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relapsed multiple myeloma

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https://www.readbyqxmd.com/read/28105211/diagnostic-and-therapeutic-approaches-to-multiple-myeloma-patients-real-world-data-from-representative-multicentre-treatment-surveys-in-germany-between-2008-and-2011
#1
Thomas M Moehler, Maximilian Merz, Lenka Kellermann, Hartmut Goldschmidt, Wolfgang Knauf
A survey was conducted to investigate the standard of care for multiple myeloma in Germany, in order to clarify the status of implementation of international and national treatment guidelines. In addition, the changes in disease management over time were investigated by comparison with surveys conducted in 2008 and 2009. The survey captured a representative sample of 478 myeloma patients with a mean age of 67.9 years across various stages of the disease. Diagnostic approaches, prognostic aspects and treatment decisions were evaluated based on a survey conducted in 2011 in 58 representative centres in Germany, including university and non-university hospitals and office-based haematologists...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28099396/successful-treatment-of-refractory-langerhans-cell-histiocytosis-of-the-choroid-plexus-in-a-child-with-pulse-dexamethasone-and-lenalidomide
#2
Ramya Uppuluri, Sreejith Ramachandrakurup, Ravikanth Balaji, Divya Subburaj, Atish Bakane, Revathi Raj
Refractory/relapsed Langerhans cell histiocytosis (LCH) has a difficult course with a guarded prognosis. Salvage treatments available are both expensive and highly toxic. On the basis of the pathophysiology of LCH, we used a novel protocol including pulse dexamethasone and lenalidomide in a child with refractory LCH involving the choroid plexus, which resulted in durable remission with minimal toxicity. The protocol was extrapolated from the FIRST trial for patients with multiple myeloma. We present the clinical course, treatment protocol, and outcome in this child, who is at present disease free and in remission 18 months posttreatment...
January 17, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28092421/carfilzomib-lenalidomide-and-dexamethasone-in-patients-with-heavily-pretreated-multiple-myeloma-a-phase-1-study-in-japan
#3
Kenshi Suzuki, Masaki Ri, Takaaki Chou, Isamu Sugiura, Naoki Takezako, Kazutaka Sunami, Tadao Ishida, Tohru Izumi, Shuji Ozaki, Yoshihisa Shumiya, Kenji Ota, Shinsuke Iida
This is the first study in which the carfilzomib, lenalidomide, and dexamethasone (KRd) regimen was evaluated in heavily pretreated multiple myeloma. This study is a multicenter, open-label phase 1 study of KRd in Japanese patients with relapsed or refractory multiple myeloma (RRMM). The objectives were to evaluate the safety, tolerability, efficacy and pharmacokinetics. Carfilzomib was administrated intravenously over 10 min on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. In cycle 1, the dosage for days 1 and 2 was 20 mg/m(2) , followed by 27 mg/m(2) ...
January 16, 2017: Cancer Science
https://www.readbyqxmd.com/read/28088784/a-phase-i-clinical-study-of-autologous-dendritic-cell-therapy-in-patients-with-relapsed-or-refractory-multiple-myeloma
#4
Sung-Hoon Jung, Hyun-Ju Lee, Youn-Kyung Lee, Deok-Hwan Yang, Hyeoung-Joon Kim, Joon Haeng Rhee, Frank Emmrich, Je-Jung Lee
Cellular immunotherapy is emerging as a potential immunotherapeutic modality in multiple myeloma (MM). We have developed potent immunotherapeutic agent (VAX-DC/MM) generated by dendritic cells (DCs) loaded with autologous myeloma cells irradiated with ultraviolet B. In this study, we evaluated the safety and efficacy of VAX-DC/MM in patients with relapsed or refractory MM. This trial enrolled relapsed or refractory MM patients who had received both thalidomide- and bortezomib-based therapies. Patients received the intradermal VAX-DC/MM injection every week for 4 weeks...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28076695/deacetylase-inhibitors-an-advance-in-myeloma-therapy
#5
Jacob P Laubach, Jesus F San-Miguel, Vania Hungria, Jian Hou, Philippe Moreau, Sagar Lonial, Jae Hoon Lee, Hermann Einsele, Melissa Alsina, Paul G Richardson
A significant unmet need exists in patients with relapsed or refractory multiple myeloma (MM), which remains an incurable disease despite recent advances in the field. One such development was the use of deacetylase inhibitors (DACi), which exert unique antimyeloma effects through targeting of epigenetic and protein metabolism pathways. The pan-DACi panobinostat was recently approved in combination with bortezomib and dexamethasone for use in patients with relapsed or relapsed and refractory MM. Results of a phase 3 trial showed that the panobinostat-containing regimen improved the overall response rate and progression-free survival...
