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Leukemia, multiple myeloma

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https://www.readbyqxmd.com/read/28792782/emerging-antibody-drug-conjugates-for-treating-lymphoid-malignancies
#1
Anna Wolska-Washer, Pawel Robak, Piotr Smolewski, Tadeusz Robak
Antibody-drug conjugates (ADC) are monoclonal antibodies (Mabs) attached to biologically active drugs through specialized chemical linkers. They deliver and release cytotoxic agents at the tumor site, reducing the likelihood of systemic exposure and therefore toxicity. These agents should improve the potency of chemotherapy by increasing the accumulation of the cytotoxic drug within or near the neoplastic cells with reduced systemic effects. Areas covered and methods: A literature review was conducted using the MEDLINE database, PubMed, for articles in English examining Mabs, B-cell receptor pathway inhibitors and immunomodulating drugs...
August 9, 2017: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/28779993/the-class-i-pi3k-inhibitor-s14161-induces-autophagy-in-malignant-blood-cells-by-modulating-the-beclin-1-vps34-complex
#2
Siyu Wang, Jie Li, Yanyun Du, Yujia Xu, Yali Wang, Zubin Zhang, Zhuan Xu, Yuanying Zeng, Xinliang Mao, Biyin Cao
S14161 is a pan-Class I PI3K inhibitor that induces blood cancer cell death, but its mechanism is largely unknown. In the present study, we evaluated the role of S14161 in autophagy, an emerging event in cell destination. Multiple myeloma cell lines RPMI-8226, OPM2, KMS11 and leukemia cell line K562 were treated with S14161. The results showed that S14161 induced autophagy as demonstrated by increased LC3-II and decreased p62, which were prevented by autophagy inhibitors including 3-methyladenine and bafilomycin A1...
July 19, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28761118/bortezomib-before-and-after-high-dose-therapy-in-myeloma-long-term-results-from-the-phase-iii-hovon-65-gmmg-hd4-trial
#3
H Goldschmidt, H M Lokhorst, E K Mai, B van der Holt, I W Blau, S Zweegman, K C Weisel, E Vellenga, M Pfreundschuh, M J Kersten, C Scheid, S Croockewit, R Raymakers, D Hose, A Potamianou, A Jauch, J Hillengass, M Stevens-Kroef, M S Raab, A Broijl, H W Lindemann, G M J Bos, P Brossart, M van Marwijk Kooy, P Ypma, U Duehrsen, R M Schaafsma, U Bertsch, T Hielscher, Le Jarari, H J Salwender, P Sonneveld
The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German-speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial compared bortezomib (BTZ) before and after high-dose melphalan and autologous stem cell transplantation (HDM, PAD arm) compared with classical cytotoxic agents prior and thalidomide after HDM (VAD arm) in multiple myeloma (MM) patients aged 18-65 years. Here, the long-term follow-up and data on second primary malignancies (SPM) are presented. After a median follow-up of 96 months, progression-free survival (censored at allogeneic transplantation, PFS) remained significantly prolonged in the PAD versus VAD arm (hazard ratio (HR)=0...
July 4, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28760306/high-risk-multiple-myeloma-definition-and-management
#4
REVIEW
Nisha S Joseph, Silvia Gentili, Jonathan L Kaufman, Sagar Lonial, Ajay K Nooka
The prognosis of patients with multiple myeloma has significantly improved after the introduction of novel concepts of immunomodulation and proteasome inhibition in myeloma therapies. In conjunction with the use of high-dose therapy and autologous stem cell transplantation, these newer antimyeloma agents facilitated the augmentation of deeper responses and as a result, enhanced survival outcomes. Despite mounting clinical evidence that novel therapies may mitigate the poor prognostic impact of some predictors historically considered "harbingers of doom" in myeloma such as t(4;14), the benefit of these advances is less evident in patients who present with genetically defined high-risk features such as presence of chromosomal abnormalities del17p, t(14;16), or t(14;20), or among patients presenting with plasma cell leukemia...
July 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28758008/bilateral-extramedullary-adrenal-plasmacytoma-case-report-and-review-of-the-literature
#5
REVIEW
Philip J Townend, Gabriel Kraus, Luke Coyle, David Nevell, Anton Engelsman, Stan B Sidhu
Extramedullary plasmacytoma (EMP) accounts for only 3% of plasma cell malignancies; others include multiple myeloma, plasma cell leukemia and solitary plasmacytoma of bone. The majority of EMPs are found in the upper respiratory tract. Other sites include the GI tract, bladder, CNS, thyroid, breast, testes, parotid gland, lymph nodes and skin. There are eight cases in the literature of adrenal plasmacytoma, however, only two were bilateral. We describe our recent experience of bilateral adrenal plasmacytoma and review of the literature...
