOQUENT-2 phase III clinical trial, which compared lenalidomide and dexamethasone with or without elotuzumab in patients with RRMM, elotuzumab in combination with lenalidomide and dexamethasone was approved by the American Food and Drug Administration (FDA) in November 2015 for multiple myeloma (MM) patients who received one to three prior lines of therapy...
August 2016: Therapeutic Advances in Hematology
S J Jacobus, S V Rajkumar, M Weiss, A K Stewart, E A Stadtmauer, N S Callander, L M Dreosti, M Q Lacy, R Fonseca
No abstract text is available yet for this article.
2016: Blood Cancer Journal
R Hájek, T Masszi, M T Petrucci, A Palumbo, L Rosiñol, A Nagler, K L Yong, A Oriol, J Minarik, L Pour, M A Dimopoulos, V Maisnar, D Rossi, H Kasparu, J Van Droogenbroeck, D B Yehuda, I Hardan, M Jenner, M Calbecka, M Dávid, J de la Rubia, J Drach, Z Gasztonyi, S Górnik, X Leleu, M Munder, M Offidani, N Zojer, K Rajangam, Y-L Chang, J F San-Miguel, H Ludwig
This randomized, phase III, open-label, multicenter study compared carfilzomib monotherapy against low-dose corticosteroids and optional cyclophosphamide in relapsed and refractory multiple myeloma (RRMM). Relapsed and refractory multiple myeloma patients were randomized (1:1) to receive carfilzomib (10-min intravenous infusion; 20 mg/m(2) on days 1 and 2 of cycle 1; 27 mg/m(2) thereafter) or a control regimen of low-dose corticosteroids (84 mg of dexamethasone or equivalent corticosteroid) with optional cyclophosphamide (1400 mg) for 28-day cycles...
July 15, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Esa Jantunen, Ville Varmavuo, Jaakko Valtola
INTRODUCTION: A combination of granulocyte colony-stimulating factor (G-CSF) and chemotherapy or G-CSF alone are the most common mobilization regimens for autotransplantations. Plerixafor is used for mobilization of CD34(+) cells with G-CSF in non-Hodgkin lymphoma (NHL) and myeloma (MM) patients. AREAS COVERED: The available phase II and III data on plerixafor has been reviewed. The efficacy of plerixafor in the mobilization of CD34(+) cells in predicted poor mobilizers as well as in patients who had failed a mobilization has been evaluated...
August 2016: Expert Review of Hematology
Cyrille Hulin, Andrew Belch, Chaim Shustik, Maria Teresa Petrucci, Ulrich Dührsen, Jin Lu, Kevin Song, Philippe Rodon, Brigitte Pégourié, Laurent Garderet, Hannah Hunter, Isabelle Azais, Richard Eek, Heinz Gisslinger, Margaret Macro, Shaker Dakhil, Cristina Goncalves, Richard LeBlanc, Ken Romeril, Bruno Royer, Chantal Doyen, Xavier Leleu, Fritz Offner, Nicolas Leupin, Vanessa Houck, Guang Chen, Annette Ervin-Haynes, Meletios A Dimopoulos, Thierry Facon
PURPOSE: This analysis of the FIRST trial in patients with newly diagnosed multiple myeloma (MM) ineligible for stem-cell transplantation examined updated outcomes and impact of patient age. PATIENTS AND METHODS: Patients with untreated symptomatic MM were randomly assigned at a one-to-one-to-one ratio to lenalidomide plus low-dose dexamethasone until disease progression (Rd continuous), Rd for 72 weeks (18 cycles; Rd18), or melphalan, prednisone, and thalidomide (MPT; 72 weeks), stratified by age (≤ 75 v > 75 years), disease stage (International Staging System stage I/II v III), and country...
June 20, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Ryszard Tomasiuk, Krzysztof Gawroński, Piotr Rzepecki, Michał Rabijewski, Marek Cacko
The importance of proinflamatory cytokines and acute phase proteins in pathogenesis and progression of MM is well known. However, there are any studies evaluating the role of NT-proCN in management and treatment of MM. The aim of our study was to evaluate the concentration of NT-proCNP and acute phase proteins in patients with MM before and after stem cell transplantation. We involved 40 newly diagnosed MM patients in stage III according to the Durie-Salmon classification and treated with high dose of melphalan (200mg/m2) prior to ASCT...
August 2016: Leukemia Research
Divya Vundamati, Bruce Bostrom
Isolated monosomy-7, a rare cytogenetic abnormality in patients with pediatric acute lymphoblastic leukemia (ALL), portends a worse prognosis. Despite improvements in treatment, outcomes for patients with relapsed ALL remain poor. Novel treatments adopted from the B-cell malignancy multiple myeloma may have a role in treatment of ALL. Bortezomib is one such agent currently in phase III trials for B and T ALL. This study presents a patient with B-cell ALL and monosomy-7 who relapsed off therapy. The combination of bortezomib, lenalidomide, and dexamethasone was used to attain remission before bone marrow transplant after conventional relapse therapy failed...
