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Treatment of myeloma

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https://www.readbyqxmd.com/read/28454113/systematic-review-and-meta-analysis-of-the-efficacy-and-safety-of-novel-monoclonal-antibodies-for-treatment-of-relapsed-refractory-multiple-myeloma
#1
REVIEW
Tiantian Zhang, Sen Wang, Tengfei Lin, Jingmei Xie, Lina Zhao, Zhuoru Liang, Yangqiu Li, Jie Jiang
Although two newly launched monoclonal antibodies (mAbs), elotuzumab and daratumumab, performed well in patients with relapsed or relapsed/refractory multiple myeloma (RRMM), their efficacy and safety remain uncertain. We therefore performed a systematic review and meta-analysis of the most recent clinical trials that evaluated elotuzumab and/or daratumumab for the treatment of patients with RRMM. Our meta-analysis included 13 clinical trials with 2,402 patients participating. The overall response rate (ORR) was 57% (95% confidence interval [CI]: 38-76%), and the at least very good partial response rate (VGPR) was 32% (95% CI: 19-46%)...
April 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28453931/ugi-reaction-derived-%C3%AE-acyl-aminocarboxamides-bind-to-phosphatidylinositol-3-kinase-related-kinases-inhibit-hsf1-dependent-heat-shock-response-and-induce-apoptosis-in-multiple-myeloma-cells
#2
Matthias Bach, Anna Lehmann, Daniela Brünnert, Jens T Vanselow, Andreas Hartung, Ralf C Bargou, Ulrike Holzgrabe, Andreas Schlosser, Manik Chatterjee
The heat shock transcription factor 1 (HSF1) has been identified as a therapeutic target for pharmacological treatment of multiple myeloma (MM) However, direct therapeutic targeting of HSF1 function seems to be difficult due to the shortage of clinically suitable pharmacological inhibitors. We utilized the Ugi multicomponent reaction to create a small, but smart library of α-acyl aminocarboxamides, and evaluated their ability to suppress heat shock response (HSR) in MM cells. Using the INA-6 cell line as MM model, and the strictly HSF1 dependent HSP72 induction as a HSR model, we identified potential HSF1 inhibitors...
April 28, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28448171/novel-investigational-drugs-active-as-single-agents-in-multiple-myeloma
#3
Mattia D'Agostino, Marco Salvini, Antonio Palumbo, Alessandra Larocca, Francesca Gay
Multiple myeloma (MM) is a hematologic malignancy characterized by proliferation of malignant plasma cells. Patient outcome has improved markedly over the last decades due to the introduction of novel therapeutic agents such as bortezomib, thalidomide and lenalidomide. However, MM still remains largely incurable and patients eventually become refractory to available treatments. To address this unmet medical need, a variety of new molecules are currently being developed in preclinical models and/or are being investigated in clinical studies...
April 27, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28446993/minimally-invasive-surgical-techniques-for-management-of-painful-metastatic-and-primary-spinal-tumors
#4
REVIEW
Omid Hariri, Ariel Takayanagi, Dan E Miulli, Javed Siddiqi, Frank Vrionis
Patients with metastatic spinal disease are affected by disabling pain. The treatment of spinal metastases is focused on pain reduction and improvement in quality of life. Until recently, many patients with metastatic spinal disease did not qualify as surgical candidates due to the risks of surgery and length of recovery period. However, recent advances in minimally invasive surgery such as kyphoplasty and vertebroplasty allow patients to safely undergo surgery for pain relief with a short recovery period. The studies reviewed here suggest that vertebral augmentation is successful in reducing pain and disability scores in patients with painful metastases and multiple myeloma and are a safe modality to provide lasting pain relief...
March 24, 2017: Curēus
https://www.readbyqxmd.com/read/28446322/-research-advances-in-treatment-of-myeloma-nephropathy-review
#5
Xiao-Ping Zhang, Zu-Yao Xia, Bao-An Chen, Chong Gao
Myeloma nephropathy is a common complication in patients with myltiple myeloma (MM) that causes high morbidity. In the majority of cases, renal impairment is caused by the accumulation and precipitation of light chains, which form casts in the distal tubules, resulting in renal obstruction. This review discusses the recent advances on its treatment, so as to provide reference for clinical treatment of MM induced-renal failure.
