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https://www.readbyqxmd.com/read/28723635/meta-analysis-of-the-efficacy-of-treatments-for-newly-diagnosed-and-relapsed-refractory-multiple-myeloma-with-del-17p
#1
Jinghua Liu, Hui Yang, Xiaochan Liang, Yuxin Wang, Jian Hou, Yanqin Liu, Jigang Wang, Fan Zhou
We analyzed the treatment of newly diagnosed and relapsed/refractory multiple myeloma (NDMM/RRMM) patients with del(17p). Thirteen prospective studies that evaluated 3,187 MM patients, including 685with del(17p), were included in our meta-analysis. The incidence of del(17p) in NDMM and RRMM patients was similar (13% vs. 14%, respectively, P = 0.64, I2 = 94%). The overall response rate (ORR) to new agents was 40.5% and 67.1%, respectively, in RRMM patients with or without del(17p) (P = 0.1, I2 = 63.9%). NDMM patients with del(17p) treated with PAD (bortezomib, adriamycin, and dexamethasone) induction therapy followed by bortezomib maintenance therapy had higher progression-free survival (PFS) (25...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28711728/allogeneic-blood-or-marrow-transplantation-with-post-transplantation-cyclophosphamide-as-graft-versus-host-disease-prophylaxis-in-multiple-myeloma
#2
Nilanjan Ghosh, Xiaobu Ye, Hua-Ling Tsai, Javier Bolaños-Meade, Ephraim J Fuchs, Leo Luznik, Lode J Swinnen, Douglas E Gladstone, Richard F Ambinder, Ravi Varadhan, Satish Shanbhag, Robert A Brodsky, Ivan M Borrello, Richard J Jones, William Matsui, Carol Ann Huff
Allogeneic blood or marrow transplantation (alloBMT) may lead to long-term disease control in patients with multiple myeloma (MM). However, historically, the use of alloBMT in MM has been limited by its high non-relapse mortality (NRM) rates primarily from graft versus host disease (GVHD). We previously demonstrated that post-transplantation cyclophosphamide (PTCy) decreases the toxicities of both acute and chronic GVHD rates following alloBMT. Here we examine the impact of PTCy in MM patients undergoing alloBMT at Johns Hopkins Hospital...
July 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28706008/efficacy-and-safety-of-bortezomib-maintenance-in-patients-with-newly-diagnosed-multiple-myeloma-a-meta-analysis
#3
Chun-Yan Sun, Jun-Ying Li, Zhang-Bo Chu, Lu Zhang, Lei Chen, Yu Hu
Multiple myeloma (MM) is a B-cell neoplasm with a high incidence of relapse. Bortezomib has been extensively studied for the maintenance treatment of MM. Here we carried out a meta-analysis to determine the efficacy and safety of maintenance therapy with bortezomib. We searched for clinical trials in PubMed (Medline), Embase (OVID) and the Cochrane Library. Two randomized controlled trials (RCTs) enrolling a total of 1338 patients were included. Bortezomib maintenance statistically significantly improved both PFS (HR 0...
July 13, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28693058/-a-prospective-multi-center-trial-of-non-interventional-and-observational-study-of-lenalidomide-in-chinese-patients-with-multiple-myeloma
#4
G M Wang, G Z Yang, Z X Huang, Y P Zhong, F Y Jin, A J Liao, X M Wang, Z Z Fu, H Liu, X L Li, J F Zhou, X Zhang, Y Hu, F Y Meng, X J Huang, W M Chen, J Lu
Objective: To evaluate the efficacy and safety of lenalidomide in a real-world clinical practice in Chinese patients with multiple myeloma (MM). Methods: It was a prospective, multi-center, observational study. A total of 165 consecutive patients with MM treated with lenalidomide-based regimens were enrolled in 12 hospitals from June 2013 to November 2015. Relevant information was recorded, such as baseline clinical data, cytogenetic abnormalities, treatment regimens, and duration of treatment, safety, and survival...
