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Multiple Myeloma, Bortezomib

Hui-Mei Guo, Li Sun, Lin Yang, Xiao-Jun Liu, Zi-Yuan Nie, Jian-Min Luo
Angiogenesis plays a significant role in the pathogenesis of multiple myeloma (MM). Microvesicles (MVs), a type of extracellular vesicles, are known as important players in cell-to-cell communication. MM-derived MVs have exhibited the activity of promoting angiogenesis. Bortezomib and lenalidomide are important drugs for treating myeloma. Therefore, the aim of the present study was to investigate whether and how MVs secreted from human myeloma cells exposed to bortezomib and lenalidomide affect angiogenesis...
April 23, 2018: Oncology Reports
Johannes M Waldschmidt, Alexander Keller, Gabriele Ihorst, Olga Grishina, Stefan Müller, Dagmar Wider, Anna V Frey, Kristina King, Roman Simon, Annette May, Pierfrancesco Tassone, Justus Duyster, Manfred Jung, Noopur Raje, Ralph Wäsch, Monika Engelhardt
This phase I/II trial was conducted to investigate the safety, efficacy, and pharmacodynamics of the pan-HDAC-inhibitor (HDACi) vorinostat combined with bortezomib, doxorubicin, and dexamethasone (VBDD) in patients suffering from relapsed/refractory multiple myeloma (RRMM). In the phase I part of this study, 9/33 patients received dose-escalated vorinostat (100, 200, 300mg), using a 4-day-on and 4-day-off schedule, and a standard 3+3 design. In the phase II part of the study, 24/33 patients were included to further assess VBDD's safety and efficacy...
April 19, 2018: Haematologica
Xu-Xia Zhang, Ling-Fang Zhang, Le Liu, Hong-Ling Li
OBJECTIVE: To explore the effect of bone marrow mesenchymal stem cells (MSC) in patients with multiple myeloma(MM) on chemotactic migration of myeloma cells in vitro. METHODS: By in vitro co-culture with diffferent MSC, the myeloma cell U266 was divided into 2 groups: group A in which the U266 cells were co-cultured with normal person MSC (N-MSC) and group B in which the U266 cells were co-cultured with MM-MSC. The expression level of CCR1 in U266 cells, migration rate of U266 cells in Transwell, and the effect of supernantant from co-culture of U266 cells with N-MSC and MM-MSC on the migration in Transwell were compared in condition with or without bortezomib...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Ling-Ling Shi, Han-Qing Li, Jian-Gang Mei, Xiao-Gang Zhou, Feng Li, Ping Song, Yong-Ping Zhai
OBJECTIVE: To investigate the effects of bortezomib(BTZ) and thalidomide(TM) on peripheral blood memory T-cells (Tm ) and regulatory T cells(Tregs) in patients with multiple myeloma(MM). METHODS: Eighty-six MM patients received 2 courses of chemotherapy were divided into effective (partial response at least) group (63 cases) and ineffective (no partial response) group (17 cases) according to therapeutic efficacy; these 80 patients were divided into BTZ group (38 cases) and TM group (42 cases) yet according to therapeutic regimens, 20 newly diagnosed MM patients were used as baseline group, 30 healthy volunteers were used as healthy control group...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Vincent L Hansen, Morton Coleman, Stephanie Elkins, Jeffrey P Letzer, Moshe Yair Levy, Lasika Seneviratne, Jessica Rine, Marina White, Emil T Kuriakose
BACKGROUND: Panobinostat was recently approved by the US Food and Drug Administration and European Commission in combination with bortezomib and dexamethasone for patients with multiple myeloma who have received ≥ 2 regimens, including bortezomib and an immunomodulatory drug. The PANEX (panobinostat expansion) treatment protocol provided access to panobinostat and gathered additional safety data before commercial availability. PATIENTS AND METHODS: In treatment phase 1, patients received panobinostat 20 mg 3 times per week plus bortezomib 1...
