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https://www.readbyqxmd.com/read/29054949/metachronous-solitary-plasmacytoma
#1
Robin Khosa, Shishir Seth, Sapna Nangia
Solitary plasmacytoma is a rare disorder comprising 5%-10% of all plasma cell neoplasms. Progression to multiple myeloma is the most common pattern of relapse. Appearance of new lesions without any systemic disease is the most unusual pattern of relapse seen in <2% cases. We present a case of a 46-year-old female who presented with features of third and seventh cranial nerve palsy, diagnosed with solitary plasmacytoma, with no evidence of any systemic disease. As per standard recommendations, the patient received radiotherapy to the local site...
October 19, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/29054911/ixazomib-significantly-prolongs-progression-free-survival-in-high-risk-relapsed-refractory-myeloma-patients
#2
Hervé Avet-Loiseau, Nizar J Bahlis, Wee-Joo Chng, Tamas Masszi, Luisa Viterbo, Ludek Pour, Peter Ganly, Antonio Palumbo, Michele Cavo, Christian Langer, Andrzej Pluta, Arnon Nagler, Shaji Kumar, Dina Ben-Yehuda, S Vincent Rajkumar, Jesus San-Miguel, Deborah Berg, Jianchang Lin, Helgi van de Velde, Dixie-Lee Esseltine, Alessandra di Bacco, Philippe Moreau, Paul G Richardson
Certain cytogenetic abnormalities are known to adversely impact outcomes in patients with multiple myeloma (MM). The phase 3 TOURMALINE-MM1 study demonstrated a significant improvement in progression-free survival (PFS) with ixazomib-lenalidomide-dexamethasone (IRd) compared with placebo-Rd. This pre-planned analysis assessed the efficacy and safety of IRd versus placebo-Rd according to cytogenetic risk, as assessed using fluorescence in-situ hybridization. High-risk cytogenetic abnormalities were defined as del(17p), t(4;14), and/or t(14;16); additionally, patients were assessed for 1q21 amplification...
October 20, 2017: Blood
https://www.readbyqxmd.com/read/29054515/blood-transfusion-management-and-transfusion-related-outcomes-in-daratumumab-treated-patients-with-relapsed-or-refractory-multiple-myeloma
#3
Ajai Chari, Suzanne Arinsburg, Sundar Jagannath, Toshihisa Satta, Ivey Treadwell, Donna Catamero, Gillian Morgan, Huaibao Feng, Clarissa Uhlar, Imran Khan, Parul Doshi, Saad Usmani
INTRODUCTION: Daratumumab, a human CD38 monoclonal antibody approved for multiple myeloma (MM) treatment, binds red blood cells (RBCs), resulting in panagglutination in compatibility tests. Published mitigation methods avoid additional testing, ensuring timely release of blood products. Blood transfusion management and transfusion-related outcomes of daratumumab-treated patients in the SIRIUS study are reported, with emphasis on 2 clinical sites. PATIENTS AND METHODS: Patients had MM treated with ≥ 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug, or were refractory to a proteasome inhibitor and an immunomodulatory drug...
September 19, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29052093/emerging-small-molecule-approaches-to-enhance-the-antimyeloma-benefit-of-proteasome-inhibitors
#4
James J Driscoll, Magen Brailey
Multiple myeloma (MM) is a clonal plasma cell malignancy which, despite recent treatment advances, remains incurable in the vast majority of the over 118,000 patients in the USA afflicted with this disease. Treatment of MM has dramatically improved in the past decade with the introduction of new drugs into therapeutic strategies in both the frontline and relapse settings that has led to a significant improvement in the median overall survival (OS). These drugs have been incorporated into clinical guidelines and transformed the treatment approach to MM...
October 19, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/29045072/cell-signaling-model-connects-vorinostat-pharmacokinetics-and-tumor-growth-response-in-multiple-myeloma-xenografts
#5
Charvi Nanavati, Donna Ruszaj, Donald E Mager
Multiple myeloma is a fatal hematological malignancy with high rates of drug resistance and relapse. Vorinostat, a histone deacetylase inhibitor, has shown promise in enhancing efficacy when combined with current myeloma therapies. In this study, temporal changes of critical proteins and cell proliferation were measured in myeloma cells exposed to vorinostat. A model linking biomarker dynamics to cell proliferation was developed that captured vorinostat effects on signal transduction and cell viability. The model structure and parameters were fixed to describe tumor dynamics in vivo, and tumor-specific growth and death rate parameters were estimated...
