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https://www.readbyqxmd.com/read/29453884/daratumumab-resistance-is-frequent-in-advanced-stage-multiple-myeloma-patients-irrespectively-of-cd38-expression-and-is-related-to-dismal-prognosis
#1
M Pick, V Vainstein, N Goldschmidt, D Lavie, D Libster, A Gural, S Grisariu, B Avni, D Ben Yehuda, M E Gatt
OBJECTIVE: Daratumumab is a promising new anti-myeloma agent. We report a single center "real world" series of multiple myeloma (MM) and amyloidosis (AL) patients treated with daratumumab. METHODS: Forty-one patients were included: 7 second line MM, 30 heavily pretreated (median number of therapies of 5) advanced MM, and 4 with AL. RESULTS: Second line patients and advanced AL showed high rate of durable overall responses. However, advanced MM patients had a dismal prognosis with an ORR of 36%, and a short median progression free and overall survival of 2...
February 17, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29453626/drug-approval-based-on-randomized-phase-3-trials-for-relapsed-malignancy-analysis-of-oncologic-drugs-granted-accelerated-approval-publications-and-clinical-trial-databases
#2
Sumimasa Nagai, Keiya Ozawa
Background As relapsed disease is frequently the first target of newly developed therapies, it is vital to address the difficulty in demonstrating the efficacy of new drugs for relapsed malignancy in randomized phase 3 trials. Methods We analyzed the approved indications, target populations, and development status of post-marketing confirmatory trials of all oncology-related drugs that were granted accelerated approval for both hematological and solid malignancies. Furthermore, we searched for randomized phase 3 trials for adult patients with relapsed lymphoid malignancy, other than chronic lymphocytic leukemia (CLL) and multiple myeloma (MM)...
February 17, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29453220/identification-of-novel-fusion-transcripts-in-multiple-myeloma
#3
Mingxuan Lin, Peak Ling Lee, Lily Chiu, Constance Chua, Kenneth H K Ban, Adeline H F Lin, Zit Liang Chan, Tae-Hoon Chung, Benedict Yan, Wee-Joo Chng
AIMS: Multiple myeloma (MM) is a heterogeneous disease characterised by genetically complex abnormalities. The classical mutational spectrum includes recurrent chromosomal aberrations and gene-level mutations. Recurrent translocations involving the IGH gene such as t(11;14), t(4;14) and t(14;16) are well known. However, the presence of complex genetic abnormalities raises the possibility that fusions other than the recurrent IGH translocations exist. We therefore employed a targeted RNA-sequencing panel to identify novel putative fusions in a local cohort of MM...
February 16, 2018: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29452082/pre-treatment-red-blood-cell-distribution-width-provides-prognostic-information-in-multiple-myeloma
#4
Di Zhou, Peipei Xu, Miaoxin Peng, Xiaoyan Shao, Miao Wang, Jian Ouyang, Bing Chen
BACKGROUND: The red blood cell distribution width (RDW), a credible marker for abnormal erythropoiesis, has recently been studied as a prognostic factor in oncology, but its role in multiple myeloma (MM) hasn't been thoroughly investigated. METHODS: We performed a retrospective study in 162 patients with multiple myeloma. Categorical parameters were analyzed using Pearson chi-squared test. The Mann-Whitney and Wilcoxon tests were used for group comparisons. Comparisons of repeated samples data were analyzed with the general linear model repeated-measures procedure...
February 13, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29450683/common-adverse-effects-of-novel-therapies-for-multiple-myeloma-mm-and-their-management-strategies
#5
REVIEW
Kristen B McCullough, Miriam A Hobbs, Jithma P Abeykoon, Prashant Kapoor
PURPOSE OF REVIEW: The purpose of this review was to evaluate management strategies for common adverse effects of novel therapies in multiple myeloma (MM), including immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies, and a histone deacetylase inhibitor. RECENT FINDINGS: There are several adverse effects that occur across multiple classes of antimyeloma drugs, including rash, peripheral neuropathy, infusion reactions, and cardiotoxicity, but most can be managed without complete discontinuation of the agent or abandonment of the class...
February 15, 2018: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29450644/pi3k-akt-inhibitor-ly294002-potentiates-homoharringtonine-antimyeloma-activity-in-myeloma-cells-adhered-to-stromal-cells-and-in-scid-mouse-xenograft
#6
Ping Chen, Xiaofang Wen, Bin Wang, Diyu Hou, Hong Zou, Qin Yuan, Hui Yang, Jieqiong Xie, Huifang Huang
Homoharringtonine (HHT) is a known anti-leukemia drug that inhibits multiple myeloma (MM) cells both in vitro and in vivo. Our prior study demonstrated that the potency of HHT in MM cells was compromised significantly when myeloma cells were co-cultured with BM stromal cells. This study aimed to investigate whether PI3K/Akt inhibitor LY294002 could potentiate the antimyeloma activity of HHT against MM cells adhered to BM stromal cells and in vivo xenograft models. A co-culture system composed of MM cells and human stromal cells was employed to mimic MM cells in bone marrow niche...
