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https://www.readbyqxmd.com/read/29667156/how-we-manage-patients-with-plasmacytomas
#1
REVIEW
Despina Fotiou, Meletios A Dimopoulos, Efstathios Kastritis
PURPOSE OF REVIEW: To discuss the diagnostic approach, treatment options, and future considerations in the management of plasmacytomas, either solitary or in the context of overt multiple myeloma (MM). RECENT FINDINGS: Advanced imaging techniques such as whole-body magnetic resonance imaging and positron emission tomography/computerized tomography are essential for the diagnostic workup of solitary plasmacytomas (SP) to rule out the presence of other disease foci...
April 17, 2018: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29665944/-current-status-and-challenges-of-car-t-immunotherapy-in-hematologic-malignancies-review
#2
Xin Cheng, Ya-Jie Wang, Shuai Feng, Ya-Yun Wu, Tong-Hua Yang, Xun Lai
The chimeric antigen receptor (CAR) T cell therapy has gradually became a new trend in the treatment of refractory and relapsed hematologic malignancies by developing for 30 years. With the exciting development of genetic engineering, CAR-T technology has subjected to 4 generations of innovation. Structure of CAR-T started from a single signal molecule to 2 or more than 2 co-stimulatory molecules, and then coding the CAR gene or promoter. CAR-T can specifically recognize tumor antigens, and does not be restricted by major histocompatibility complex (MHC), thus making a breakthrough in clinical treatment...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29665938/-research-and-applications-progress-of-lenalidomide-in-relapsed-refractory-blood-system-diseases-review
#3
Wen-Jing Fan, Zhi-Qiao Fan, Tao Wu, Hai Bai
Lenalidomide, a novel immunomodulatory agent, is a kind of thalidomide derivatives, which shows a good efficacy and safety for hematological system diseases. This review is aimed to evaluate the efficacy and safety of lenalidomide in treatment of patients with multiple myeloma, chronic lymphocytic leukemia, acute myeloid leukemia, non-Hodgkin's lymphoma, classical Hodgkin's lymphoma and POEMS syndrome at their replased or refractory state. At the same time, this review focuses on the newest clinical research and the latest application progress of lenalidomide for relapsed or refractory hematological system diseases...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29665144/disulfiram-copper-targets-stem-cell-like-aldh-population-of-multiple-myeloma-by-inhibition-of-aldh1a1-and-hedgehog-pathway
#4
Na Jin, Xiaojian Zhu, Fanjun Cheng, Liling Zhang
Multiple myeloma stem cells (MMSCs) have been considered as the major cause resulting in relapse. Eradicating MMSCs may be an effective strategy to improve the outcome of multiple myeloma (MM). Increased activity of aldehyde dehydrogenase (ALDH) has been found in MMSCs, but whether inhibiting ALDH activity can eliminate MMSCs remains unknown. Disulfiram (DS) has been reported as an inhibitor of ALDH, and increasing studies showed it has anti-cancer effects in a copper (Cu)-dependent manner. In this study, we isolated ALDH+ cells of MM by Aldefluor assay and demonstrated they possessed tumorigenesis capacities in vitro and in vivo...
April 17, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29656139/analysis-of-clinical-factors-and-outcomes-associated-with-non-utilization-of-collected-peripheral-blood-stem-cells-for-autologous-stem-cell-transplants-in-transplant-eligible-patients-with-multiple-myeloma
#5
Ankit Kansagra, Wilson I Gonsalves, Morie A Gertz, Francis K Buadi, David Dingli, Angela Dispenzieri, Martha Q Lacy, Suzanne R Hayman, Prashant Kapoor, Eli Muchtar, Taxiarchis V Kourelis, Rahma Warsame, Nelson Leung, Steven R Zeldenrust, John A Lust, S Vincent Rajkumar, Robert A Kyle, William Hogan, Shaji K Kumar
Collection and storage of peripheral blood stem cells (PBSC) for use in autologous stem cell transplantation (ASCT) upon first disease relapse is an accepted practice for eligible patients with multiple myeloma (MM). However, little is known about the factors and outcomes associated with non-utilization of these collected and stored PBSC by MM patients who intended to have a delayed ASCT. From January 1st 2004 to December 31st 2014, we identified 342 patients who underwent collection and storage of their PBSC in anticipation of a delayed ASCT upon first disease relapse...
