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https://www.readbyqxmd.com/read/28431262/immunologic-approaches-for-the-treatment-of-multiple-myeloma
#1
REVIEW
Leo Rasche, Niels Weinhold, Gareth J Morgan, Frits van Rhee, Faith E Davies
The FDA approval of two monoclonal antibodies in 2015has heralded a new era of targeted immunotherapies for multiple myeloma (MM). In this review we discuss the recent approaches using different immunological components to treat MM. In particular, we review current monoclonal antibody based therapies, engineered T- and NK cell products, 'off-target' immunomodulation, and strategies utilizing allogeneic cell transplantation in MM. We discuss how an immunologic approach offers promise for the treatment of this genetically heterogeneous disease, and how patients with acquired drug resistance may particularly benefit from these therapies...
April 6, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28430745/bortezomib-pharmacokinetics-in-tumor-response-and-peripheral-neuropathy-in-multiple-myeloma-patients-receiving-bortezomib-containing-therapy
#2
Sung-Eun Lee, Kyungmee Choi, Seunghoon Han, Jongtae Lee, Taegon Hong, Gab-Jin Park, Dong-Seok Yim, Chang-Ki Min
The usefulness of pharmacokinetics of bortezomib for multiple myeloma (MM) with respect to the maximum response to bortezomib and bortezomib-induced peripheral neuropathy (BIPN) development was studied. Maximum response to subcutaneous bortezomib therapy and BIPN occurrence for the first 12 weeks of treatment in 35 MM patients treated by bortezomib-dexamethasone (VD) and bortezomib-melphalan-prednisone (VMP) were evaluated. On day 1 of cycle 1, seven whole-blood samples were collected for 3 h after dosing completion to obtain the maximum plasma concentration and area under the time-concentration curve during 3 h postdose (AUC0-3) in each patient...
April 20, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28430175/carfilzomib-lenalidomide-dexamethasone-vs-lenalidomide-dexamethasone-in-relapsed-multiple-myeloma-by-previous-treatment
#3
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/28429426/age-related-health-care-disparities-in-multiple-myeloma
#4
Mathieu Puyade, Gautier Defossez, François Guilhot, Xavier Leleu, Pierre Ingrand
Age is a well-known factor in solid tumours linked to lower adherence to guidelines. Scarce data exist for haematologic malignancies such as multiple myeloma (MM). The aim of the study was to investigate the relationships among age, adherence to guidelines in MM, and overall survival (OS).The Poitou-Charentes cancer registry has exhaustively registered incident cases of MM from 2008 to 2010. Diagnosis, staging, prognosis, and first-line treatment were compared to the international guidelines. Three hundred and sixty-seven patients aged 36 to 93 years were included...
April 21, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28428898/severe-acute-hepatitis-b-in-hbv-vaccinated-partner-of-a-patient-with-multiple-myeloma-treated-with-cyclophosphamide-bortezomib-and-dexamethasone-and-autologous-stem-cell-transplant
#5
Majed M Almaghrabi, Kyle J Fortinsky, David Wong
Hepatitis B reactivation can occur with various forms of immunosuppression. Cyclophosphamide, Bortezomib, and Dexamethasone (CYBOR-D) chemotherapy is commonly used for the treatment of multiple myeloma and has not been noted in guidelines to be causative in HBV reactivation. Indeed, current guidelines do not recommend providing antiviral prophylaxis to patients with prior HBV infection. We present a case of HBV reactivation as a result of CYBOR-D and autologous stem cell transplant which is complicated by the patient's partner who developed acute hepatitis B...
2017: Case Reports in Hepatology
https://www.readbyqxmd.com/read/28428191/the-role-of-minimal-residual-disease-testing-in-myeloma-treatment-selection-and-drug-development-current-value-and-future-applications
#6
Kenneth C Anderson, Daniel Auclair, Gary J Kelloff, Caroline C Sigman, Herve Avet-Loiseau, Ann T Farrell, Nicole J Gormley, Shaji K Kumar, Ola Landgren, Nikhil C Munshi, Michele Cavo, Faith E Davies, Alessandra Di Bacco, Jennifer S Dickey, Steven I Gutman, Howard R Higley, Mohamad A Hussein, J Milburn Jessup, Ilan R Kirsch, Richard F Little, Robert D Loberg, Jens G Lohr, Lata Mukundan, James L Omel, Trevor J Pugh, Gregory H Reaman, Michael D Robbins, A Kate Sasser, Nancy Valente, Elena Zamagni
Treatment of myeloma has benefited from the introduction of more effective and better tolerated agents, improvements in supportive care, better understanding of disease biology, revision of diagnostic criteria, and new sensitive and specific tools for disease prognostication and management. Assessment of minimal residual disease (MRD) in response to therapy is one of these tools, as longer progression-free survival (PFS) is seen consistently among patients who have achieved MRD negativity. Current therapies lead to unprecedented frequency and depth of response, and next generation flow and sequencing methods to measure MRD in bone marrow are in use and being developed with sensitivities in the range of 10(-5)‒10(-6) cells...