March 14, 2018: Clinical Lymphoma, Myeloma & Leukemia
Adeela Mushtaq, Vikas Kapoor, Azka Latif, Ahmad Iftikhar, Umar Zahid, Ali McBride, Ivo Abraham, Irbaz Bin Riaz, Faiz Anwer
Standard induction therapy for multiple myeloma is three-drug combination based on following classes of drugs: proteasome inhibitors, immunomodulators and steroids. Despite its notable efficacy, bortezomib has side effects like peripheral neuropathy (PNP) with reported incidence of grade ≥3 PNP between 2%-23% Schlafer et al., 2017. Carfilzomib (CFZ) has high selectivity and minimal off-target adverse effects including lower rates of PNP. CFZ is already approved for treatment of relapsed and refractory multiple myeloma (RRMM) as single agent as well as in combination with lenalidomide and/or dexamethasone...
May 2018: Critical Reviews in Oncology/hematology
Laurent Hudier, Olivier Decaux, Atmann Haddj-Elmrabet, Marie Lino, Lise Mandart, Pascale Siohan, Eric Renaudineau, Theophile Sawadogo, Thierry Lamy De La Chapelle, Emmanuel Oger, Frank Bridoux, Cécile Vigneau
Background: Intensive haemodialysis (IHD) in addition to bortezomib-based chemotherapy might be efficient to rapidly decrease serum immunoglobulin-free light chains removal in patients with multiple myeloma (MM) and to improve renal prognosis and survival. Methods: The aim of this retrospective multi-centre study was to compare the efficacy (renal recovery rate) of IHD and of standard haemodialysis (SHD) in patients with MM and dialysis-dependent acute kidney injury (AKI), concomitantly treated with bortezomib-based chemotherapy...
April 2018: Clinical Kidney Journal
Yan Xu, Shuhui Deng, Xuehan Mao, Gang An, Zengjun Li, Yafei Wang, Mariateresa Fulciniti, Matthew Ho, Jianhong Lin, Weiwei Sui, Wei Liu, Dehui Zou, Shuhua Yi, Wenyang Huang, Hong Liu, Rui Lv, Jian Li, Tingyu Wang, Chenxing Du, Nikhil C Munshi, Lugui Qiu
BACKGROUND: Peripheral neuropathy (PN) is an important toxicity that limits the use of bortezomib (Btz). Attempts to reduce PN have included its subcutaneous (SC) administration. PATIENTS AND METHODS: We retrospectively analyzed 307 patients with newly diagnosed multiple myeloma from a single Chinese center, receiving Btz-based regimens administered either via SC injection (SC group, n = 167) or intravenous (IV) infusion (IV group, n = 140). The efficacy and safety of Btz administration via SC and IV were then compared...
March 15, 2018: Clinical Lymphoma, Myeloma & Leukemia
Pankaj Malhotra, Uday Yanamandra, Alka Khadwal, Gaurav Prakash, Deepesh Lad, Arjun D Law, Harshit Khurana, M U S Sachdeva, Praveen Bose, Reena Das, Neelam Varma, Subhash Varma
Autologous stem cell transplantation (ASCT) is considered as standard of care in patients with multiple myeloma (MM) patients aged 65 years or younger. We analyzed data of 94 patients of plasma cell dyscrasias who underwent 95 autologous transplants at our institute from October 2003 to Aug 2016. Other than 76 patients of newly diagnosed multiple myeloma, we also transplanted two patients of POEMS syndrome, two patients of plasma cell leukemia, three patients of concurrent light chain deposition disease, three patients of multifocal plasmacytomas, and eight patients of isolated light chain myeloma...
April 2018: Indian Journal of Hematology & Blood Transfusion
Yuka Aoki, Toshiaki Hayashi, Hiroshi Ikeda, Tadao Ishida
A 77-year-old man suffering from back and arm pain was referred for anemia to the hospital by an orthopedic clinic. Serum examination of the patient revealed monoclonal IgA, and he consulted the Sapporo Medical University Hospital, where he was diagnosed with multiple myeloma complicated with AL amyloidosis. He was then enrolled for a randomized double-blind study aimed to compare between melphalan-prednisone (MP) and thalidomide-melphalan-prednisone (MPT) treatments, which revealed the patient to be in the MP arm...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Ajai Chari, Sarah Larson, Beata Holkova, Robert F Cornell, Cristina Gasparetto, Chatchada Karanes, Jeffrey V Matous, Ruben Niesvizky, Jason Valent, Matthew Lunning, Saad Z Usmani, Larry D Anderson, Lipo Chang, Yihua Lee, Yvonne Pak, Zeena Salman, Thorsten Graef, Elizabeth Bilotti, Saurabh Chhabra
This phase 1, dose-finding study investigated ibrutinib and carfilzomib ± dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma (≥2 lines of therapy including bortezomib and an immunomodulatory agent). Of 43 patients enrolled, 74% were refractory to bortezomib and 23% had high-risk cytogenetics. No dose-limiting toxicities were observed. The recommended phase 2 dose was ibrutinib 840 mg and carfilzomib 36 mg/m2 with dexamethasone. The most common ≥ grade 3 (>10%) treatment-emergent adverse events were hypertension, anemia, pneumonia, fatigue, diarrhea, and thrombocytopenia...