October 17, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/29032267/long-term-follow-up-of-a-donor-versus-no-donor-comparison-in-multiple-myeloma-patients-at-first-relapse-after-failing-autologous-transplantation
#6
Francesca Patriarca, Benedetto Bruno, Hermann Einsele, Francesco Spina, Luisa Giaccone, Vittorio Montefusco, Miriam Isola, Chiara Nozzoli, Andrea Nozza, Fortunato Morabito, Paolo Corradini, Renato Fanin
We report the long-term clinical outcomes of a retrospective multicentre study that enrolled 169 multiple myeloma (MM) patients at first relapse after failing autologous stem cell transplantation (SCT). After HLA-typing at relapse, 79 patients with a suitable donor, 72 (91%) of whom eventually underwent salvage allogeneic SCT, were compared with 90 patients without a donor who were treated with multiple lines of salvage treatment with bortezomib and/or immune-modulating agents. At a median follow-up of 30 months (range 2-180) for all patients and 110 months (range 38-180) for surviving patients, 7-year progression free survival (PFS) was 18% in the donor group and 0% in the no-donor group (hazard ratio [HR] 2...
October 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29030084/characterization-and-use-of-the-novel-human-multiple-myeloma-cell-line-mc-b11-14-to-study-biological-consequences-of-crispr-mediated-loss-of-immunoglobulin-a-heavy-chain
#7
Denise K Walters, Bonnie K Arendt, Renee C Tschumper, Xiaosheng Wu, Diane F Jelinek
The genetic abnormalities underlying multiple myeloma (MM) are notoriously complex and intraclonal heterogeneity is a common disease feature. In the current study, we describe the establishment of a monoclonal IgA kappa (κ) MM cell line, designated MC-B11/14. Cytogenetic and FISH analyses of the original and relapse patient samples revealed the MM clone was non-hyperdiploid and possessed an 11;14 chromosomal translocation. The MC-B11/14 cell line, established from the relapse sample, is tetraploid and houses the t(11;14) abnormality...
October 10, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/29027825/cost-effectiveness-of-carfilzomib-plus-dexamethasone-compared-with-bortezomib-plus-dexamethasone-for-patients-with-relapsed-or-refractory-multiple-myeloma-in-the-united-states
#8
Andrzej J Jakubowiak, Ivan Houisse, István Májer, Ágnes Benedict, Marco Campioni, Sumeet Panjabi, Sikander Ailawadhi
BACKGROUND: We assessed the economic value of carfilzomib 56 mg/m(2) and dexamethasone (Kd56) vs bortezomib and dexamethasone (Vd) for relapsed/refractory multiple myeloma (R/RMM) using ENDEAVOR trial results. RESEARCH DESIGN AND METHODS: Cost-effectiveness of Kd56 vs Vd was assessed using a partitioned survival model by estimating progression-free survival, overall survival, and direct costs over a lifetime horizon. Surveillance Epidemiology and End Results (SEER) survival data were extrapolated after matching registry and ENDEAVOR patients...
October 13, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/29026685/pharmacokinetics-of-carfilzomib-in-patients-with-advanced-malignancies-and-varying-degrees-of-hepatic-impairment-an-open-label-single-arm-phase-1-study
#9
Jennifer Brown, Ruth Plummer, Todd M Bauer, Stephen Anthony, John Sarantopoulos, Filip De Vos, Mike White, Marco Schupp, Ying Ou, Ulka Vaishampayan
BACKGROUND: Carfilzomib is approved in the United States and Europe for treatment of relapsed or refractory multiple myeloma (MM). This study evaluated pharmacokinetics (PK) and safety of carfilzomib in patients with relapsed or progressive advanced malignancies and varying degrees of impaired hepatic function. METHODS: Patients with normal hepatic function (normal) or hepatic impairment (mild, moderate, or severe) received carfilzomib infusion in 28-day cycles...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29018077/efficacy-of-venetoclax-as-targeted-therapy-for-relapsed-refractory-t-11-14-multiple-myeloma
#10
Shaji Kumar, Jonathan L Kaufman, Cristina Gasparetto, Joseph Mikhael, Ravi Vij, Brigitte Pegourie, Lofti Benboubker, Thierry Facon, Martine Amiot, Philippe Moreau, Elizabeth A Punnoose, Stefanie Alzate, Martin Dunbar, Tu Xu, Suresh K Agarwal, Sari Heitner Enschede, Joel D Leverson, Jeremy A Ross, Paulo C Maciag, Maria Verdugo, Cyrille Touzeau
Venetoclax is a selective, orally bioavailable BCL-2 inhibitor that induces cell death in MM cells, particularly in those harboring t(11;14), which express high levels of BCL-2 relative to BCL-XL and MCL-1. In this phase I study, patients with relapsed/refractory MM received venetoclax monotherapy. After a 2-week lead-in with weekly dose escalation, daily venetoclax was given at 300, 600, 900, or 1200 mg in dose-escalation cohorts and 1200 mg in the safety expansion. Dexamethasone could be added upon progression during treatment...