April 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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
#7
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/28427509/efficacy-and-safety-of-bortezomib-thalidomide-and-lenalidomide-in-multiple-myeloma-an-overview-of-systematic-reviews-with-meta-analyses
#8
REVIEW
Patricia Melo Aguiar, Tácio de Mendonça Lima, Gisele Wally Braga Colleoni, Sílvia Storpirtis
This overview summarizes evidence for the efficacy and safety of bortezomib, thalidomide, and lenalidomide in patients with multiple myeloma. We searched the Medline, Scopus, and LILACS databases through August 2016, including systematic reviews with meta-analyses of randomized controlled trials assessing the efficacy and/or safety of bortezomib, thalidomide, or lenalidomide in patients with multiple myeloma. Two authors performed study selection, data extraction, and quality assessment using AMSTAR and GRADE instruments...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28426555/creating-artificial-lymphoid-tissues-to-study-immunity-and-hematological-malignancies
#9
Shivem B Shah, Ankur Singh
PURPOSE OF REVIEW: The specialized microenvironments of lymphoid tissue affect immune cell function and progression of disease. However, current animal models are low throughput and a large number of human diseases are difficult to model in animals. Animal models are less amenable to manipulation of tissue niche components, signalling pathways, epigenetics, and genome editing than ex vivo models. On the other hand, conventional 2D cultures lack the physiological relevance to study precise microenvironmental interactions...
April 19, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28425752/use-of-standard-laboratory-methods-to-obviate-routine-dithiothreitol-treatment-of-blood-samples-with-daratumumab-interference
#10
Nicholas J Lintel, Debra K Brown, Diane T Schafer, Farai M Tsimba-Chitsva, Scott A Koepsell, Sara M Shunkwiler
Daratumumab is an antibody currently used in the treatment of patients with refractory multiple myeloma. Blood samples from patients being treated with daratumumab may show panreactivity during pre-transfusion testing. To facilitate the provision of blood components for such patients, it is recommended that a baseline phenotype or genotype be established prior to starting treatment with daratumumab. If patient red blood cells (RBCs) require phenotyping after the start of daratumumab treatment, dithiothreitol (DTT) treatment of the patient's RBCs should be performed...
January 2017: Immunohematology
https://www.readbyqxmd.com/read/28423980/multiple-myeloma-of-the-spine
#11
Arian Lasocki, Frank Gaillard, Simon J Harrison
Radiology provides a crucial clinical adjunct in patients with plasma cell disorders, in particular multiple myeloma, and its uses are evolving and expanding. This pictorial review illustrates the role of imaging throughout the patient's clinical course, with specific reference to recently updated international diagnostic criteria. At presentation, imaging optimises characterisation and staging of the plasma-cell disorder, while later in the course of the disease, its roles include the monitoring of disease progression, assessment of post-treatment response and the investigation of clinical deterioration...
January 1, 2017: Neuroradiology Journal
https://www.readbyqxmd.com/read/28423741/lenalidomide-and-the-risk-of-serious-infection-in-patients-with-multiple-myeloma-a-systematic-review-and-meta-analysis
#12
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/28420651/anorectal-involvement-in-a-patient-with-multiple-myeloma
#13
Pedro Russo, Ana Luisa Tomé, Tiago Capela, Maria João Bettencourt
Multiple myeloma is a neoplastic proliferation of monoclonal plasma cells. Symptomatic gastrointestinal involvement is uncommon. We report the case of a 45-year-old patient admitted with an anorectal polypoid lesion, which progressed to colonic obstruction. Investigation revealed a secondary plasmacytoma associated with multiple myeloma. We discuss the characteristics of this rare entity with poor prognosis, its clinical implications and treatment options.
April 18, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28419431/moving-beyond-maximum-tolerated-dose-for-targeted-oncology-drugs-use-of-clinical-utility-index-to-optimize-venetoclax-dosage-in-multiple-myeloma-patients
#14
Kevin J Freise, Aksana K Jones, Maria E Verdugo, Rajeev M Menon, Paulo C Maciag, Ahmed Hamed Salem
Exposure-response analyses of venetoclax in combination with bortezomib and dexamethasone in previously treated patients with multiple myeloma (MM) were performed on a Phase 1b venetoclax dose-ranging study. Logistic regression models were utilized to determine relationships, identify sub-populations with different responses and optimize the venetoclax dosage that balanced both efficacy and safety. Bortezomib refractory status and number of prior treatments were identified to impact the efficacy response to venetoclax treatment...