May 2017: International Journal of Endocrine Oncology
https://www.readbyqxmd.com/read/28754150/characterizing-expanded-access-and-compassionate-use-programs-for-experimental-drugs
#6
Jennifer E Miller, Joseph S Ross, Kenneth I Moch, Arthur L Caplan
OBJECTIVE: We sought to determine the characteristics of "expanded access" and "compassionate use" programs registered in ClinicalTrials.gov and to determine the percentage of drugs provided through these programs that ultimately received FDA marketing approval. RESULTS: We identified 398 expanded access and compassionate use programs (hereafter referred to as expanded access programs) registered on ClinicalTrials.gov. Industry funded 61% (n = 241) of programs individually or collaboratively, while NIH and the US Federal Government rarely funded programs (3% [n = 11] and 2% [n = 6], respectively)...
July 28, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28751289/a-new-case-of-ige-multiple-myeloma-with-review-of-literature
#7
Guillaume Vignon, Anne Sophie Cognée, François Carrere, Isabelle Masson, Florence Borde, Pierre Frédéric Augereau, Philippe Aucher, Franck Lellouche
IgE myeloma is an extremely rare disease characterized by frequent plasma cell leukemia, little monoclonal-spike on electrophoresis, an high incidence of t(11;14) translocation and a worse survival than those with common myelomas. We report here a new case of IgE myeloma and discuss clinical presentation, biological features and therapeutic option.
August 1, 2017: Annales de Biologie Clinique
https://www.readbyqxmd.com/read/28742454/lenalidomide-maintenance-after-autologous-stem-cell-transplantation-in-newly-diagnosed-multiple-myeloma-a-meta-analysis
#8
Philip L McCarthy, Sarah A Holstein, Maria Teresa Petrucci, Paul G Richardson, Cyrille Hulin, Patrizia Tosi, Sara Bringhen, Pellegrino Musto, Kenneth C Anderson, Denis Caillot, Francesca Gay, Philippe Moreau, Gerald Marit, Sin-Ho Jung, Zhinuan Yu, Benjamin Winograd, Robert D Knight, Antonio Palumbo, Michel Attal
Purpose Lenalidomide maintenance therapy after autologous stem-cell transplantation (ASCT) demonstrated prolonged progression-free survival (PFS) versus placebo or observation in several randomized controlled trials (RCTs) of patients with newly diagnosed multiple myeloma (NDMM). All studies had PFS as the primary end point, and none were powered for overall survival (OS) as a primary end point. Thus, a meta-analysis was conducted to better understand the impact of lenalidomide maintenance in this setting. Patients and Methods The meta-analysis was conducted using primary-source patient-level data and documentation from three RCTs (Cancer and Leukemia Group B 100104, Gruppo Italiano Malattie Ematologiche dell'Adulto RV-MM-PI-209, and Intergroupe Francophone du Myélome 2005-02) that met the following prespecified inclusion criteria: an RCT in patients with NDMM receiving ASCT followed by lenalidomide maintenance versus placebo or observation with patient-level data available and achieved database lock for primary efficacy analysis...
July 25, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28741798/novel-orally-bioavailable-ezh1-2-dual-inhibitors-with-greater-antitumor-efficacy-than-an-ezh2-selective-inhibitor
#9
Daisuke Honma, Osamu Kanno, Jun Watanabe, Junzo Kinoshita, Makoto Hirasawa, Emi Nosaka, Machiko Shiroishi, Takeshi Takizawa, Isao Yasumatsu, Takao Horiuchi, Akira Nakao, Keisuke Suzuki, Tomonori Yamasaki, Katsuyoshi Nakajima, Miho Hayakawa, Takanori Yamazaki, Ajay Singh Yadav, Nobuaki Adachi
Polycomb repressive complex 2 (PRC2) methylates histone H3 lysine 27 and represses gene expression to regulate cell proliferation and differentiation. Enhancer of zeste homolog 2 (EZH2) or its close homolog EZH1 functions as a catalytic subunit of PRC2, so there are two PRC2 complexes containing either EZH2 or EZH1. Tumorigenic functions of EZH2 and its synthetic lethality with some subunits of SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complexes have been observed. However, little is known about the function of EZH1 in tumorigenesis...