July 1, 2017: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/28692028/in-search-of-the-optimal-platform-for-post-allogeneic-sct-immunotherapy-in-relapsed-multiple-myeloma-a-systematic-review
#5
REVIEW
R Oostvogels, S M U Venema, M de Witte, R Raymakers, J Kuball, N Kröger, M C Minnema
Allogeneic stem cell transplantation (allo-SCT) has the potential to induce sustained remissions in patients with multiple myeloma (MM). Currently, allo-SCT is primarily performed in high-risk MM patients, most often in the setting of early relapse after first-line therapy with autologous SCT. However, the implementation of allo-SCT for MM is jeopardized by high treatment-related mortality (TRM) rates as well as high relapse rates. In this systematic review, we aimed to identify a safe allo-SCT strategy that has optimal 1-year results regarding mortality, relapse and severe GvHD, creating opportunities for post-transplantation strategies to maintain remissions in the high-risk group of relapsed MM patients...
July 10, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28685821/pd-1-pd-l1-inhibitors-in-haematological-malignancies-update-2017
#6
REVIEW
Tomas Jelinek, Jana Mihalyova, Michal Kascak, Juraj Duras, Roman Hajek
The introduction of PD-1/PD-L1 pathway inhibitors is an important landmark in solid oncology with unprecedented practice-changing activity in various types of solid tumours. Amongst haematological malignancies, PD-1/PD-L1 inhibitors have been successful, so far, only in the treatment of classical Hodgkin lymphoma, which typically exhibits an over-expression of PD-1 ligands (PD-L1, PD-L2) due to alterations in chromosome 9p24.1. Such positive outcomes led to the FDA approval of nivolumab use in relapsed Hodgkin lymphoma in 2016 as the first haematological indication...
July 6, 2017: Immunology
https://www.readbyqxmd.com/read/28684537/pomalidomide-bortezomib-and-dexamethasone-pvd-for-patients-with-relapsed-lenalidomide-refractory-multiple-myeloma
#7
Jonas Paludo, Joseph R Mikhael, Betsy R LaPlant, Alese E Halvorson, Shaji Kumar, Morie A Gertz, Suzanne R Hayman, Francis K Buadi, Angela Dispenzieri, John A Lust, Prashant Kapoor, Nelson Leung, Stephen J Russell, David Dingli, Ronald S Go, Yi Lin, Wilson I Gonsalves, Rafael Fonseca, P Leif Bergsagel, Vivek Roy, Taimur Sher, Asher A Chanan-Khan, Sikander Ailawadhi, A Keith Stewart, Craig B Reeder, Paul G Richardson, S Vincent Rajkumar, Martha Q Lacy
This phase I/II trial evaluated the maximum tolerated doses (MTD), safety and efficacy of pomalidomide, bortezomib and dexamethasone (PVD) combination in patients with relapsed, lenalidomide refractory, MM. In the phase I, dose level 1 consisted of pomalidomide 4mg PO days 1-21, bortezomib 1.0 mg/m(2) IV or SQ days 1,8,15,22 and dexamethasone 40mg PO days 1,8,15,22 given every 28 days. Bortezomib was increased to 1.3 mg/m(2) for dose level 2 and adopted in the phase 2 expansion cohort. We describe the results of 50 patients...