April 17, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28418282/immunohistochemical-detection-of-hairy-cell-leukemia-in-paraffin-sections-the-role-of-pax5-and-cd103-double-staining-to-improve-specificity-and-sensitivity
#15
Igor B Rozenvald, Maurice D Richardson, Lenessa Brock, Russell L Maiese
CONTEXT: - In hematopathology practice, abnormal expression of CD103 on B cells is detected by flow cytometry in hairy cell leukemia (HCL) and, in combination with other phenotypic and morphologic findings, provides diagnostic specificity and sensitivity. Immunostaining on paraffin sections makes it possible to perform immunophenotyping in situ. However, normal bone marrow contains CD103-positive cells, which are not B cells, making it difficult to be certain about low-level involvement by HCL...
April 18, 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/28416490/preclinical-characterization-of-bet-family-bromodomain-inhibitor-abbv-075-suggests-combination-therapeutic-strategies
#16
Mai H Bui, Xiaoyu Lin, Daniel H Albert, Leiming Li, Lloyd T Lam, Emily J Faivre, Scott Warder, Xiaoli Huang, Denise Wilcox, Cherrie K Donawho, George S Sheppard, Le Wang, Steve Fidanze, John K Pratt, Dachun Liu, Lisa Hasvold, Tamar Uziel, Xin Lu, Fred Kohlhapp, Guowei Fang, Steven W Elmore, Saul H Rosenberg, Keith F McDaniel, Warren M Kati, Yu Shen
ABBV-075 is a potent and selective BET family bromodomain inhibitor that recently entered Phase I clinical trials. Comprehensive preclinical characterization of ABBV-075 demonstrated broad activity across cell lines and tumor models representing a variety of hematological malignancies and solid tumor indications. In most cancer cell lines derived from solid tumors, ABBV-075 triggers prominent G1 cell cycle arrest without extensive apoptosis. In this study, we show that ABBV-075 efficiently triggers apoptosis in acute myeloid leukemia (AML), non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM) cells...
April 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28415782/glutaminase-inhibitor-cb-839-synergizes-with-carfilzomib-in-resistant-multiple-myeloma-cells
#17
Ravyn M Thompson, Dominik Dytfeld, Leticia Reyes, Reeder M Robinson, Brittany Smith, Yefim Manevich, Andrzej Jakubowiak, Mieczyslaw Komarnicki, Anna Przybylowicz-Chalecka, Tomasz Szczepaniak, Amit K Mitra, Brian G Van Ness, Magdalena Luczak, Nathan G Dolloff
Curative responses in the treatment of multiple myeloma (MM) are limited by the emergence of therapeutic resistance. To address this problem, we set out to identify druggable mechanisms that convey resistance to proteasome inhibitors (PIs; e.g., bortezomib), which are cornerstone agents in the treatment of MM. In isogenic pairs of PI sensitive and resistant cells, we observed stark differences in cellular bioenergetics between the divergent phenotypes. PI resistant cells exhibited increased mitochondrial respiration driven by glutamine as the principle fuel source...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413546/solitary-plasmacytoma-of-temporal-bone-a-rare-case-report
#18
Ritesh Kumar, Narendra Kumar, Sandeep Mohindro, B D Radotra
Solitary plasmacytoma of base of skull is a rare disease. It presents with headache, swelling, and other vague symptoms. Systemic work-up to rule out multiple myeloma is necessary. Radiotherapy is the treatment of choice. We, here, present a case of solitary plasmacytoma of base of skull in right temporal bone in a 50-year-old female treated with surgery and radiotherapy.
January 2017: Asian Journal of Neurosurgery
https://www.readbyqxmd.com/read/28413157/long-term-stabilisation-of-myeloma-with-curcumin
#19
Abbas Zaidi, Maggie Lai, Jamie Cavenagh
Myeloma is a haematological malignancy which typically follows a relapsing-remitting course. While treatment can control the myeloma and improve quality of life for given periods of time, remissions generally become progressively shorter with subsequent relapses, and patients ultimately enter a final refractory phase. To help control symptoms and enhance quality of life, some patients use complementary therapies as an adjunct to their conventional therapy. Here, we describe a myeloma patient who started a daily dietary supplement of curcumin when approaching her third relapse...
April 16, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28412987/back-pain-in-the-emergency-department-pathological-fracture-following-spinal-manipulation
#20
Christopher Skappak, Erik J Saude
Back pain is one of the most common presentations to the emergency department. Though case reports of patients presenting with increased back pain following chiropractic spinal manipulations are rare, we have identified a case rarely reported in the literature where a potential injury from chiropractic manipulation resulted in a diagnosis of multiple myeloma. We have reported a previously healthy 66-year-old male who presented with persistent lower back pain over 4 weeks. An initial evaluation with thoracolumbar radiographs revealed no significant findings...
April 17, 2017: CJEM
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