July 25, 2017: Cancer Science
https://www.readbyqxmd.com/read/28732370/silibinin-an-old-drug-for-hematological-disorders
#10
REVIEW
Hai Zou, Xing-Xing Zhu, Guo-Bing Zhang, Yuan Ma, Yi Wu, Dong-Sheng Huang
Silibinin (silybin), a non-toxic natural polyphenolic flavonoid, is the principal and the most biologically active component of silymarin. It is efficient in the treatment of acute and chronic liver disorders caused by toxins, drug, alcohol, hepatitis, and gall bladder disorders. Further, in our previous studies, we explored the anti-cancer efficacy in common cancers, such as lung, prostatic, colon, breast, bladder, as well as, hepatocellular carcinoma. Interestingly, silibinin is still not solely limited to the treatment of these diseases...
July 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28728749/numb-chin-with-mandibular-pain-or-masticatory-weakness-as-indicator-for-systemic-malignancy-a-case-series-study
#11
Shin-Yu Lu, Shu-Hua Huang, Yen-Hao Chen
BACKGROUND/PURPOSE: Numb chin syndrome (NCS) is a critical sign of systemic malignancy; however it remains largely unknown by clinicians and dentists. The aim of this study was to investigate NCS that is more often associated with metastatic cancers than with benign diseases. METHODS: Sixteen patients with NCS were diagnosed and treated. The oral and radiographic manifestations were assessed. RESULTS: Four (25%) of 16 patients with NCS were affected by nonmalignant diseases (19% by medication-related osteonecrosis of the jaw and 6% by osteopetrosis); yet 12 (75%) patient conditions were caused by malignant metastasis, either in the mandible (62%) or intracranial invasion (13%)...
July 17, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28724539/racial-and-ethnic-disparities-in-hematologic-malignancies
#12
Kedar Kirtane, Stephanie J Lee
Racial and ethnic disparities in patients with solid malignancies have been well documented. Less is known about these disparities in patients with hematologic malignancies. With the advent of novel chemotherapeutics and targeted molecular, cellular, and immunologic therapies, it is important to identify differences in care that may lead to disparate outcomes. This review provides a critical appraisal of the empirical research on racial and ethnic disparities in incidence, survival, and outcomes in patients with hematologic malignancies...
July 19, 2017: Blood
https://www.readbyqxmd.com/read/28696193/living-with-hematologic-cancer-recommendations-solutions
#13
REVIEW
Beth Faiman, Matthew Faiman
Patients with hematologic cancers such as leukemia, lymphoma, and multiple myeloma are living longer than ever. The survival rate of patients with most hematologic cancers has doubled since 1974, and these once-terminal diagnoses are now chronic health conditions. This article reviews the care of patients with hematologic cancers, including those previously treated for childhood, adolescent, and young-adult cancers, discusses the role of primary care in a multidisciplinary team approach, and reviews innovative ways to deliver needed care...
July 2017: Cleveland Clinic Journal of Medicine
https://www.readbyqxmd.com/read/28696175/venetoclax-a-novel-b-cell-lymphoma-2-inhibitor-for-chronic-lymphocytic-leukemia-and-other-hematologic-malignancies
#14
Jacqueline L Olin, Carrie L Griffiths, Morgan B Smith
Patients with chronic lymphocytic leukemia with the 17p deletion have a poor prognosis and treatment options are limited. Venetoclax, a novel B-cell lymphoma-2 inhibitor, has been approved for treatment-experienced chronic lymphocytic leukemia patients with the 17p deletion. A phase 1 dose-escalation study to 400 mg daily showed overall response rates across all doses of 79% with a complete response achieved in 20%. A phase 2 multicenter open-label study demonstrated overall response rate of 79.4% of patients (95% confidence interval 70...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28678969/the-need-for-endodontic-treatment-and-systemic-characteristics-of-hematopoietic-stem-cell-transplantation-patients
#15
Julia Mourão Braga-Diniz, Caroline Christine Santa-Rosa, Renata de Castro Martins, Maria Elisa Souza E Silva, Leda Quercia Vieira, Antônio Paulino Ribeiro Sobrinho
The aim of this study is to investigate the relationship between the epidemiological and clinical profiles of patients before and after hematopoietic stem cell transplantation (HSCT) and the need for endodontic treatment. The subjects included 188 individuals enrolled in the dental care program for transplanted patients of the School of Dentistry, Federal University of Minas Gerais (Faculdade de Odontologia da Universidade Federal de Minas Gerais, FO-UFMG) from March 2011 through March 2016. The patients were subjected to an HSCT conditioning dental regimen based on a thorough clinical and radiographic evaluation...
