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relapsed multiple myeloma

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https://www.readbyqxmd.com/read/28430175/carfilzomib-lenalidomide-dexamethasone-vs-lenalidomide-dexamethasone-in-relapsed-multiple-myeloma-by-previous-treatment
#1
M A Dimopoulos, A K Stewart, T Masszi, I Špička, A Oriol, R Hájek, L Rosiñol, D Siegel, G G Mihaylov, V Goranova-Marinova, P Rajnics, A Suvorov, R Niesvizky, A Jakubowiak, J San-Miguel, H Ludwig, S Ro, S Aggarwal, P Moreau, A Palumbo
Carfilzomib, a proteasome inhibitor, is approved as monotherapy and in combination with dexamethasone or lenalidomide-dexamethasone (Rd) for relapsed or refractory multiple myeloma. The approval of carfilzomib-lenalidomide-dexamethasone (KRd) was based on results from the randomized, phase 3 study ASPIRE (NCT01080391), which showed KRd significantly improved progression-free survival (PFS) vs Rd (median 26.3 vs 17.6 months; hazard ratio (HR)=0.690; P=0.0001). This subgroup analysis of ASPIRE evaluated KRd vs Rd by number of previous lines of therapy and previous exposure to bortezomib, thalidomide or lenalidomide...
April 21, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28427514/triplet-versus-doublet-combination-regimens-for-the-treatment-of-relapsed-or-refractory-multiple-myeloma-a-meta-analysis-of-phase-iii-randomized-controlled-trials
#2
REVIEW
Zhiqiang Sun, Fang Zheng, Suwan Wu, Yanjuan Liu, Hehe Guo, Yichen Liu
During the past decades, several prospective trials had been conducted to assess the efficacy and toxicities of triplet versus doublet combination regimens for the treatment of relapsed or refractory multiple myeloma (RRMM), but the results were controversial. We thus performed a systematic literature search to identify relevant trials. Summary hazard ratios (HRs), relative risks (RRs), and 95% confidence intervals (95%CIs) were calculated. A total of 3197 RRMM patients were included for analysis. The pooled results demonstrated that triplet combination therapies significantly improve OS (HR 0...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28427158/the-varied-distribution-and-impact-of-ras-codon-and-other-key-dna-alterations-across-the-translocation-cyclin-d-subgroups-in-multiple-myeloma
#3
Caleb K Stein, Charlotte Pawlyn, Shweta Chavan, Leo Rasche, Niels Weinhold, Adam Corken, Amy Buros, Pieter Sonneveld, Graham H Jackson, Ola Landgren, Tariq Mughal, Jie He, Bart Barlogie, P Leif Bergsagel, Faith E Davies, Brian A Walker, Gareth J Morgan
We examined a set of 805 cases that underwent DNA sequencing using the FoundationOne Heme (F1H) targeted sequencing panel and gene expression profiling. Known and likely variant calls from the mutational data were analyzed for significant associations with gene expression defined translocation cyclin D (TC) molecular subgroups. The spectrum of KRAS, NRAS, and BRAF codon mutations varied across subgroups with NRAS mutations at Q61 codon being common in hyperdiploid (HRD) and t(11;14) myeloma while being rare in MMSET and MAF...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28425720/a-cereblon-modulator-cc-220-with-improved-degradation-of-ikaros-and-aiolos
#4
Mary E Matyskiela, Weihong Zhang, Hon-Wah Man, George Muller, Godrej Khambatta, Frans Baculi, Matthew Hickman, Laurie LeBrun, Barbra Pagarigan, Gilles Carmel, Chin-Chun Lu, Gang Lu, Mariko Riley, Yoshitaka Satoh, Peter Schafer, Thomas O Daniel, James Carmichael, Brian E Cathers, Philip P Chamberlain
The drugs lenalidomide and pomalidomide bind to the protein cereblon, directing the CRL4-CRBN E3 ligase toward the transcription factors Ikaros and Aiolos to cause their ubiquitination and degradation. Here we describe CC-220 (compound 6), a cereblon modulator in clinical development for systemic lupus erythematosis and relapsed/refractory multiple myeloma. Compound 6 binds cereblon with a higher affinity than lenalidomide or pomalidomide. Consistent with this, the cellular degradation of Ikaros and Aiolos is more potent and the extent of substrate depletion is greater...