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28446300/-clinical-value-of-serum-fructosamine-measurement-in-iga-type-multiple-myeloma
#6
Jing-Yu Zhang, Hong Fan, Li-Xin Chen, Li-Fang Wang, Hong-Fei Wang, Hai-Xiang Shi
OBJECTIVE: To investigate the value of serum fructosamine (FMN) measurement in clinical typing and staging of multiple myeloma(MM) as well as evaluation of curative efficacy and prognosis of IgA type MM. METHODS: The levels of FMN were detected by nitro-blue-tetrazolium colorimetric method in 62 IgA type MM patients, 65 IgG type MM patients, 24 IgM type MM patients. The difference between the serum FMN levels and different MM types and its relationship with IgA type MM, patients' stages, efficacy and as well as, the effect of FMN level on overall survival (OS) time of IgA type MM patients were analyzed...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28446297/-prophylaxis-of-bortezomib-induced-peripheral-neuropathy-in-patients-with-multiple-myeloma-by-high-dose-intravenous-mecobalamin
#7
Li-Li Zhang, Yi-Hao Wang, Zong-Hong Shao, Jun Ma
OBJECTIVE: To evaluate the efficacy and safety of high-dose intravenous mecobalamin (HDIME) for the treatment of bortezomib-induced peripheral neuropathy(BIPN) in the patients with multiple myeloma (MM). METHODS: A total of 65 newly diagonsed patients with multiple myeloma receiving bortezomib in Tianjin Medical University General Hospital were enrolled in this single-centre randomized clinical trial from July 2012 to May 2016. Out of 65 patients 38 in control group received bortezomib-based chemotherapy and 27 patients in HDIME group received the additional high-dose intravenous mecobalamin...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28446294/-effect-of-hedgehog-signaling-pathway-abnormality-on-chemothe-rapeutic-resistance-of-multiple-myeloma
#8
Jia-Sheng Hu, Xiao Huang, Ying-Dan Huang, Yan-Yan Lu, Quan-Yi Lu
OBJECTIVE: To study the correlation between the excessive activation of Hedgehog signal and the drug resistance of multiple myeloma. METHODS: The resistant cell line RPMI 8226/R of multiple myeloma was established by an ascending concentration gradient method. The experiment consisted of 4 groups: RPMI8226/R, RPMI8226/S, GANT61+RPMI8226/R and GANT61+RPMI8226/S. The CCK-8 (cell counting kit-8) assay was used to detect the cell proliferation inhibition rate in 4 groups; the RT-PCR was used to detect the expression of Gli1, Gli2, Shh, Ihh, Smo and Sufu in the RPMI8226/S and RPMI8226/R cells...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28442888/new-developments-in-the-treatment-of-multiple-myeloma-clinical-utility-of-daratumumab
#9
REVIEW
Cian McEllistrim, Janusz Krawczyk, Michael E O'Dwyer
Multiple myeloma is a clonal disorder of plasma cells that is currently considered incurable. CD38 is a 46 kDa type II transmembrane glycoprotein that is highly expressed on myeloma cells. Daratumumab is a first in-class human IgG1 monoclonal antibody that targets CD38, and has antimyeloma effects through several mechanisms. Single-agent trials show surprising activity in heavily pretreated myeloma patients. Trials in the relapsed setting, where daratumumab is added to lenalidomide and dexamethasone or bortezomib and dexamethasone, have demonstrated significantly improved progression-free survival with acceptable toxicity...
2017: Biologics: Targets & Therapy
https://www.readbyqxmd.com/read/28441582/synthesis-and-antiproteasomal-activity-of-novel-o-benzyl-salicylamide-based-inhibitors-built-from-leucine-and-phenylalanine
#10
Radek Jorda, Jan Dušek, Eva Řezníčková, Karel Pauk, Pratibha P Magar, Aleš Imramovský, Vladimír Kryštof
Inhibition of protein degradation is one of strategies for suppression of uncontrolled proliferation of cancer cells. Proteolytic degradation in cells is mainly ensured by proteasome and its inhibition by bortezomib showed benefit in clinical use for the treatment of multiple myeloma. We report here the library of antiproteasomal O-benzyl salicylamides built from leucine and phenylalanine. Prepared compounds displayed antiproliferative activity on K562, CEM and U266 cancer cell lines, ranging from high micromolar to submicromolar GI50 values...