July 6, 2017: Blood
https://www.readbyqxmd.com/read/28683766/randomized-double-blind-placebo-controlled-phase-iii-study-of-ixazomib-plus-lenalidomide-dexamethasone-in-patients-with-relapsed-refractory-multiple-myeloma-china-continuation-study
#8
Jian Hou, Jie Jin, Yan Xu, Depei Wu, Xiaoyan Ke, Daobin Zhou, Jin Lu, Xin Du, Xiequn Chen, Junmin Li, Jing Liu, Neeraj Gupta, Michael J Hanley, Hongmei Li, Zhaowei Hua, Bingxia Wang, Xiaoquan Zhang, Hui Wang, Helgi van de Velde, Paul G Richardson, Philippe Moreau
BACKGROUND: The China Continuation study was a separate regional expansion of the global, double-blind, placebo-controlled, randomized phase III TOURMALINE-MM1 study of ixazomib plus lenalidomide-dexamethasone (Rd) in patients with relapsed/refractory multiple myeloma (RRMM) following one to three prior therapies. METHODS: Patients were randomized (1:1) to receive ixazomib 4.0 mg or placebo on days 1, 8, and 15, plus lenalidomide 25 mg on days 1-21 and dexamethasone 40 mg on days 1, 8, 15, and 22, in 28-day cycles...
July 6, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28679737/how-i-treat-first-relapse-of-myeloma
#9
Jean Luc Harousseau, Michel Attal
The standard treatment of relapsed multiple myeloma (MM) was either lenalidomide-dexamethasone (RD) or bortezomib-dexamethasone (VD) but it is changing rapidly for two reasons. Firstly lenalidomide and bortezomib are currently used in frontline treatment and many patients become resistant to these agents early in the course of their disease. Secondly six second-line new agents have been recently developed and offer new possibilities (pomalidomide, carfilzomib and ixazomib, panobinostat, elotuzumab and daratumumab)...
July 5, 2017: Blood
https://www.readbyqxmd.com/read/28677826/elotuzumab-plus-lenalidomide-dexamethasone-for-relapsed-or-refractory-multiple-myeloma-eloquent-2-follow-up-and-post-hoc-analyses-on-progression-free-survival-and-tumour-growth
#10
Meletios A Dimopoulos, Sagar Lonial, Darrell White, Philippe Moreau, Antonio Palumbo, Jesus San-Miguel, Ofer Shpilberg, Kenneth Anderson, Sebastian Grosicki, Ivan Spicka, Adam Walter-Croneck, Hila Magen, Maria-Victoria Mateos, Andrew Belch, Donna Reece, Meral Beksac, Eric Bleickardt, Valerie Poulart, Jennifer Sheng, Oumar Sy, Jessica Katz, Anil Singhal, Paul Richardson
The randomized phase III ELOQUENT-2 study (NCT01239797) evaluated the efficacy and safety of elotuzumab + lenalidomide/dexamethasone (ELd) versus lenalidomide/dexamethasone (Ld) in relapsed/refractory multiple myeloma. ELd reduced the risk of disease progression/death by 30% versus Ld (hazard ratio [HR] 0·70). Median time from diagnosis was 3·5 years. We present extended 3-year follow-up data. Endpoints included progression-free survival (PFS), overall response rate (ORR) and interim overall survival (OS)...
July 5, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28676669/carfilzomib-resistance-due-to-abcb1-mdr1-overexpression-is-overcome-by-nelfinavir-and-lopinavir-in-multiple-myeloma
#11
A Besse, S C Stolze, L Rasche, N Weinhold, G J Morgan, M Kraus, J Bader, H S Overkleeft, L Besse, C Driessen
Proteasome inhibitor carfilzomib has activity superior to bortezomib and is increasingly incorporated in multiple myeloma (MM) frontline therapy and relapsed settings. Most MM patients ultimately experience proteasome inhibitor-refractory disease, an unmet medical need with poorly understood biology and dismal outcome. Pharmacologic targeting of ABCB1 improved patient outcomes, including MM, but suffered from adverse drug effects and insufficient plasma concentrations. Proteomics analysis identified ABCB1 overexpression as the most significant change in carfilzomib-resistant MM cells...