January 11, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28074071/olaptesed-pegol-an-anti-cxcl12-sdf-1-spiegelmer-%C3%A2-alone-and-with-bortezomib-dexamethasone-in-relapsed-refractory-multiple-myeloma-a-phase-iia-study
#6
H Ludwig, K Weisel, M T Petrucci, X Leleu, A M Cafro, L Garderet, C Leitgeb, R Foa, R Greil, I Yakoub-Agha, D Zboralski, S Vauléon, T Dümmler, D Beyer, Ana Kruschinski, K Riecke, M Baumann, M Engelhardt
Leukemia accepted article preview online, 11 January 2017. doi:10.1038/leu.2017.5.
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28072730/bortezomib-combined-with-lenalidomide-as-the-first-line-treatment-for-the-rare-synchronous-occurrence-of-multiple-myeloma-and-pulmonary-adenocarcinoma-a-case-report
#7
Wenli Zuo, Xinghu Zhu, Jingke Yang, Zhenyang Mei, Mei Deng, Quande Lin, Yongping Song, Qingsong Yin
BACKGROUND: Simultaneous multiple myeloma (MM) and pulmonary adenocarcinoma is a rare occurrence, and thus, treatment is a challenge. This study reports on 1 such case of MM with concurrent lung cancer, where an accurate diagnosis was made and the patient underwent treatment for both cancers. CASE SUMMARY: A 68-year-old man presented with 2 months of progressive lower back pain. Visualization with magnetic resonance imaging (MRI) revealed multiple collapsed vertebrae from T12 to S3, as well as an altered signal intensity at the T3 vertebra...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28063964/impact-of-hepatitis-b-core-antibody-hbcab-seropositivity-on-the-outcome-of-autologous-hematopoietic-stem-cell-transplantation-for-multiple-myeloma
#8
Ankur Varma, Laura Biritxinaga, Rima M Saliba, Maximilian Stich, Sarah Francesca Jauch, Aimaz Afrough, Medhavi Honhar, Uday R Popat, Mehnaz A Shafi, Nina Shah, Qaiser Bashir, Yvonne Dinh, Chitra Hosing, Richard E Champlin, Muzaffar H Qazilbash
Hepatitis B core antibody (HBcAb) seropositivity has been associated with a higher rate of hepatitis B virus (HBV) reactivation after chemotherapy, even in patients who are hepatitis B surface antigen (HBsAg) negative. However, little is known about the risk of HBV reactivation after autologous hematopoietic stem cell transplantation (auto-HCT). We evaluated the incidence of HBV reactivation, liver toxicity and survival in patients with multiple myeloma (MM) who received auto-HCT at our institution. We retrospectively identified 107 MM patients with resolved HBV infection (HBcAb positive, HBsAg negative) and 125 patients with negative HBV serology (controls) who were matched for age, timing of auto-HCT from diagnosis, cytogenetics, disease status at transplant, induction therapy, and preparative regimen...
January 4, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28061993/deferring-autologous-stem-cell-transplantation-for-consolidation-of-minimal-residual-disease-in-multiple-myeloma
#9
REVIEW
Marc Braunstein, Ruben Niesvizky
The expanding armamentarium of novel agents used in combination to treat multiple myeloma (MM) can induce clinical responses in most newly diagnosed patients, with encouraging outcomes observed in the relapsed/refractory setting. Highly sensitive techniques to detect minimal residual disease (MRD) are increasingly being employed to gauge the depth of response to modern anti-myeloma therapies and help guide therapeutic decisions. MM patients who have not achieved MRD-negativity, as assessed by one of several available assays, pose a therapeutic dilemma in terms of whether to proceed with high-dose therapy followed by autologous stem cell transplant (ASCT) versus administering additional cycles of chemotherapy...
December 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/28060563/efficacy-and-safety-of-elotuzumab-for-the-treatment-of-multiple-myeloma
#10
Maria Gavriatopoulou, Evangelos Terpos, Efstathios Kastritis, Meletios A Dimopoulos
Multiple myeloma (MM) is the second most common hematologic malignancy and despite significant outcome improvements with novel agents, the majority of patients will eventually relapse and develop treatment resistance. Immunotherapy is emerging as a promising therapeutic approach in MM. Areas covered: Elotuzumab is a monoclonal antibody directly targeting the SLAMF7 receptor, expressed on normal and malignant plasma cells. Elotuzumab has no meaningful antimyeloma activity when given as monotherapy to patients with relapsed or refractory MM (RRMM)...