April 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28424963/pharmacokinetics-and-safety-of-carfilzomib-in-patients-with-relapsed-multiple-myeloma-and-end-stage-renal-disease-esrd-an-open-label-single-arm-phase-i-study
#5
Hang Quach, Darrell White, Andrew Spencer, P Joy Ho, Divaya Bhutani, Mike White, Sandeep Inamdar, Chris Morris, Ying Ou, Martin Gyger
PURPOSE: The pharmacokinetics (PK) of carfilzomib have been previously studied in multiple myeloma patients with varying degrees of renal impairment (normal, mild, moderate, severe, and end-stage renal disease [ESRD]) at doses of 15 and 20 mg/m(2). This study evaluated carfilzomib PK at higher doses of 27 and 56 mg/m(2) in normal renal function and ESRD patients. METHODS: Patients received carfilzomib on two consecutive days/week for 3 weeks every 28-day cycle: 20 mg/m(2) (cycle 1 day 1-2), escalated to 27 mg/m(2) on cycle 1 day 8; if tolerated, 56 mg/m(2) starting cycle 2 day 1...
April 19, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28423741/lenalidomide-and-the-risk-of-serious-infection-in-patients-with-multiple-myeloma-a-systematic-review-and-meta-analysis
#6
Li Ying, Tong YinHui, Zheng Yunliang, Haozhen Sun
The immunomodulatory drug lenalidomide is highly effective against newly diagnosed and relapsed/refractory multiple myeloma (MM), but serious and even fatal infections have been associated with its use. In this meta-analysis, we assessed the overall risk of infection to MM patients treated with lenalidomide. Eleven phase II or III clinical trials, comprising 3,210 subjects, were selected from the Embase, Pubmed, and Cochrane Library databases, from the Clinical Trial Registration website, and from meeting abstracts and virtual presentations at the American Society of Clinical Oncology...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28409228/diagnosis-and-treatment-of-multiple-myeloma-in-germany-analysis-of-a-nationwide-multi-institutional-survey
#7
Maximilian Merz, Lenka Kellermann, Wolfram Poenisch, Hans-Joachim Tischler, Joern Kohnke, Wolfgang Knauf, Hartmut Goldschmidt
A nationwide, multi-institutional survey was performed in 2011 and 2015 to analyze routine practice for myeloma patients outside clinical trials in Germany. We contacted university hospitals, community hospitals, and office-based hematologists in order to enter clinical data from newly diagnosed and relapsed patients into an online platform. Complete datasets were available for 478 (2011) and 515 (2015) patients. While median age at diagnosis increased from 70 to 72 years, patients had fewer concomitant diseases (2011 61%; 2015 51%) and presented with equal performance status (ECOG 0-1, 2011 66%; 2015 68%)...
April 13, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28402163/bortezomib-melphalan-and-prednisone-in-elderly-relapsed-refractory-multiple-myeloma-patients-update-of-multicenter-open-label-phase-1-2-study
#8
Sara Grammatico, Sara Bringhen, Federico Vozella, Agostina Siniscalchi, Mario Boccadoro, Maria Teresa Petrucci
No abstract text is available yet for this article.
April 12, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28400475/an-ex-vivo-platform-for-the-prediction-of-clinical-response-in-multiple-myeloma
#9
Ariosto S Silva, Maria D Silva, Praneeth Sudalagunta, Allison I Distler, Timothy Jacobson, Aunshka Collins, Tuan Nguyen, Jinming Song, Dung-Tsa Chen, Lu Chen, Christopher L Cubitt, Rachid Baz, Lia Perez, Dmitri Rebatchouk, William Dalton, James Greene, Robert A Gatenby, Robert J Gillies, Eduardo Sontag, Mark B Meads, Kenneth Shain
Multiple myeloma (MM) remains treatable but incurable. Despite a growing armamentarium of effective agents, choice of therapy, especially in relapse, still relies almost exclusively on clinical acumen. We have developed a system, EMMA (Ex vivo Mathematical Myeloma Advisor), consisting of patient-specific mathematical models parameterized by an ex vivo assay that reverse engineers the intensity and heterogeneity of chemosensitivity of primary cells from MM patients, allowing us to predict clinical response to up to 31 drugs within 5 days post-bone marrow biopsy...
April 11, 2017: Cancer Research
https://www.readbyqxmd.com/read/28393375/long-term-outcome-of-patients-with-solitary-plasmacytoma-treated-with-radiotherapy-a-population-based-single-center-study-with-median-follow-up-of-13-7%C3%A2-years
#10
Dlawer Abdulla Barzenje, Arne Kolstad, Waleed Ghanima, Harald Holte
In this single-center, population-based, and retrospective study, we analyzed the outcome of 49 patients with solitary bone plasmacytoma (SBP) and 28 patients with solitary extramedullary plasmacytoma (SEP), all treated with radiotherapy. Laminectomy was performed in 18/30 SBP patients with vertebral involvement and tumour resection in 10 SEP patients. Overall survival and cause of death for each patient were compared to 5 sex-, age-, and residency-matched individuals from the normal population. Response (complete and partial) was achieved in 94% of SBP and 96% of SEP patients...