April 4, 2018: Leukemia & Lymphoma
Meletios Dimopoulos, Michael Wang, Vladimir Maisnar, Jiri Minarik, William Bensinger, Maria-Victoria Mateos, Mihaela Obreja, Julie Blaedel, Philippe Moreau
BACKGROUND: In ASPIRE, carfilzomib, lenalidomide, and dexamethasone (KRd) significantly improved progression-free survival (PFS) and response rates versus lenalidomide and dexamethasone (Rd) in patients with relapsed multiple myeloma. Per protocol, patients received KRd for a maximum of 18 cycles followed by Rd to progression, so the benefit/risk profile of KRd to progression was not established. METHODS: This post hoc analysis evaluated the efficacy and safety of KRd versus Rd at 18 months from randomization...
April 4, 2018: Journal of Hematology & Oncology
Ali Dehghanifard, Saeid Kaviani, Saeid Abroun, Mahshad Mehdizadeh, Sajedeh Saiedi, Amirhosein Maali, Sasan Ghaffari, Mehdi Azad
Multiple myeloma (MM) results from malignancy in plasma cells and occurs at ages > 50 years. MM is the second most common hematologic malignancy after non-Hodgkin lymphoma, which constitutes 1% of all malignancies. Despite the great advances in the discovery of useful drugs for this disease such as dexamethasone and bortezomib, it is still an incurable malignancy owing to the development of drug resistance. The tumor cells develop resistance to apoptosis, resulting in greater cell survival, and, ultimately, develop drug resistance by changing the various signaling pathways involved in cell proliferation, survival, differentiation, and apoptosis...
March 17, 2018: Clinical Lymphoma, Myeloma & Leukemia
Kwee Yong, Sebastian Gonzalez-McQuire, Zsolt Szabo, Paul Schoen, Roman Hajek
Multiple myeloma (MM) accounts for 10% of hematological cancers. Stem cell transplantation remains the cornerstone of first-line treatment for eligible patients but, historically, pharmaceutical treatment options for MM have been limited. The proteasome was identified as a target for MM therapy in the early 2000s and, in 2004, the boronic acid proteasome inhibitor bortezomib gained European approval. Bortezomib now plays a major role in MM treatment, but the duration of its use can be limited by toxicities such as peripheral neuropathy, and the development of resistance...
March 30, 2018: European Journal of Haematology
Yael C Cohen, Avi Saranga, Moshe E Gatt, Noa Lavi, Chezi Ganzel, Hila Magen, Irit Avivi, Tamar Tadmor, Celia Suriu, Osnat Jarchowsky Dolberg, Amitai Papushado, Svetlana Trestman, Ron Ram
Del17p is a genomic imbalance occurring in ∼7-10% of myeloma at diagnosis (NDMM) and comprises a poor prognostic factor. The goal of this study is to analyze real world data and outcomes among NDMM patients carrying 17p deletion. We report an observational, retrospective, multicenter study. Sixty consecutive patients diagnosed with multiple myeloma in the 8 participating centers diagnosed between 1/2008-1/2016 proven to carry 17p deletion by means of FISH were identified. Most received a bortezomib-based induction, over half underwent autologous hematopoietic cell transplantation (HCT); 30% of the patients gained early access to new novel agents via clinical trials, access programs or private insurance...