April 12, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29656050/an-expanded-treatment-protocol-of-panobinostat-plus-bortezomib-and-dexamethasone-in-patients-with-previously-treated-myeloma
#6
Vincent L Hansen, Morton Coleman, Stephanie Elkins, Jeffrey P Letzer, Moshe Yair Levy, Lasika Seneviratne, Jessica Rine, Marina White, Emil T Kuriakose
BACKGROUND: Panobinostat was recently approved by the US Food and Drug Administration and European Commission in combination with bortezomib and dexamethasone for patients with multiple myeloma who have received ≥ 2 regimens, including bortezomib and an immunomodulatory drug. The PANEX (panobinostat expansion) treatment protocol provided access to panobinostat and gathered additional safety data before commercial availability. PATIENTS AND METHODS: In treatment phase 1, patients received panobinostat 20 mg 3 times per week plus bortezomib 1...
March 14, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29650268/efficacy-and-toxicity-profile-of-carfilzomib-based-regimens-for-treatment-of-multiple-myeloma-a-systematic-review
#7
REVIEW
Adeela Mushtaq, Vikas Kapoor, Azka Latif, Ahmad Iftikhar, Umar Zahid, Ali McBride, Ivo Abraham, Irbaz Bin Riaz, Faiz Anwer
Standard induction therapy for multiple myeloma is three-drug combination based on following classes of drugs: proteasome inhibitors, immunomodulators and steroids. Despite its notable efficacy, bortezomib has side effects like peripheral neuropathy (PNP) with reported incidence of grade ≥3 PNP between 2%-23% Schlafer et al., 2017. Carfilzomib (CFZ) has high selectivity and minimal off-target adverse effects including lower rates of PNP. CFZ is already approved for treatment of relapsed and refractory multiple myeloma (RRMM) as single agent as well as in combination with lenalidomide and/or dexamethasone...
May 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29644723/a-french-observational-study-describing-the-use-of-human-polyvalent-immunoglobulins-in-hematological-malignancy-associated-secondary-immunodeficiency
#8
Omar Benbrahim, Jean-François Viallard, Sylvain Choquet, Bruno Royer, Frédéric Bauduer, Olivier Decaux, Jean-Charles Crave, Yann Fardini, Pierre Clerson, Vincent Levy
OBJECTIVE: To describe the characteristics of patients suffering from secondary immunodeficiencies (SID) associated with hematological malignancies (HM), who started immunoglobulins replacement therapy (IgRT), physicians' expectations regarding IgRT and IgRT modalities. METHODS: Non-interventional, prospective French cross-sectional study. RESULTS: The analysis included 231 patients (66±12 years old) suffering from multiple myeloma (MM) (N=64), chronic lymphoid leukemia (CLL) (N=84), aggressive non-Hodgkin B-cell lymphoma (aNHL) (N=32), indolent NHL (N=39), acute leukemia (N=6), Hodgkin disease (N=6)...
April 12, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29628465/-pharmacological-characteristics-and-clinical-study-results-of-the-oral-proteasome-inhibitor-ixazomib-ninlaro-%C3%A2-capsules-2-3-mg-3-mg-and-4-mg
#9
Michiko Machida, Shinichi Fukunaga, Takahito Hara
Ixazomib (Ninlaro® capsule) is an oral small molecule 20S proteasome inhibitor created by Millennium Pharmaceuticals, Inc (Takeda Oncology Company). Ubiquitin proteasome system is a major regulatory system for maintaining protein homeostasis, and an important mechanism for degrading proteins, such as those involved in proliferation regulation, cell cycle regulation and apoptosis, in cells. Ixazomib selectively and reversibly binds to the β5 subunit of the 20S proteasome, inhibits its chymotrypsin-like activity, and thereby accumulates ubiquitinated proteins...
2018: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
https://www.readbyqxmd.com/read/29616871/dcep-as-a-bridge-to-ongoing-therapies-for-advanced-relapsed-and-or-refractory-multiple-myeloma
#10
Hiu Lam Agnes Yuen, Michael Sze Yuan Low, Pasquale Fedele, Anna Kalff, Patricia Walker, Krystal Bergin, John Coutsouvelis, George Grigoriadis, Andrew Spencer
There is limited data describing dexamethasone, cyclophosphamide, etoposide, and cisplatin (DCEP) in relapsed refractory multiple myeloma (RRMM). We reviewed 65 patients with RRMM receiving DCEP between 2005 and 2017 in two Melbourne Hospitals. Patients had received a mean of three prior treatment lines (range, 1-11). The mean number of cycles of DCEP was two (range, 1-4). Overall response rate (ORR) was 55% whilst 19% achieved MR and SD. Median overall survival (OS) was 9.6 months. Those bridged to autologous stem cell transplant (ASCT) had significantly improved OS compared to those who were not (median 32...