February 15, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29450620/targeting-the-neddylation-pathway-in-cells-as-a-potential-therapeutic-approach-for-diseases
#7
REVIEW
Jie Ying, Miaomiao Zhang, Xiaoyan Qiu, Yu Lu
The ubiquitin-proteasome system (UPS) is an important system that regulates the balance of intracellular proteins, and it is involved in the regulation of multiple vital biological processes. The approval of bortezomib for relapsed and refractory multiple myeloma has proven that agents targeting the UPS have the potential to be effective treatment strategies for diseases. Among of all of the components of the UPS, cullin-RING ligases (CRLs) are the focus of research. CRLs are the largest family of ubiquitin E3 ligases and they play a critical role in substrate binding...
February 15, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29450576/immunopet-imaging-of-cd38-in-murine-lymphoma-models-using-89-zr-labeled-daratumumab
#8
Lei Kang, Dawei Jiang, Christopher G England, Todd E Barnhart, Bo Yu, Zachary T Rosenkrans, Rongfu Wang, Jonathan W Engle, Xiaojie Xu, Peng Huang, Weibo Cai
PURPOSE: CD38 is considered a potential biomarker for multiple myeloma (MM) and has shown a strong link with chronic lymphocytic leukemia due to high and uniform expression on plasma cells. In vivo evaluation of CD38 expression may provide useful information about lesion detection and prognosis of treatment in MM. In this study, immunoPET imaging with 89 Zr-labeled daratumumab was used for differentiation of CD38 expression in murine lymphoma models to provide a potential non-invasive method for monitoring CD38 in the clinic...
February 15, 2018: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29448111/in-silico-screening-of-proteins-targeting-circulating-mirnas-for-improved-diagnosis-of-multiple-myeloma
#9
Shradha Suyal, Manish Pratap Singh, Himanshu Shekhar, Sameer Srivastava
Multiple Myeloma (MM) is a B-cell malignancy, which is characterized by the expansion of clonal plasma cells in the bone marrow, leading to abnormal accumulation of monoclonal antibodies in circulation. Certain circulating miRNAs are deregulated in MM and their differential expression profiles in body fluids can be quantified and used discriminate between the premalignant and malignant stages of MM. Our study identifies protein which would show affinity for a selected panel of circulating miRNAs deregulated in MM...
February 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29448055/proteomic-characterization-of-withaferin-a-targeted-protein-networks-for-the-treatment-of-monoclonal-myeloma-gammopathies
#10
Martin Dom, Fritz Offner, Wim Vanden Berghe, Xaveer Van Ostade
Withaferin A (WA), a natural steroid lactone from the plant Withania somnifera, is often studied because of its antitumor properties. Although many in vitro and in vivo studies have been performed, the identification of Withaferin A protein targets and its mechanism of antitumor action remain incomplete. We used quantitative chemoproteomics and differential protein expression analysis to characterize the WA antitumor effects on a multiple myeloma cell model. Identified relevant targets were further validated by Ingenuity Pathway Analysis and Western blot and indicate that WA targets protein networks that are specific for monoclonal gammopathy of undetermined significance (MGUS) and other closely related disorders, such as multiple myeloma (MM) and Waldenström macroglobulinemia (WM)...
February 12, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29446103/carfilzomib-in-relapsed-or-refractory-multiple-myeloma-patients-with-early-or-late-relapse-following-prior-therapy-a-subgroup-analysis-of-the-randomized-phase-3-aspire-and-endeavor-trials
#11
Maria-Victoria Mateos, Hartmut Goldschmidt, Jesus San-Miguel, Joseph Mikhael, Lucy DeCosta, Lifen Zhou, Mihaela Obreja, Julie Blaedel, Zsolt Szabo, Xavier Leleu
We performed analyses of the randomized phase 3 ASPIRE and ENDEAVOR trials to investigate the efficacy of carfilzomib among subgroups of relapsed or refractory multiple myeloma patients who had early or late disease relapse following initiation of the immediately prior therapy. In ASPIRE and ENDEAVOR, patients had received 1 to 3 prior lines of therapy. Patients in ASPIRE received carfilzomib, lenalidomide, and dexamethasone (KRd) or lenalidomide and dexamethasone (Rd), and patients in ENDEAVOR received carfilzomib and dexamethasone (Kd) or bortezomib and dexamethasone (Vd)...
February 15, 2018: Hematological Oncology
https://www.readbyqxmd.com/read/29445583/deep-sustained-response-to-daratumumab-monotherapy-associated-with-t-cell-expansion-in-triple-refractory-myeloma
#12
Saad Z Usmani, Imran Khan, Christopher Chiu, David Foureau, Lawrence J Druhan, Katherine Rigby, Tineke Casneuf, A Kate Sasser
Background: Daratumumab, a human CD38 monoclonal antibody that has direct on-tumor and immunomodulatory mechanisms of action, demonstrated clinical benefit as monotherapy or in combination with established regimens in patients with multiple myeloma with one or more prior lines of therapy. Case presentation: A male patient, who was 70 years of age at the time of diagnosis of multiple myeloma in 2011, relapsed after five lines of therapy, including autologous stem cell transplantation...