July 5, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28669490/ilf2-is-a-regulator-of-rna-splicing-and-dna-damage-response-in-1q21-amplified-multiple-myeloma
#12
Matteo Marchesini, Yamini Ogoti, Elena Fiorini, Anil Aktas Samur, Luigi Nezi, Marianna D'Anca, Paola Storti, Mehmet Kemal Samur, Irene Ganan-Gomez, Maria Teresa Fulciniti, Nipun Mistry, Shan Jiang, Naran Bao, Valentina Marchica, Antonino Neri, Carlos Bueso-Ramos, Chang-Jiun Wu, Li Zhang, Han Liang, Xinxin Peng, Nicola Giuliani, Giulio Draetta, Karen Clise-Dwyer, Hagop Kantarjian, Nikhil Munshi, Robert Orlowski, Guillermo Garcia-Manero, Ronald A DePinho, Simona Colla
Amplification of 1q21 occurs in approximately 30% of de novo and 70% of relapsed multiple myeloma (MM) and is correlated with disease progression and drug resistance. Here, we provide evidence that the 1q21 amplification-driven overexpression of ILF2 in MM promotes tolerance of genomic instability and drives resistance to DNA-damaging agents. Mechanistically, elevated ILF2 expression exerts resistance to genotoxic agents by modulating YB-1 nuclear localization and interaction with the splicing factor U2AF65, which promotes mRNA processing and the stabilization of transcripts involved in homologous recombination in response to DNA damage...
July 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28668840/in-vitro-apoptosis-induction-by-fenofibrate-in-lymphoma-and-multiple-myeloma
#13
Leonard Christopher Schmeel, Frederic Carsten Schmeel, Ingo G H Schmidt-Wolf
BACKGROUND/AIM: Recent innovations in the treatment of multiple myeloma have enriched our therapeutic repertoire regarding the treatment of multiple myeloma during the last decades. However, despite today's therapies many multiple myeloma (MM) patients experience relapse of disease and eventually remain incurable. Wnt/β-catenin signaling has been demonstrated in lymphoma and MM, rendering related signaling molecules promising therapeutic targets. Fenofibrate, an extensively scrutinized and widely used drug for primary hypercholesterolemia or mixed dyslipidemia, has proven anticarcinogenic properties mediated by peroxisome proliferator-activated receptor-alpha (PPARα) agonism, thereby also influencing WNT-associated signaling molecules...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28661711/safety-of-ixazomib-for-the-treatment-of-multiple-myeloma
#14
Antoine Bonnet, Philippe Moreau
Despite a major positive impact of proteasome inhibitors (PI), such as bortezomib and carfilzomib, on the survival of patients with multiple myeloma (MM) over the last few years, their use in clinical practice is limited by the development of drug resistance, significant side-effects or constraining administration schedules. Ixazomib is the first, and for now the only, oral PI, which was approved by the US Food and Drug Administration in 2015 and by the European Medicines Agency in 2016. Areas covered: In this review, we provide an overview of the preclinical and early-phase studies of ixazomib used as single-agent and in combination...
July 12, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28660423/ixazomib-a-review-in-relapsed-and-or-refractory-multiple-myeloma
#15
REVIEW
Zaina T Al-Salama, Karly P Garnock-Jones, Lesley J Scott
The oral proteasome inhibitor ixazomib (Ninlaro(®)) is approved in the USA, EU and Japan in combination with lenalidomide and dexamethasone, for the treatment of patients with multiple myeloma (MM) who have received at least one prior therapy. In adults with relapsed and/or refractory MM who had received one to three prior therapies, progression-free survival (PFS) was significantly prolonged in patients who received the ixazomib- versus placebo-based triple therapy in the pivotal, global TOURMALINE-MM1 trial and its regional expansion (China continuation study)...
June 28, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28655599/final-results-of-a-phase-1-study-of-vorinostat-pegylated-liposomal-doxorubicin-and-bortezomib-in-relapsed-or-refractory-multiple-myeloma
#16
Peter M Voorhees, Cristina Gasparetto, Dominic T Moore, Diane Winans, Robert Z Orlowski, David D Hurd
INTRODUCTION/BACKGROUND: Deacetylase inhibitors have synergistic activity in combination with proteasome inhibitors and anthracyclines in preclinical models of multiple myeloma (MM). We therefore evaluated the safety and efficacy of the deacetylase inhibitor vorinostat in combination with pegylated liposomal doxorubicin (PLD) and bortezomib in relapsed/refractory MM. PATIENTS AND METHODS: Thirty-two patients were treated with PLD and bortezomib in combination with escalating doses of vorinostat on days 4 to 11 or 1 to 14...