August 2016: Journal of Pediatric Hematology/oncology
Cyrille Touzeau, Philippe Moreau
Pomalidomide, a very potent member of the immunomodulatory drug family, is considered a standard of care for patients with relapsed and refractory myeloma, who have previously been treated with bortezomib and lenalidomide. Pomalidomide induces both direct myeloma cell death, and indirect antimyeloma response through its impact on the microenvironment (modulation of immune response, inhibition of angiogenesis, inhibition of bone resorption). Pomalidomide in combination with dexamethasone is an approved regimen in Europe and USA based on the results of a Phase III randomized trial...
September 2016: Future Oncology
Kimberly A Redic, Shannon M Hough, Erika M Price
BACKGROUND: Panobinostat is a new agent for the treatment of relapsed and refractory multiple myeloma (rrMM) as part of a combination regimen. This article presents an overview of the mechanism of action, pharmacokinetics, safety, efficacy, patient care strategies, and role of the agent in treating rrMM patients. RESULTS: Panobinostat belongs to the class of drugs known as histone deacetylase inhibitors, and has high activity against Class I, II, and IV nonhistone deacetylases and histone deacetylases...
2016: OncoTargets and Therapy
Emma D Deeks
Venetoclax (Venclexta™) is an oral selective inhibitor of the prosurvival protein BCL-2 and therefore restores the apoptotic ability of malignant cells. The drug arose from research by Abbott Laboratories (now AbbVie) during a collaboration with Genentech and is being co-developed by AbbVie and Genentech/Roche primarily for the treatment of haematological malignancies. Venetoclax is approved in the USA for use as monotherapy in patients with chronic lymphocytic leukaemia (CLL) with the 17p deletion (as detected by an approved FDA test) who have received at least one prior therapy, and is awaiting approval for similar indications in the EU and Canada...
June 2016: Drugs
Andrzej J Jakubowiak, Marco Campioni, Ágnes Benedict, Ivan Houisse, Eszter Tichy, Andromachi Giannopoulou, Sanjay K Aggarwal, Beth L Barber, Sumeet Panjabi
OBJECTIVE: To assess the economic value of carfilzomib (Kyprolis), this study developed the Kyprolis Global Economic Model (K-GEM), which examined from a United States (US) payer perspective the cost-effectiveness of carfilzomib-lenalidomide-dexamethasone (KRd) versus lenalidomide-dexamethasone (Rd) in relapsed multiple myeloma (RMM; 1-3 prior therapies) based on results from the phase III ASPIRE trial that directly compared these regimens. METHODS: A partitioned survival model that included three health states of progression-free (on or off treatment), post-progression, and death was developed...
June 16, 2016: Journal of Medical Economics
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...
May 23, 2016: Bone Marrow Transplantation
Danielle A Stegmann
Despite advances in drug therapy of the orphan disease multiple myeloma, patients relapse or become refractory to first-line therapy, and the disease remains incurable. Therefore, histone deacetylase inhibitors have emerged as a new class of anti-myeloma drugs, with synergistic results on progression free survival when given in combination to current first-line therapy. Histone deacetylase inhibitors influence gene expression of target genes. Based on results of an extensive multicenter phase III trial, panobinostat was approved by the FDA in February 2015 as the first histone deacetylase inhibitor for the treatment of multiple myeloma...
April 2016: Medizinische Monatsschrift Für Pharmazeuten
Flora Zagouri, Evangelos Terpos, Efstathios Kastritis, Meletios A Dimopoulos
INTRODUCTION: Monoclonal antibodies mark the beginning of a new era in the context of multiple myeloma (MM) treatment. Numerous antibodies have been tested or are currently in development for patients with MM, in order to improve tolerability and quality of life. AREAS COVERED: This manuscript reviews emerging antibodies for the treatment of MM i.e. elotuzumab, daratumumab, MOR03087, isatuximab, bevacizumab, cetuximab, siltuximab, tocilizumab, elsilimomab, azintrel, rituximab, tositumomab, milatuzumab, lucatumumab, dacetuzumab, figitumumab, dalotuzumab, AVE1642, tabalumab, pembrolizumab, pidilizumab, nivolumab...
June 2016: Expert Opinion on Emerging Drugs
Sarah Brown, Samantha Hinsley, Mónica Ballesteros, Sue Bourne, Paul McGarry, Debbie Sherratt, Louise Flanagan, Walter Gregory, Jamie Cavenagh, Roger Owen, Cathy Williams, Martin Kaiser, Eric Low, Kwee Yong
BACKGROUND: Multiple myeloma is a plasma cell tumour with an annual incidence in the UK of approximately 40-50 per million i.e. about 4500 new cases per annum. The triple combination cyclophosphamide, bortezomib (Velcade®) and dexamethasone (CVD) is an effective regimen at relapse and has emerged in recent years as the standard therapy at first relapse in the UK. Carfilzomib has good activity as a single agent in the relapsed setting, and it is expected that efficacy will be improved when used in combination with dexamethasone and cyclophosphamide...
2016: BMC Hematology
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