2018: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29445483/lenalidomide-decreased-the-psa-level-for-castration-resistant-prostate-cancer-a-case-report
#13
Kota Shimokihara, Takashi Kawahara, Taisei Suzuki, Taku Mochizuki, Daiji Takamoto, Jun-Ichi Teranishi, Yasuhide Miyoshi, Yasushi Yumura, Masahiro Yao, Hiroji Uemura
Lenalidomide has been developed as the derivative of thalidomide that has fewer side effects. We herein report a rare case of castration-resistant prostate cancer successfully maintained using lenalidomide for multiple myeloma.
February 2018: Clinical Case Reports
https://www.readbyqxmd.com/read/29445461/metastatic-prostate-cancer-with-bone-marrow-infiltration-mimicking-multiple-myeloma
#14
Pankaj Mathur, Daisy Alapat, Manoj Kumar, Sharmilan Thanendrarajan
Concomitant diagnosis of metastatic prostate cancer and a multiple myeloma in older male patients is challenging as both malignancies are usually associated with bone lesions. Exact knowledge, experience, and an interdisciplinary approach are required in order to differentiate between both malignancies and determine the exact treatment strategy.
February 2018: Clinical Case Reports
https://www.readbyqxmd.com/read/29445457/prostate-carcinoma-presenting-with-diffuse-osteolytic-metastases-and-supraclavicular-lymphadenopathy-mimicking-multiple-myeloma
#15
Bukunmi Michael Idowu
Prostate cancer typically presents with osteoblastic metastases; however, patients with prostate cancer may have osteolytic metastases, as seen in this case. Patients with osteolytic metastases require a thorough evaluation to rule out malignancies including multiple myeloma, but prostate cancer is a very important differential diagnosis.
February 2018: Clinical Case Reports
https://www.readbyqxmd.com/read/29445026/panobinostat-and-multiple-myeloma-in-2018
#16
Andrew J Yee, Noopur S Raje
No abstract text is available yet for this article.
February 14, 2018: Oncologist
https://www.readbyqxmd.com/read/29444873/hypoxia-inducible-kdm3a-addiction-in-multiple-myeloma
#17
Sho Ikeda, Akihiro Kitadate, Fumito Abe, Naoto Takahashi, Hiroyuki Tagawa
In multiple myeloma (MM), the bone marrow (BM) microenvironment may contain a myeloma cell fraction that has acquired treatment resistance by undergoing an epigenetic gene expression change. Hypoxic stress is an important factor in the BM microenvironment. Recently, we demonstrated that miR-210 was upregulated in hypoxia and downregulated IRF4, which is known as an essential factor in myeloma oncogenesis in normoxia. In the study, we demonstrated that myeloma cells still showed a strong antiapoptotic phenotype despite IRF4 downregulation, suggesting that another antiapoptotic factor might be involved under hypoxic stress...
February 27, 2018: Blood Advances
https://www.readbyqxmd.com/read/29444632/immunohistochemical-labeling-of-multiple-myeloma-oncogene-1-interferon-regulatory-factor-4-mum1-irf-4-in-canine-cutaneous-histiocytoma
#18
Justin M Stilwell, Daniel R Rissi
Multiple myeloma oncogene 1/interferon regulatory factor 4 (MUM1/IRF-4) immunohistochemistry (IHC) is mainly used for diagnostic confirmation of plasma cell tumors (PCTs) in dogs and cats. This article describes MUM1/IRF-4 IHC expression in 20 cases of canine cutaneous histiocytoma (CH) and compares it with 10 cutaneous or mucocutaneous PCTs and 5 cutaneous histiocytic sarcomas (HSs) submitted to the same IHC protocol. All histiocytomas had strong nuclear and variable cytoplasmic immunolabeling for MUM1/IRF-4, whereas all PCTs had strong nuclear and moderate cytoplasmic immunolabeling for MUM1/IRF-4...
January 1, 2018: Veterinary Pathology
https://www.readbyqxmd.com/read/29444503/whither-the-bone-marrow-transplantation-in-multiple-myeloma
#19
Guillermo J Ruiz-Argüelles
No abstract text is available yet for this article.
February 14, 2018: Acta Haematologica
https://www.readbyqxmd.com/read/29444353/healthcare-resource-utilisation-associated-with-skeletal-related-events-in-european-patients-with-multiple-myeloma-results-from-a-prospective-multinational-observational-study
#20
John Ashcroft, Ignacio Duran, Herbert Hoefeler, Vito Lorusso, Diana Lueftner, Marco Campioni, Michele Intorcia, Amit Bahl
OBJECTIVES: Patients with multiple myeloma (MM) often experience debilitating skeletal-related events (SREs: pathologic fracture, radiation to bone [RB], surgery to bone [SB] or spinal cord compression [SCC]). This is the first comprehensive, prospective, observational analysis of healthcare resource utilisation (HRU), independently attributed to SREs by investigators, in patients with MM. METHODS: Eligible patients had lytic bone lesions, life expectancy ≥6 months, Eastern Cooperative Oncology Group performance status ≤2, and ≥1 SRE in the 97 days before enrolment...
February 14, 2018: European Journal of Haematology
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