October 10, 2017: Blood
https://www.readbyqxmd.com/read/28993177/dkk1-and-sclerostin-are-early-markers-of-relapse-in-multiple-myeloma
#11
Charlotte Mabille, Adeline Ruyssen Witrand, Yannick Degboe, Isabelle Gennero, Herve Avet Loiseau, Murielle Roussel, Benjamin Hebraud, Delphine Nigon, Michel Attal, Michel Laroche
Recent studies have shown that Dickkopf-related protein (DKK1) and sclerostin decrease when a complete response (CR) is obtained after chemotherapy in myeloma multiple (MM). To study variations in DKK1, sclerostin and P1NP in patients treated for MM, between complete response (CR) and relapse, we carried out a prospective study ancillary to the IFM 2009 protocol (IFM). The aim of IFM was to compare progression-free survival between patients treated with chemotherapy with or without transplantation. We selected 69 patients who reached CR and relapsed...
October 6, 2017: Bone
https://www.readbyqxmd.com/read/28987930/impact-of-new-drugs-on-the-long-term-follow-up-of-upfront-tandem-auto-allo-transplant-in-multiple-myeloma
#12
Luisa Giaccone, Andrea Evangelista, Francesca Patriarca, Roberto Sorasio, Massimo Pini, Fabrizio Carnevale-Schianca, Moreno Festuccia, Lucia Brunello, Francesco Zallio, Enrico Maffini, Paola Omedé, Sara Bringhen, Nicola Mordini, Renato Fanin, Giovannino Ciccone, Mario Boccadoro, Benedetto Bruno
Prior to the introduction of "new drugs", we designed a trial where 162 newly diagnosed myeloma patients were biologically randomized to receive either an autograft (auto-SCT) followed by a non-myeloablative allograft (allo-SCT) or a double auto-SCT. Fifty-eight patients in the allo-SCT arm and 46 in the double auto-SCT arm completed the assigned treatment. At median follow-up of 12.3 years from allo-SCT and 12.1 years from second auto-SCT, median overall survival (OS) was 11.4 in the allo-SCT arm and 3.9 years in the auto-SCT -arm (p=0...
October 4, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28983805/influence-of-disease-and-patient-characteristics-on-daratumumab-exposure-and-clinical-outcomes-in-relapsed-or-refractory-multiple-myeloma
#13
Xiaoyu Yan, Pamela L Clemens, Thomas Puchalski, Sagar Lonial, Henk Lokhorst, Peter M Voorhees, Saad Usmani, Paul G Richardson, Torben Plesner, Kevin Liu, Robert Z Orlowski, Nedjad Losic, Richard Jansson, Tahamtan Ahmadi, Kristen Lantz, Juan Jose Perez Ruixo, Honghui Zhou, Xu Steven Xu
OBJECTIVE: The aim of this study was to understand the influence of disease and patient characteristics on exposure to daratumumab, an immunoglobulin Gκ (IgGκ) monoclonal antibody, and clinical outcomes in relapsed or refractory multiple myeloma (MM). PATIENTS AND METHODS: Baseline myeloma type, albumin levels, renal/hepatic function, age, sex, race, weight, Eastern Cooperative Oncology Group (ECOG) status, refractory status, and number of prior therapies were evaluated using data from two clinical studies-GEN501 (N = 104) and SIRIUS (N = 124)...