January 6, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28053023/ricolinostat-the-first-selective-histone-deacetylase-6-inhibitor-in-combination-with-bortezomib-and-dexamethasone-for-relapsed-or-refractory-multiple-myeloma
#11
Dan T Vogl, Noopur S Raje, Sundar Jagannath, Paul G Richardson, Parameswaran Hari, Robert Z Orlowski, Jeffrey G Supko, David Tamang, Min Yang, Simon S Jones, Catherine Wheeler, Robert J Markelewicz, Sagar Lonial
PURPOSE: Histone deacetylase (HDAC) inhibition improves the efficacy of proteasome inhibition for multiple myeloma but adds substantial toxicity. Preclinical models suggest that the observed synergy is due to the role of HDAC6 in mediating resistance to proteasome inhibition via the aggresome/autophagy pathway of protein degradation. EXPERIMENTAL DESIGN: We conducted a phase 1/2 trial of the HDAC6-selective inhibitor ricolinostat to define the safety, preliminary efficacy, and recommended phase 2 dose in combination with standard proteasome inhibitor therapy...
January 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28050150/risk-stratification-treatment-selection-and-transplant-eligibility-in-multiple-myeloma-a-qualitative-study-of-the-perspectives-and-self-reported-practices-of-oncologists
#12
T W LeBlanc, A Howson, W Turell, P Sheldon, S C Locke, S A Tuchman, C Gasparetto, S Kaura, Z M Khan, A P Abernethy
BACKGROUND: Since the early 2000s, treatment options for multiple myeloma have rapidly expanded, adding significant complexity to the management of this disease. To our knowledge, no systematic qualitative research on clinical decision-making in multiple myeloma has been published. We sought to characterize how physicians view and implement guidelines and incorporate novel approaches into patient care. METHODS: We designed a semi-structured qualitative interview guide informed by literature review and an expert advisory panel...
December 2016: Current Oncology
https://www.readbyqxmd.com/read/28039512/efficacy-and-safety-of-autologous-hematopoietic-cell-transplantation-in-elderly-patients-with-multiple-myeloma-a-retrospective-national-multi-site-cohort-study
#13
Yael C Cohen, Tsila Zuckerman, Moshe Yeshurun, Galit Perez, Hila Magen, Israel Henig, Itai Levi, Liat Shargian, Svetlana Trestman, Uri Rouvio, Elizabeth Naparstek, Eti Ganon-Elazar, Irit Avivi, Ron Ram
We aimed to test the efficacy and toxicity of autologous hematopoietic cell transplant (HCT) in Multiple Myeloma (MM) patients aged ≥65 years compared to patients aged 60-64. Two hundred twenty consecutive patients (age ≥65, n = 87) with MM aged 60 and above, who underwent HCT as part of an upfront MM treatment, at four Israeli centers between 2000 and 2014 were included. A melphalan dose of 200 mg/m(2) was more frequent in the 60-64 age group vs. the ≥65 age group (77 vs. 57%, p = 0.002). There were no differences between groups in median day of neutrophil engraftment, incidence of infections, grades 3-4 mucositis, cardiovascular events, or non-relapse mortality at 100 days post HCT (4...
February 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28032590/predicting-the-impact-of-combined-therapies-on-myeloma-cell-growth-using-a-hybrid-multi-scale-agent-based-model
#14
Zhiwei Ji, Jing Su, Dan Wu, Huiming Peng, Weiling Zhao, Brian Nlong Zhao, Xiaobo Zhou
Multiple myeloma is a malignant still incurable plasma cell disorder. This is due to refractory disease relapse, immune impairment, and development of multi-drug resistance. The growth of malignant plasma cells is dependent on the bone marrow (BM) microenvironment and evasion of the host's anti-tumor immune response. Hence, we hypothesized that targeting tumor-stromal cell interaction and endogenous immune system in BM will potentially improve the response of multiple myeloma (MM). Therefore, we proposed a computational simulation of the myeloma development in the complicated microenvironment which includes immune cell components and bone marrow stromal cells and predicted the effects of combined treatment with multi-drugs on myeloma cell growth...
December 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/28025583/a-novel-bcma-cd3-bi-specific-t-cell-engager-for-the-treatment-of-multiple-myeloma-induces-selective-lysis-in-vitro-and-in-vivo
#15
S Hipp, Y-T Tai, D Blanset, P Deegen, J Wahl, O Thomas, B Rattel, P J Adam, K Anderson, M Friedrich
B cell maturation antigen (BCMA) is a highly plasma cell selective protein that is expressed on malignant plasma cells of multiple myeloma (MM) patients and therefore is an ideal target for T cell redirecting therapies. We developed a bispecific T cell engager (BiTE(®)) targeting BCMA and CD3ɛ (BI 836909) and studied its therapeutic impacts on MM. BI 836909 induced selective lysis of BCMA-positive MM cells, activation of T cells, release of cytokines and T cell proliferation; whereas BCMA-negative cells were not affected...