April 4, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29616843/phase-1-trial-of-ibrutinib-and-carfilzomib-combination-therapy-for-relapsed-or-relapsed-and-refractory-multiple-myeloma
#11
Ajai Chari, Sarah Larson, Beata Holkova, Robert F Cornell, Cristina Gasparetto, Chatchada Karanes, Jeffrey V Matous, Ruben Niesvizky, Jason Valent, Matthew Lunning, Saad Z Usmani, Larry D Anderson, Lipo Chang, Yihua Lee, Yvonne Pak, Zeena Salman, Thorsten Graef, Elizabeth Bilotti, Saurabh Chhabra
This phase 1, dose-finding study investigated ibrutinib and carfilzomib ± dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma (≥2 lines of therapy including bortezomib and an immunomodulatory agent). Of 43 patients enrolled, 74% were refractory to bortezomib and 23% had high-risk cytogenetics. No dose-limiting toxicities were observed. The recommended phase 2 dose was ibrutinib 840 mg and carfilzomib 36 mg/m2 with dexamethasone. The most common ≥ grade 3 (>10%) treatment-emergent adverse events were hypertension, anemia, pneumonia, fatigue, diarrhea, and thrombocytopenia...
April 4, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29615082/response-and-progression-free-survival-according-to-planned-treatment-duration-in-patients-with-relapsed-multiple-myeloma-treated-with-carfilzomib-lenalidomide-and-dexamethasone-krd-versus-lenalidomide-and-dexamethasone-rd-in-the-phase-iii-aspire-study
#12
Meletios Dimopoulos, Michael Wang, Vladimir Maisnar, Jiri Minarik, William Bensinger, Maria-Victoria Mateos, Mihaela Obreja, Julie Blaedel, Philippe Moreau
BACKGROUND: In ASPIRE, carfilzomib, lenalidomide, and dexamethasone (KRd) significantly improved progression-free survival (PFS) and response rates versus lenalidomide and dexamethasone (Rd) in patients with relapsed multiple myeloma. Per protocol, patients received KRd for a maximum of 18 cycles followed by Rd to progression, so the benefit/risk profile of KRd to progression was not established. METHODS: This post hoc analysis evaluated the efficacy and safety of KRd versus Rd at 18 months from randomization...
April 4, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29610030/clinical-implications-of-targeting-xpo1-mediated-nuclear-export-in-multiple-myeloma
#13
REVIEW
Ujjawal H Gandhi, William Senapedis, Erkan Baloglu, Thaddeus J Unger, Ajai Chari, Dan Vogl, Robert F Cornell
Multiple myeloma (MM) is a malignancy of plasma cells that is typically chronic, and relapse is common. Current therapeutic strategies include combination and sequential treatments with corticosteroids, alkylating agents, proteasomal inhibitors, immunomodulators, and monoclonal antibodies. These drugs prolong survival but ultimately become ineffective. Exportin 1 (XPO1), a nuclear export protein, is overexpressed in MM cells, and knockdown studies have suggested that XPO1 is essential for MM cell survival. Selective inhibitor of nuclear export (SINE) compounds are novel, orally bioavailable class of agents that specifically inhibit XPO1...
March 14, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29606981/pleural-effusion-in-11-14-translocation-q1-multiple-myeloma-in-the-setting-of-proteasome-inhibitor-presents-therapeutic-complexity
#14
Malik Ghannam, Maria Bryan, Erik Kuross, Brent Berry
Background: Primary malignant pleural effusion has been reported in about 134 cases of multiple myeloma (MM). Associated pleural effusions in cases of MM portend a poor prognosis and identifying them is highly relevant. Reported is the case of a man diagnosed with MM who developed primary myelomatous pleural effusion in the setting of multiple relapses and subsequent mortality within 2 months of the pleural effusion diagnosis. Presentation: A 61-year-old African American man was diagnosed with MM in 2011...
2018: Memo
https://www.readbyqxmd.com/read/29605509/the-effects-of-lower-cd34-yields-after-lowe-dose-g-csf-induction-on-long-term-autologous-stem-cell-transplantation-outcome-a-single-center-study
#15
Mohammad Vaezi, Mohammad Shakouri, Maryam Souri, Mohammad Amin Setaredan, Seyed Asadollah Mossavi, Saeed Mohammadi, Kamran Alimoghaddam, Ardeshir Ghavamzadeh
Peripheral blood stem cell transplantation (PBSCT) is an effective treatment for hematological malignancies. Mobilization of peripheral blood stem cells performs in different ways among transplantation centers. Since the Effects of lower CD34+ cells dose after low dose G-CSF induction on autologous stem cell transplantation outcomes are not studied much, so this study was performed for this purpose. 735 autologous stem cell transplanted patients with diagnoses of multiple myeloma (n = 330), Hodgkin lymphoma (n = 200), non-Hodgkin lymphoma (n = 129), acute myeloid leukemia (n = 54) and solid tumors (n = 22) were retrospectively evaluated...