October 5, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28978849/therapeutic-approach-for-relapsed-refractory-multiple-myeloma-the-logic-and-practice
#14
Junya Kuroda
The long-term outcome of multiple myeloma (MM) has been greatly improved by the advent of new agents such as proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs), despite the disease remaining mostly incurable. Treatment design is the critical determinant for the survival period and for the quality and way of life in patients with relapsed/refractory MM (RRMM). Recently, the choice of therapeutic options for RRMM has been expanded by the introduction of second generation PIs such as carfilzomib and ixazomib, and therapeutic monoclonal antibodies such as elotuzumab and daratumumab...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28977957/meta-analysis-of-the-efficacy-of-treatments-for-newly-diagnosed-and-relapsed-refractory-multiple-myeloma-with-del-17p
#15
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, I(2) = 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, I(2) = 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...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28967482/cost-effectiveness-of-pomalidomide-carfilzomib-and-daratumumab-for-the-treatment-of-patients-with-heavily-pretreated-relapsed-refractory-multiple-myeloma-in-the-united-states
#16
Christopher G Pelligra, Kejal Parikh, Shien Guo, Conor Chandler, Jorge Mouro, Safiya Abouzaid, Sikander Ailawadhi
PURPOSE: Pomalidomide plus low-dose dexamethasone (POM-d), daratumumab monotherapy (DARA), and carfilzomib monotherapy (CAR) have been approved for use in the treatment of patients with heavily pretreated relapsed-refractory multiple myeloma (RRMM) in the US, based on findings from the MM-002, SIRIUS, and PX-171-003-A1 studies, respectively. The objective of this study was to assess the cost-effectiveness of POM-d, DARA, and CAR in this patient population from a US payer's perspective...
September 26, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28966941/increased-expression-of-the-tight-junction-protein-tjp1-zo-1-is-associated-with-upregulation-of-taz-tead-activity-and-an-adult-tissue-stem-cell-signature-in-carfilzomib-resistant-multiple-myeloma-cells-and-high-risk-multiple-myeloma-patients
#17
Irene Riz, Robert G Hawley
Tight junction protein 1 (TJP1) has recently been proposed as a biomarker to identify multiple myeloma (MM) patients most likely to respond to bortezomib- and carfilzomib-based proteasome inhibitor regimens. Herein we report increased expression of TJP1 during the adaptive response mediating carfilzomib resistance in the LP-1/Cfz MM cell line. Moreover, increased TJP1 expression delineated a subset of relapsed/refractory MM patients on bortezomib-based therapy sharing an LP-1/Cfz-like phenotype characterized by activation of interacting transcriptional effectors of the Hippo signaling cascade (TAZ and TEAD1) and an adult tissue stem cell signature...
July 2017: Oncoscience
https://www.readbyqxmd.com/read/28963446/clinical-features-of-multiple-myeloma-patients-with-isolated-extramedullary-relapse
#18
Xiao-Yan Qu, Li-Juan Chen, Tian Tian, Li-Min Duan, Rui-Nan Lu, Hua Lu, Han-Xin Wu, Jian-Yong Li
This study sought to analyze the clinical features and prognosis of multiple myeloma with isolated extramedullary relapse and with the absence of systemic progression. The clinical features and outcome were retrospectively analyzed in six multiple myeloma patients. These patients had secretory multiple myeloma at diagnosis. When relapsed, the dissociation between medullary and extramedullary response was detected. The serum or urine monoclonal component was extremely low or absent. The plasma cells in bone marrow were<5%...
September 30, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28951562/a-compound-chimeric-antigen-receptor-strategy-for-targeting-multiple-myeloma
#19
K H Chen, M Wada, K G Pinz, H Liu, X Shuai, X Chen, L E Yan, J C Petrov, H Salman, L Senzel, E L H Leung, X Jiang, Y Ma
Current clinical outcomes using CARs against multiple myeloma show promise in the eradication of bulk disease. However, these anti-BCMA (CD269) CARs observe relapse as a common phenomenon after treatment due to the reemergence of either antigen positive or negative cells. Hence, the development of improvements in CAR design to target antigen loss and increase effector cell persistency represents a critical need. Here, we report on the anti-tumor activity of a CAR T-cell possessing 2 complete and independent CAR receptors against the multiple myeloma antigens BCMA and CS1...
September 27, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28948001/emerging-drugs-and-combinations-to-treat-multiple-myeloma
#20
REVIEW
Alessandra Larocca, Roberto Mina, Francesca Gay, Sara Bringhen, Mario Boccadoro
In the past few years, multiple targeted therapies and immunotherapies including second generation immunomodulatory drugs (pomalidomide) and proteasome inhibitors (carfilzomib, ixazomib), monoclonal antibodies and checkpoint inhibitors were approved for the treatment of myeloma or entered advanced phases of clinical testing. These agents showed significant activity in advanced myeloma and increased the available treatment strategies. Pomalidomide is well-tolerated and effective in patients with relapsed/refractory multiple myeloma who have exhausted any possible treatment with lenalidomide and bortezomib...
September 1, 2017: Oncotarget
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