December 27, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28025582/carfilzomib-dexamethasone-vs-bortezomib-dexamethasone-in-relapsed-or-refractory-multiple-myeloma-by-cytogenetic-risk-in-the-phase-3-study-endeavor
#16
W-J Chng, H Goldschmidt, M A Dimopoulos, P Moreau, D Joshua, A Palumbo, T Facon, H Ludwig, L Pour, R Niesvizky, A Oriol, L Rosiñol, A Suvorov, G Gaidano, T Pika, K Weisel, V Goranova-Marinova, H H Gillenwater, N Mohamed, S Feng, S Aggarwal, R Hájek
The randomized phase 3 study ENDEAVOR demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for carfilzomib and dexamethasone (Kd) vs bortezomib and dexamethasone (Vd) in relapsed or refractory multiple myeloma (MM). We conducted a preplanned subgroup analysis of ENDEAVOR to evaluate Kd vs Vd by cytogenetic risk. Of 785 patients with known cytogenetics, 210 (27%) had high-risk cytogenetics (Kd, n=97 [25%]; Vd, n=113 [28%]) and 575 (73%) had standard-risk cytogenetics (Kd, n=284 [75%]; Vd, n=291 [72%])...
December 27, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28024628/polypropyleneimine-and-polyamidoamine-dendrimer-mediated-enhanced-solubilization-of-bortezomib-comparison-and-evaluation-of-mechanistic-aspects-by-thermodynamics-and-molecular-simulations
#17
Sonam Chaudhary, Avinash Gothwal, Iliyas Khan, Shubham Srivastava, Ruchi Malik, Umesh Gupta
Bortezomib (BTZ) is the first proteasome inhibitor approved by the US-FDA is majorly used for the treatment of newly diagnosed and relapsed multiple myeloma including mantle cell lymphoma. BTZ is hydrophobic in nature and is a major cause for its minimal presence as marketed formulations. The present study reports the design, development and characterization of dendrimer based formulation for the improved solubility and effectivity of bortezomib. The study also equally focuses on the mechanistic elucidation of solubilization by two types of dendrimers i...
March 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28012677/a-noninterventional-observational-registry-of-patients-with-multiple-myeloma-treated-with-lenalidomide-in-taiwan
#18
Shang-Yi Huang, Yuan-Bin Yu, Su-Peng Yeh, Tsai-Yun Chen, Woei-Yau Kao, Chih-Cheng Chen, Ming-Chung Wang, Hsuan-Yu Lin, Sheng-Fung Lin, Tseng-Hsi Lin, Ye Hua, Marie Puccio-Pick, Dena DeMarco, Christian Jacques, Po Dunn
BACKGROUND/PURPOSE: The incidence of multiple myeloma in Asia has risen in the past 30 years. Lenalidomide, an IMiD immunomodulatory agent, has improved the overall survival in patients with relapsed/refractory multiple myeloma (RRMM) when used with dexamethasone versus dexamethasone alone. This observational registry (T-CC-MM-009; NCT01752075) assessed the safety and efficacy of lenalidomide plus dexamethasone in a large Chinese population of patients with RRMM. METHODS: This registry followed the first 100 patients treated with lenalidomide plus dexamethasone in Taiwan...
December 21, 2016: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28008276/non-secretory-multiple-myeloma-from-biology-to-clinical-management
#19
REVIEW
Megan Murray Dupuis, Sascha A Tuchman
Multiple myeloma (MM) is the second most common hematologic malignancy in the US. It is typically characterized by production of large amounts of defective immunoglobulin (Ig). Diagnosing MM and monitoring treatment response, including eventual relapse, are largely based on sequential measurements of Ig. However, a small subset of MM called non-secretory multiple myeloma (NSMM) produces no detectable Ig. This subset of true NSMM has become even smaller over time, as the advent of the serum free light chain assay has resulted in the majority of NSMM patients being recategorized as light-chain MM - that is, MM cells that produce only the light-chain component of Ig...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28008160/highly-expressed-integrin-%C3%AE-8-induces-epithelial-to-mesenchymal-transition-like-features-in-multiple-myeloma-with-early-relapse
#20
Jiyeon Ryu, Youngil Koh, Hyejoo Park, Dae Yoon Kim, Dong Chan Kim, Ja Min Byun, Hyun Jung Lee, Sung-Soo Yoon
Despite recent groundbreaking advances in multiple myeloma (MM) treatment, most MM patients ultimately experience relapse, and the relapse biology is not entirely understood. To define altered gene expression in MM relapse, gene expression profiles were examined and compared among 16 MM patients grouped by 12 months progression-free survival (PFS) after autologous stem cell transplantation. To maximize the difference between prognostic groups, patients at each end of the PFS spectrum (the four with the shortest PFS and four with the longest PFS) were chosen for additional analyses...
December 2016: Molecules and Cells
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