March 23, 2018: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/29603798/the-start-of-a-new-wave-developments-in-proteasome-inhibition-in-multiple-myeloma
#16
REVIEW
Kwee Yong, Sebastian Gonzalez-McQuire, Zsolt Szabo, Paul Schoen, Roman Hajek
Multiple myeloma (MM) accounts for 10% of hematological cancers. Stem cell transplantation remains the cornerstone of first-line treatment for eligible patients but, historically, pharmaceutical treatment options for MM have been limited. The proteasome was identified as a target for MM therapy in the early 2000s and, in 2004, the boronic acid proteasome inhibitor bortezomib gained European approval. Bortezomib now plays a major role in MM treatment, but the duration of its use can be limited by toxicities such as peripheral neuropathy, and the development of resistance...
March 30, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29600238/efficacy-and-tolerability-of-bortezomib-and-dexamethasone-in-newly-diagnosed-multiple-myeloma
#17
Mir Sadaqat Hassan Zafar, Afaq Ahmed Khan, Shyam Aggarwal, Manorama Bhargava
Background: Outcome in multiple myeloma (MM) has improved substantially over recent years as a result of the availability of multiple novel agents with acceptable safety profile. Study Design: Prospective observational study at a tertiary care institute. Methods: Twenty-five newly diagnosed patients of MM were treated with bortezomib and dexamethasone induction with monitoring for response and safety, followed by peripheral blood autologous stem cell transplant (PBASCT) in eligible patients or maintenance...
January 2018: South Asian Journal of Cancer
https://www.readbyqxmd.com/read/29593457/platelet-count-before-peripheral-blood-stem-cell-mobilization-is-associated-with-the-need-for-plerixafor-but-not-with-the-collection-result
#18
Marc-Andrea Baertsch, Katharina Kriegsmann, Petra Pavel, Thomas Bruckner, Michael Hundemer, Mark Kriegsmann, Anthony D Ho, Hartmut Goldschmidt, Patrick Wuchter
Background: A low platelet count before mobilization has recurrently been identified as risk factor for poor mobilization. Methods: To determine the relevance of this finding for peripheral blood stem cell (PBSC) mobilization, including pre-emptive or rescue plerixafor in the case of poor mobilization, we retrospectively analyzed all patients undergoing PBSC collection at our institution between January 2014 and December 2015 (n = 380). Results: In total, 99% of the patients (377/380) successfully collected a minimum of 2 × 106 CD34+ cells/kg body weight sufficient for a single transplant...
January 2018: Transfusion Medicine and Hemotherapy
https://www.readbyqxmd.com/read/29582405/ixazomib-for-relapsed-or-refractory-multiple-myeloma-review-from-an-evidence-review-group-on-a-nice-single-technology-appraisal
#19
REVIEW
Xavier Armoiry, Martin Connock, Alexander Tsertsvadze, Ewen Cummins, G J Melendez-Torres, Pam Royle, Aileen Clarke
Ixazomib is an oral proteasome inhibitor used in combination with lenalidomide plus dexamethasone (IXA-LEN-DEX) and licensed for relapsed or refractory multiple myeloma. As part of a single technology appraisal (ID807) undertaken by the National Institute of Health and Care Excellence, the Evidence Review Group, Warwick Evidence was invited to independently review the evidence submitted by the manufacturer of ixazomib, Takeda UK Ltd. The main source of clinical effectiveness data about IXA-LEN-DEX came from the Tourmaline-MM1 randomized controlled trial in which 771 patients with relapsed or refractory multiple myeloma received either IXA-LEN-DEX or placebo-LEN-DEX as their second-, third-, or fourth-line treatment...
March 26, 2018: PharmacoEconomics
https://www.readbyqxmd.com/read/29582365/evaluation-of-cardiovascular-toxicity-associated-with-treatments-containing-proteasome-inhibitors-in-multiple-myeloma-therapy
#20
Andrea Iannaccone, G Bruno, A Ravera, F Gay, M Salvini, S Bringhen, L Sabia, E Avenatti, F Veglio, A Milan
INTRODUCTION: Recently new treatment options have substantially increased survival for patients with relapsed and/or refractory multiple myeloma (RRMM). Among these, proteasome inhibitors (PI), such as bortezomib and carfilzomib, offer high response rate and prolonged survival. These agents are generally well tolerated but demonstrated a significant cardiovascular toxicity, mostly for regimen containing carfilzomib. AIM: To assess the cardiovascular damage in patients treated with PI for RRMM...
March 26, 2018: High Blood Pressure & Cardiovascular Prevention: the Official Journal of the Italian Society of Hypertension
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