April 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28439875/epigenetic-repression-of-mir-375-is-the-dominant-mechanism-for-constitutive-activation-of-the-pdpk1-rps6ka3-signalling-axis-in-multiple-myeloma
#11
Shotaro Tatekawa, Yoshiaki Chinen, Masaki Ri, Tomoko Narita, Yuji Shimura, Yayoi Matsumura-Kimoto, Taku Tsukamoto, Tsutomu Kobayashi, Eri Kawata, Nobuhiko Uoshima, Tomohiko Taki, Masafumi Taniwaki, Hiroshi Handa, Shinsuke Iida, Junya Kuroda
Cytogenetic/molecular heterogeneity is the hallmark of multiple myeloma (MM). However, we recently showed that the serine/threonine kinase PDPK1 and its substrate RPS6KA3 (also termed RSK2) are universally active in MM, and play pivotal roles in myeloma pathophysiology. In this study, we assessed involvement of aberrant miR-375 repression in PDPK1 overexpression in MM. An analysis of plasma cells from 30 pre-malignant monoclonal gammopathies of undetermined significance and 73 MM patients showed a significant decrease in miR-375 expression in patient-derived plasma cells regardless of the clinical stage, compared to normal plasma cells...
April 25, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28439700/filgrastim-alone-versus-pegylated-filgrastim-alone-for-autologous-peripheral-blood-stem-cells-mobilization-in-newly-diagnosed-multiple-myeloma-patients
#12
Barbara Skopec, Matevz Skerget, Darja Zontar, Vesna Zadnik, Samo Zver
BACKGROUND: Autologous hematopoietic stem cell transplantation (aHSCT) is the recommended standard upfront treatment for transplant eligible myeloma patients. Considering possible complications related to chemotherapy-cytokine mobilization, cytokine-alone mobilization is often used. We compared mobilization with filgrastim alone to pegfilgrastim alone in newly diagnosed myeloma patients after induction treatment with bortezomib and dexamethasone. The comparison was made between peripheral blood stem cell (PBSC) yields, number of apheresis, hematopoietic stem cell subsets, and time to neutrophil and platelet engraftment after aHSCT...
April 24, 2017: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/28439109/efficacy-and-safety-of-carfilzomib-regimens-in-multiple-myeloma-patients-relapsing-after-autologous-stem-cell-transplant-aspire-and-endeavor-outcomes
#13
P Hari, M-V Mateos, R Abonour, S Knop, W Bensinger, H Ludwig, K Song, R Hajek, P Moreau, D S Siegel, S Feng, M Obreja, S K Aggarwal, K Iskander, H Goldschmidt
Autologous stem cell transplantation (ASCT) is a standard treatment for eligible multiple myeloma (MM) patients, but many patients will relapse after ASCT and require subsequent therapy. The proteasome inhibitor carfilzomib is approved for relapsed or refractory MM (RRMM). In phase 3 trials, carfilzomib-based regimens (ASPIRE, carfilzomib-lenalidomide-dexamethasone; ENDEAVOR, carfilzomib-dexamethasone) demonstrated superior progression-free survival (PFS) compared with standard therapies for RRMM (ASPIRE: lenalidomide-dexamethasone; ENDEAVOR, bortezomib-dexamethasone)...
April 25, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28439108/phase-i-trial-of-systemic-administration-of-edmonston-strain-of-measles-virus-genetically-engineered-to-express-the-sodium-iodide-symporter-in-patients-with-recurrent-or-refractory-multiple-myeloma
#14
A Dispenzieri, C Tong, B LaPlant, M Q Lacy, K Laumann, D Dingli, Y Zhou, M J Federspiel, M A Gertz, S Hayman, F Buadi, M O'Connor, V J Lowe, K-W Peng, S J Russell
MV-NIS is an Edmonston-lineage oncolytic measles virus expressing the human sodium-iodide symporter--a means for monitoring by noninvasive imaging of radioiodine. Patients with relapsed, refractory myeloma who had explored all other treatment options were eligible for this Phase I trial. Cohort 1 was treated with intravenous MV-NIS, and Cohort 2 received cyclophosphamide two days prior to MV-NIS. Thirty-two patients were treated. Cohort 1 initially enrolled to 4 dose-levels without reaching MTD and subsequently to 2 higher dose-levels when improved virus manufacture technology made it possible...
April 25, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28436378/outcomes-of-corpectomy-in-patients-with-metastatic-cancer
#15
Grzegorz Guzik
BACKGROUND: The objective of surgical management of spinal metastases is to reduce pain and improve the patient's quality of life. The operation should restore spinal stability and decompress neural structures. One surgical technique is corpectomy followed by vertebral body reconstruction and stabilisation of the spine. The procedure may be performed in patients in overall good health and a good survival prognosis. The aim of this paper is to present the outcomes of surgical management of spinal metastases in patients who underwent corpectomy followed by vertebral body reconstruction and stabilisation of the spine...