March 31, 2018: American Journal of Hematology
Mir Sadaqat Hassan Zafar, Afaq Ahmed Khan, Shyam Aggarwal, Manorama Bhargava
Background: Outcome in multiple myeloma (MM) has improved substantially over recent years as a result of the availability of multiple novel agents with acceptable safety profile. Study Design: Prospective observational study at a tertiary care institute. Methods: Twenty-five newly diagnosed patients of MM were treated with bortezomib and dexamethasone induction with monitoring for response and safety, followed by peripheral blood autologous stem cell transplant (PBASCT) in eligible patients or maintenance...
January 2018: South Asian Journal of Cancer
Ashlynn L Z Lee, Zhi Xiang Voo, Willy Chin, Robert J Ono, Chuan Yang, Shujun Gao, James L Hedrick, Yi Yan Yang
In this study, Bortezomib (BTZ, a cytotoxic water-insoluble anticancer drug) was encapsulated in micellar nanoparticles having a catechol-functionalized polycarbonate core through a pH-sensitive covalent bond between phenylboronic acid in BTZ and catechol, and these drug-loaded micelles were incorporated into hydrogels to form micelle/hydrogel composite. A series of injectable, biodegradable hydrogels with readily tunable mechanical properties were formed and optimized for sustained delivery of the BTZ-loaded micelles through ionic coacervation between phenylboronic acid-functionalized polycarbonate/poly(ethylene glycol) (PEG) 'ABA' triblock copolymer and a cationic one having guanidinium- or thiouronium-functionalized polycarbonate as 'A' block...
March 29, 2018: ACS Applied Materials & Interfaces
Atsushi Isoda, Kayoko Murayama, Shigeki Ito, Yoichi Kohara, Masaki Iino, Yuri Miyazawa, Morio Matsumoto, Hiroshi Handa, Yosuke Imai, Takuro Ishiguro, Wataru Izumita, Kiyoshi Kitano, Yukio Hirabayashi, Hideyuki Nakazawa, Fumihiro Ishida, Toru Mitsumori, Keita Kirito, Takaaki Chou, Hirokazu Murakami
In the era of novel therapeutic agents for multiple myeloma (MM), both the significance of achieving the plateau phase and the efficacy of subsequent maintenance therapy remain unclear. In the present study, we evaluated the efficacy and safety of bortezomib maintenance therapy (biweekly for 1 year) in transplant-ineligible MM patients who plateaued after bortezomib-based induction therapy. Of 36 evaluable patients, the overall response rate during induction therapy was 61%, with a stringent complete response in 6%, a complete response in 6%, a very good partial response in 17%, and a partial response in 33%...
March 28, 2018: International Journal of Hematology
Yong Won Choi, Joon Seong Park, Jae Ho Han, Jang-Hee Kim, Mi Sun Ahn, Hyun Woo Lee, Seok Yun Kang, Jin-Hyuk Choi, Seong Hyun Jeong
The predictive significance of osteolysis-related proteins was evaluated in bortezomib-treated multiple myeloma. The clinicopathological characteristics were collected retrospectively. Immunohistochemistry was performed for analyzing receptor activator of NF-κB ligand (RANKL), osteoprotegerin (OPG), macrophage inflammatory protein 1 alpha (MIP1α), and dickkopf-1 (DKK1) expression. Among clinicopatholgical characteristics, osteolytic lesion was associated with higher response to bortezomib treatment (79% vs...
March 27, 2018: Leukemia & Lymphoma
Xavier Armoiry, Martin Connock, Alexander Tsertsvadze, Ewen Cummins, G J Melendez-Torres, Pam Royle, Aileen Clarke
Ixazomib is an oral proteasome inhibitor used in combination with lenalidomide plus dexamethasone (IXA-LEN-DEX) and licensed for relapsed or refractory multiple myeloma. As part of a single technology appraisal (ID807) undertaken by the National Institute of Health and Care Excellence, the Evidence Review Group, Warwick Evidence was invited to independently review the evidence submitted by the manufacturer of ixazomib, Takeda UK Ltd. The main source of clinical effectiveness data about IXA-LEN-DEX came from the Tourmaline-MM1 randomized controlled trial in which 771 patients with relapsed or refractory multiple myeloma received either IXA-LEN-DEX or placebo-LEN-DEX as their second-, third-, or fourth-line treatment...
March 26, 2018: PharmacoEconomics
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