April 9, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28390534/pet-mr-imaging-of-multiple-myeloma
#11
REVIEW
Shetal N Shah, Jorge D Oldan
PET-magnetic resonance (MR) is a hybrid imaging modality that combines PET and MR. Evidence for this new modality is in the process of being developed, but both component modalities are well tested in the diagnosis and management of multiple myeloma. It allows advanced bimodality imaging of the whole body with an adaptable field of view and it can be used for monitoring plasma cell dyscrasias for progression to multiple myeloma, for assessing disease burden in patients with known multiple myeloma, for assessing response to therapy and relapse after remission, and for radiation therapy treatment planning...
May 2017: Magnetic Resonance Imaging Clinics of North America
https://www.readbyqxmd.com/read/28388253/lenalidomide-in-the-treatment-of-chronic-lymphocytic-leukemia
#12
Gilad Itchaki, Jennifer R Brown
Lenalidomide is an immunomodulatory drug (IMiD) with a unique mode of action (MOA) that may vary across disease-type. It is currently approved in multiple myeloma (MM), myelodysplastic syndrome (MDS) and mantle cell lymphoma (MCL), yet is also clinically active in a host of lymphoproliferative diseases, including chronic lymphocytic leukemia (CLL). Due to its protean effects on the immune system, lenalidomide may be particularly appealing in CLL, which is distinct in its ability to evade immune recognition and cause immunosuppression...
April 7, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28388244/which-therapies-will-move-to-the-front-line-for-multiple-myeloma
#13
María J Cejalvo, Javier de la Rubia
Despite substantial progress, multiple myeloma (MM) remains an incurable disease. Recently the availability of several novel drugs with different and innovative mechanisms of action (daratumumab, elotuzumab, carfilzomib, ixazomib, and panobinostat) has increased the therapeutic options but has also increased complexity in the management of patients with MM. Areas covered: The outstanding results observed in the relapsed setting with regimens including these new drugs has provided the investigators with several treatment options that are being tested also in patients with newly diagnosed MM...
April 7, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28387460/marizomib-for-central-nervous-system-multiple-myeloma
#14
Ashraf Badros, Zeba Singh, Binod Dhakal, Young Kwok, Ann MacLaren, Paul Richardson, Mohit Trikha, Parameswaran Hari
Marizomib, a natural marine product, is an irreversible proteasome inhibitor currently under investigation in relapsed-refractory multiple myeloma (RRMM) and malignant glioma. Central nervous system-multiple myeloma (CNS-MM) is a rare manifestation of extra-medullary disease with few therapeutic options, highlighting the unmet clinical need in these patients. Marizomib demonstrated encouraging activity in RRMM and has emerging clinical activity in glioma, making it a potential CNS-MM therapeutic intervention...
April 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28385781/monitoring-of-multiple-myeloma-by-quantification-of-recurrent-mutations-in-serum
#15
Even Holth Rustad, Eivind Coward, Emilie R Skytøen, Kristine Misund, Toril Holien, Therese Standal, Magne Børset, Vidar Beisvag, Ola Myklebost, Leonardo A Meza-Zepeda, Hong Yan Dai, Anders Sundan, Anders Waage
Circulating tumor DNA (ctDNA) is a promising biomarker to monitor tumor load and genome alterations. We have explored the presence of ctDNA in multiple myeloma patients and its relation to disease activity during long-term follow-up. We used digital droplet PCR to monitor recurrent mutations, mainly in mitogen activated protein kinase pathway genes NRAS, KRAS and BRAF. Mutations were identified by next generation sequencing or PCR of bone marrow plasma cells, and their presence analyzed in 251 archived serum samples obtained from 20 patients during up to 7 years...
April 6, 2017: Haematologica
https://www.readbyqxmd.com/read/28385778/double-autophagy-stimulation-using-chemotherapy-and-mtor-inhibition-combined-with-hydroxychloroquine-for-autophagy-modulation-in-patients-with-relapsed-or-refractory-multiple-myeloma
#16
Emma C Scott, Richard T Maziarz, Stephen E Spurgeon, Eva Medvedova, James Gajewski, Shara Reasor-Heard, Byung Park, Anne Kratz, George V Thomas, Marc Loriaux, Michael Cascio, Jennifer Podolak, Miranda Gordon, Jennifer Botelho, Edward Stadtmauer, Ravi Amaravadi, Dan T Vogl
No abstract text is available yet for this article.