January 26, 2017: Ortopedia, Traumatologia, Rehabilitacja
https://www.readbyqxmd.com/read/28435287/serum-galectin-1-in-patients-with-multiple-myeloma-associations-with-survival-angiogenesis-and-biomarkers-of-macrophage-activation
#16
Morten Nørgaard Andersen, Maja Ludvigsen, Niels Abildgaard, Irma Petruskevicius, Rikke Hjortebjerg, Mette Bjerre, Bent Honoré, Holger J Møller, Niels F Andersen
Galectin-1 (Gal-1) is known to regulate cell signaling within the immune system and may be a target for new anticancer immune therapy. In patients with chronic lymphocytic leukemia (CLL) and classical Hodgkin lymphoma (cHL), high levels of Gal-1 within the tumor microenvironment were associated with worse disease state or poor outcome. Gal-1 can be secreted from cells by an unknown mechanism, and levels in blood samples were associated with high tumor burden and worse disease state in cHL and CLL patients. However, serum levels of Gal-1 have never been investigated in patients with multiple myeloma (MM)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28434927/impact-of-autologous-stem-cell-transplantation-on-the-incidence-and-outcome-of-oligoclonal-bands-in-patients-with-light-chain-amyloidosis
#17
Luis Gerardo Rodríguez-Lobato, Carlos Fernández de Larrea, M Teresa Cibeira, Natalia Tovar, Juan I Aróstegui, Laura Rosiñol, Tania Díaz, Ester Lozano, Montserrat Elena, Jordi Yagüe, Joan Bladé
The emergence of oligoclonal bands (OB) in patients with multiple myeloma achieving a complete remission (CR) after autologous stem cell transplantation (ASCT) and the use of novel agents is a well-recognized event. The presence of OB is associated with favorable outcome. However, the emergence of OB in light-chain (AL) amyloidosis has never been investigated. The aim of the study was to determine the incidence, natural history and prognostic impact of OB in 50 patients with AL amyloidosis who achieved at least a partial response (PR) either after up-front ASCT (20 patients [40%]) or after conventional treatment in patients ineligible for transplant (30 patients [60%])...
April 18, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28434255/daratumumab-for-the-treatment-of-multiple-myeloma
#18
Cyrille Touzeau, Philippe Moreau
Proteasome inhibitors and immunomodulatory drugs have contributed to the dramatic improvement in survival for patients with myeloma over the past decades. However, the disease typically relapses and new classes of drugs are needed. In 2015, two monoclonal antibodies were approved for the treatment of patients with relapsed multiple myeloma, and immunotherapy has rapidly become indispensable in the management of myeloma patients. Areas covered: Here, the authors discuss the published data regarding the mechanism of action, safety and clinical efficacy of the CD38-targeted monoclonal antibody daratumumab for the treatment of patients with multiple myeloma...
April 24, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28431262/immunologic-approaches-for-the-treatment-of-multiple-myeloma
#19
REVIEW
Leo Rasche, Niels Weinhold, Gareth J Morgan, Frits van Rhee, Faith E Davies
The FDA approval of two monoclonal antibodies in 2015has heralded a new era of targeted immunotherapies for multiple myeloma (MM). In this review we discuss the recent approaches using different immunological components to treat MM. In particular, we review current monoclonal antibody based therapies, engineered T- and NK cell products, 'off-target' immunomodulation, and strategies utilizing allogeneic cell transplantation in MM. We discuss how an immunologic approach offers promise for the treatment of this genetically heterogeneous disease, and how patients with acquired drug resistance may particularly benefit from these therapies...
April 6, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28430745/bortezomib-pharmacokinetics-in-tumor-response-and-peripheral-neuropathy-in-multiple-myeloma-patients-receiving-bortezomib-containing-therapy
#20
Sung-Eun Lee, Kyungmee Choi, Seunghoon Han, Jongtae Lee, Taegon Hong, Gab-Jin Park, Dong-Seok Yim, Chang-Ki Min
The usefulness of pharmacokinetics of bortezomib for multiple myeloma (MM) with respect to the maximum response to bortezomib and bortezomib-induced peripheral neuropathy (BIPN) development was studied. Maximum response to subcutaneous bortezomib therapy and BIPN occurrence for the first 12 weeks of treatment in 35 MM patients treated by bortezomib-dexamethasone (VD) and bortezomib-melphalan-prednisone (VMP) were evaluated. On day 1 of cycle 1, seven whole-blood samples were collected for 3 h after dosing completion to obtain the maximum plasma concentration and area under the time-concentration curve during 3 h postdose (AUC0-3) in each patient...
April 20, 2017: Anti-cancer Drugs
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