July 3, 2017: Brazilian Oral Research
https://www.readbyqxmd.com/read/28676669/carfilzomib-resistance-due-to-abcb1-mdr1-overexpression-is-overcome-by-nelfinavir-and-lopinavir-in-multiple-myeloma
#16
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/28670929/exploiting-the-pro-apoptotic-function-of-noxa-as-a-therapeutic-modality-in-cancer
#17
REVIEW
Jeroen E Guikema, Martine Amiot, Eric Eldering
Direct targeting of Bcl-2 members for therapeutic purposes in cancer has become a clinical reality with the FDA approval of ABT-199/Venetoclax. Other highly specific BH3-mimetics are in pre-clinical development. Understanding the functional interactions among the Bcl-2 family is of prime importance to fully exploit their potential. NOXA is considered a rather weak BH3-only member but it has unexplored potential in various settings, which are of relevance in cancer. NOXA is best known as a selective inhibitor of MCL1, itself overexpressed in many cancers, and this protein pair forms an important rheostat in many forms of cell stress...
August 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28663581/heavy-light-chain-monitoring-correlates-with-clinical-outcome-in-multiple-myeloma-patients
#18
M Michallet, C Chapuis-Cellier, T Dejoie, C Lombard, H Caillon, M Sobh, P Moreau, M Attal, H Avet-Loiseau
Novel anti-myeloma agents have improved patient response rates, which are historically based on reductions of the M-protein. These methods can be inaccurate for quantifying M-proteins at low concentrations. We compared the consistency and clinical impact of response assignment by electrophoretic and heavy+light chain (HLC) immunoassays post-consolidation in 463 newly diagnosed patients. The two methods gave similar assignments in patients with partial (PR; 79% agreement) or complete response (⩾CR; 92%). However, in patients achieving very good PR (VGPR) there was poor concordance between methods (45%)...
June 30, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28655925/natural-history-of-t-11-14-multiple-myeloma
#19
A Lakshman, M A Moustafa, S V Rajkumar, A Dispenzieri, M A Gertz, F K Buadi, M Q Lacy, D Dingli, A L Fonder, S R Hayman, M A Hobbs, W I Gonsalves, Y L Hwa, P Kapoor, N Leung, R S Go, Y Lin, T V Kourelis, J A Lust, S J Russell, S R Zeldenrust, R A Kyle, S K Kumar
Translocation (11;14) on interphase FISH in plasma cells is regarded as a standard risk prognostic marker in multiple myeloma (MM) based on studies conducted before introduction of current therapies. We identified 365 patients with t(11;14), and 730 matched controls:132 patients with non-(11;14) translocations and 598 with no chromosomal translocation. The median progression-free survival (PFS) for the three groups were 23.0 (95% CI, 20.8-27.6), 19.0 (95% CI, 15.8-22.7) and 28.3 (95% CI, 25.7-30.6) months respectively [P<0...
June 27, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28642620/pomalidomide-bortezomib-and-low-dose-dexamethasone-in-lenalidomide-refractory-and-proteasome-inhibitor-exposed-myeloma
#20
P G Richardson, C C Hofmeister, N S Raje, D S Siegel, S Lonial, J Laubach, Y A Efebera, D H Vesole, A K Nooka, J Rosenblatt, D Doss, M H Zaki, A Bensmaine, J Herring, Y Li, L Watkins, M S Chen, K C Anderson
This phase 1 dose-escalation study evaluated pomalidomide, bortezomib (subcutaneous (SC) or intravenous (IV)) and low-dose dexamethasone (LoDEX) in lenalidomide-refractory and proteasome inhibitor-exposed relapsed or relapsed and refractory multiple myeloma (RRMM). In 21-day cycles, patients received pomalidomide (1-4 mg days 1-14), bortezomib (1-1.3 mg/m(2) days 1, 4, 8 and 11 for cycles 1-8; days 1 and 8 for cycle ⩾9) and LoDEX. Primary endpoint was to determine the maximum tolerated dose (MTD). Thirty-four patients enrolled: 12 during escalation, 10 in the MTD IV bortezomib cohort and 12 in the MTD SC bortezomib cohort...
June 2, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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