April 6, 2017: Haematologica
https://www.readbyqxmd.com/read/28370401/cyclophosphamide-based-stem-cell-mobilization-in-relapsed-multiple-myeloma-patients-a-subgroup-analysis-from-the-phase-iii-trial-relapse
#17
Marc-Andrea Baertsch, Jana Schlenzka, Katharina Lisenko, Julia Krzykalla, Natalia Becker, Katja Weisel, Richard Noppeney, Hans Martin, Hans W Lindemann, Mathias Haenel, Axel Nogai, Christof Scheid, Hans Salwender, Roland Fenk, Ullrich Graeven, Peter Reimer, Martin Schmidt-Hieber, Martin Goerner, Ingo G H Schmidt-Wolf, Stefan Klein, Anthony D Ho, Hartmut Goldschmidt, Patrick Wuchter
OBJECTIVE: Analysis of the efficiency and toxicity of cyclophosphamide based stem cell mobilization in patients with relapsed mulitple myeloma (RMM). METHODS: Peripheral blood stem cells were mobilized with high dose cyclophosphamide (2 g /m(2) daily on days 1 and 2) and G-CSF plus pre-emptive/rescue plerixafor in RMM patients (1(st) to 3(rd) relapse) treated within the ReLApsE trial of the German-Speaking Myeloma Multicenter Group (GMMG). RESULTS: Mobilization was initiated with high dose cyclophosphamide and G-CSF in 30 patients...
March 31, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28368259/role-of-18-f-fdg-pet-ct-in-the-diagnosis-and-management-of-multiple-myeloma-and-other-plasma-cell-disorders-a-consensus-statement-by-the-international-myeloma-working-group
#18
REVIEW
Michele Cavo, Evangelos Terpos, Cristina Nanni, Philippe Moreau, Suzanne Lentzsch, Sonja Zweegman, Jens Hillengass, Monika Engelhardt, Saad Z Usmani, David H Vesole, Jesus San-Miguel, Shaji K Kumar, Paul G Richardson, Joseph R Mikhael, Fernando Leal da Costa, Meletios-Athanassios Dimopoulos, Chiara Zingaretti, Niels Abildgaard, Hartmut Goldschmidt, Robert Z Orlowski, Wee Joo Chng, Hermann Einsele, Sagar Lonial, Bart Barlogie, Kenneth C Anderson, S Vincent Rajkumar, Brian G M Durie, Elena Zamagni
The International Myeloma Working Group consensus aimed to provide recommendations for the optimal use of (18)fluorodeoxyglucose ((18)F-FDG) PET/CT in patients with multiple myeloma and other plasma cell disorders, including smouldering multiple myeloma and solitary plasmacytoma. (18)F-FDG PET/CT can be considered a valuable tool for the work-up of patients with both newly diagnosed and relapsed or refractory multiple myeloma because it assesses bone damage with relatively high sensitivity and specificity, and detects extramedullary sites of proliferating clonal plasma cells while providing important prognostic information...
April 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28367342/remission-of-severe-relapsed-and-refractory-ttp-after-multiple-cycles-of-bortezomib
#19
Manu R Pandey, Pankit Vachhani, Evelena P Ontiveros
Acquired thrombotic thrombocytopenic purpura (TTP) is characterized by autoantibodies against a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13). Uncleaved von Willebrand factor (VWF) multimers accumulate and bind to platelets which causes spontaneous microthrombi ultimately causing microangiopathic hemolytic anemia, thrombocytopenia, and end-organ ischemia. Plasma exchange (PEX) with or without steroids constitutes standard first-line therapy with rituximab typically reserved for refractory cases...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28360146/resistin-induces-multidrug-resistance-in-myeloma-by-inhibiting-cell-death-and-upregulating-abc-transporter-expression
#20
Jianan Pang, Qiaofa Shi, Zhiqiang Liu, Jin He, Huan Liu, Pei Lin, Jiuwei Cui, Jing Yang
Despite advances in therapy, multiple myeloma remains incurable, with a high frequency of relapse. This suggests the need to identify additional factors that contribute to drug resistance. Our previous studies revealed that bone marrow adipocytes promote chemotherapy resistance in myeloma through adipocyte-secreted adipokines, but the mechanism underlying this effect and the specific adipokines involved are not well understood. We proposed to determine the role of resistin, an adipokine which is secreted from adipocytes, in myeloma chemotherapy resistance...
March 30, 2017: Haematologica
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