May 10, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28655091/-outcomes-of-lenalidomide-based-treatment-for-57-patients-of-relapsed-or-refractory-multiple-myeloma
#17
S H Deng, Y Xu, W W Sui, G An, X H Mao, Z J Li, D H Zou, L G Qiu
Objective: To investigate the clinical efficacy and safety of lenalidomide (Revlimid, R) -based chemotherapy in the treatment of relapsed/refractory multiple myeloma (MM) patients. Methods: 57 consecutively relapsed/refractory MM patients were retrospectively analyzed from June 2013 to February 2016. All the patients received lenalidomide-based chemotherapy. Results: ① 60.4% patients had international staging system (ISS) stage Ⅲ, 37.9% patients had revised international staging system (R-ISS) stage Ⅲ, and 53...
June 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28653099/meeting-report-of-the-6th-heidelberg-myeloma-workshop-current-status-and-developments-in-diagnosis-and-therapy-of-multiple-myeloma
#18
Maximilian Merz, Marc S Raab, Hartmut Goldschmidt, Jens Hillengass
PURPOSE: The 6th Heidelberg Myeloma Workshop was held on May 5th and 6th, 2017 in the lecture hall of the University Hospital Heidelberg. METHODS AND RESULTS: Main topics of the meeting were (1) biology and genomics of multiple myeloma, (2) diagnostics and prognostic factors, (3) role of immunotherapy in multiple myeloma, as well as (4) therapy of multiple myeloma-drugs and treatment strategies. CONCLUSION: The landscape for the treatment of newly diagnosed and relapsed disease has significantly changed since the last Heidelberg Myeloma Workshop in 2015...
June 26, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28647392/a-novel-dual-inhibitor-of-microtubule-and-bruton-s-tyrosine-kinase-inhibits-survival-of-multiple-myeloma-and-osteoclastogenesis
#19
Manoj K Pandey, Krishne Gowda, Shen-Shu Sung, Thomas Abraham, Tulin Budak-Alpdogan, Giampolo Talamo, Sinisa Dovat, Shantu Amin
Bruton's tyrosine kinase (BTK) regulates many vital signaling pathways and plays a critical role in cell proliferation, survival, migration, and resistance. Previously, we reported that a small molecule, KS99, is an inhibitor of tubulin polymerization. In the present study, we explored whether KS99 is a dual inhibitor of BTK and tubulin polymerization. Although it is known that BTK is required for clonogenic growth and resistance, and microtubules are essential for cancer cell growth, dual targeting of these two components has not been explored previously...
June 22, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28643017/safety-and-efficacy-of-daratumumab-in-japanese-patients-with-relapsed-or-refractory-multiple-myeloma-a-multicenter-phase-1-dose-escalation-study
#20
Shinsuke Iida, Kenshi Suzuki, Shigeru Kusumoto, Masaki Ri, Nobuhiro Tsukada, Yu Abe, Masayuki Aoki, Mitsuo Inagaki
Safety, efficacy, and pharmacokinetics (PK) of daratumumab as a monotherapy were investigated in Japanese patients with relapsed/refractory multiple myeloma (MM). This multicenter, dose-escalation study included patients (age ≥20 years) with ≥2 prior therapies. Daratumumab was administered intravenously: 8 mg/kg (n = 4) and 16 mg/kg (n = 5). The primary endpoint was safety. Secondary endpoints included objective response, overall response rate (ORR), progression-free survival (PFS), PK, and immunogenicity...
June 22, 2017: International Journal of Hematology
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