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https://www.readbyqxmd.com/read/28210004/monoclonal-antibody-therapy-in-multiple-myeloma
#1
REVIEW
Cyrille Touzeau, Philippe Moreau, Charles Dumontet
The therapeutic landscape of multiple myeloma (MM) has evolved spectacularly over the past decade with the discovery and validation of proteasome inhibitors and immunomodulatory agents as highly active agents, both in front-line therapy as well as in the relapse and maintenance settings. While previous attempts to apply available monoclonal antibodies (Mabs) to the treatment of patients with MM has until recently been disappointing, novel targets specifically explored in the context of MM have recently lead to the first approvals of Mabs for the treatment of patients with MM...
February 17, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28208219/impact-of-induction-treatment-before-autologous-stem-cell-transplantation-on-long-term-outcome-in-patients-with-newly-diagnosed-multiple-myeloma
#2
Susanna Gassiot, Cristina Motlló, Inuska Llombart, Mireia Morgades, Yolanda González, Montse Garcia-Caro, Josep-Maria Ribera, Albert Oriol
OBJECTIVE: Clinical trials for multiple myeloma patients using novel agent-based regimens before autologous stem cell transplantation (SCT) have shown improvement in response rates and progression-free survival (PFS), however they have failed to identify a significant overall survival (OS) benefit. The aim of this study was to analyze the potential impact of initial induction on the feasibility and outcome of subsequent treatment lines in a real clinical practice setting. METHODS: Consecutive multiple myeloma patients less than 70 years of age diagnosed between 1999 and 2009 were prospectively registered and classified as having received conventional chemotherapy induction regimens with new agents available at relapse (CC cohort, 89 patients) or as treated with novel agents upfront (NA cohort, 65 patients)...
February 16, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28205024/immunomodulatory-drugs-in-multiple-myeloma-mechanisms-of-action-and-clinical-experience
#3
REVIEW
Sarah A Holstein, Philip L McCarthy
Over the last two decades, the outcomes for patients with multiple myeloma, a plasma cell malignancy, have dramatically improved. The development of the immunomodulatory drugs (IMiDs), which include thalidomide, lenalidomide, and pomalidomide, has contributed significantly to these improved outcomes. While thalidomide is now less commonly prescribed, lenalidomide is widely used in the treatment of newly diagnosed transplant-eligible and transplant-ineligible patients, in the maintenance setting post-transplant and in the relapsed/refractory setting, while pomalidomide is currently utilized in the relapsed/refractory setting...
February 16, 2017: Drugs
https://www.readbyqxmd.com/read/28203343/maintenance-therapy-in-multiple-myeloma
#4
REVIEW
Prerna Mewawalla, Abhishek Chilkulwar
Despite recent advances, multiple myeloma remains an incurable disease. Induction therapy followed by autologous transplantation has become the standard of care. The idea of maintenance therapy in multiple myeloma is not new. Starting with chemotherapy in 1975, to interferon in 1998, to novel agents recently, a multitude of agents have been explored in patients with multiple myeloma. In spite of the novel agents, multiple myeloma continues to be an incurable disease with the progression-free survival after autologous transplant rarely exceeding 3 years...
February 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28203342/optimizing-current-and-emerging-therapies-in-multiple-myeloma-a-guide-for-the-hematologist
#5
REVIEW
Shahzad Raza, Rachael A Safyan, Evan Rosenbaum, Alex S Bowman, Suzanne Lentzsch
Multiple myeloma (MM) is the second most common hematologic malignancy. The diagnosis of MM requires ⩾10% clonal plasma cells in the bone marrow or biopsy-proven plasmacytoma, plus evidence of end-organ damage (hypercalcemia, renal failure, anemia, and lytic bone lesions). The definition of MM has recently been expanded to include a ⩾60% clonal plasma cell burden in the bone marrow, serum involved/uninvolved light chain ratio of ⩾100, or more than one focal lesion on magnetic resonance imaging ⩾5 mm in the absence of end-organ damage...
February 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28201977/targeting-the-immune-niche-within-the-bone-marrow-microenvironment-the-rise-of-immunotherapy-in-multiple-myeloma
#6
Klaus Podar, D Jäger
Multiple Myeloma (MM) cells inhibit the development of an effective anti-MM immune response via defects in T cell function, ineffective antigen presentation; reduced phagocytic capacity; natural killer and dendritic cell dysfunction; decreased responsiveness to IL-2 and defects in B cell immunity; upregulation of inhibitory pathways; and production of excessive pro-inflammatory cytokines. Moreover, immune cells including plasmacytoid dendritic cells and macrophages trigger tumor cell proliferation, survival, and drug resistance...
February 13, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28201976/immunomodulatory-drugs-imids-in-multiple-myeloma
#7
Shahzad Raza, Rachael A Safyan, Lentzsch Suzanne
Multiple myeloma (MM) is a plasma cell neoplasm that is incurable with conventional therapy. However, the treatment of MM has dramatically changed since the emergence of immunomodulatory drugs and proteasome inhibitors. The improvements in survival are linked to a deeper understanding of the molecular mechanisms of the disease. Thalidomide, although highly active in MM, is associated with considerable toxicity, particularly in older patients. Immunomodulatory drugs (IMiDs) are structural and functional analogues of thalidomide that represent a promising new class of immunomodulators for treatment of a variety of inflammatory, autoimmune, and neoplastic diseases...
February 13, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28198173/delphi-based-study-and-analysis-of-key-risk-factors-for-invasive-fungal-infection-in-haematological-patients
#8
L Vázquez, M Salavert, J Gayoso, M Lizasoaín, I Ruiz Camps, N Di Benedetto
OBJECTIVE: Mortality caused by invasive fungal infections due to filamentous fungi (IFI-FF) is high. Predisposing factors to IFI-FF are multiple and should be stratified. The objective of this study was to identify key risk factors for IFI-FF in onco-haematological patients in different clinical settings. METHODS: Prospective national Delphi study. Risk factors for IFI-FF in patients with onco-haematological diseases were identified by a systematic review of the literature...
February 14, 2017: Revista Española de Quimioterapia: Publicación Oficial de la Sociedad Española de Quimioterapia
https://www.readbyqxmd.com/read/28194053/cost-effectiveness-of-autologous-stem-cell-treatment-as-compared-to-conventional-chemotherapy-for-treatment-of-multiple-myeloma-in-india
#9
Shankar Prinja, Gunjeet Kaur, Pankaj Malhotra, Gaurav Jyani, Raja Ramachandran, Pankaj Bahuguna, Subhash Varma
Recent innovations in treatment of multiple myeloma include autologous stem cell transplantation (ASCT) along with high dose chemotherapy (HDC). We undertook this study to estimate incremental cost per quality adjusted life year gained (QALY) with use of ASCT along with HDC as compared to conventional chemotherapy (CC) alone in treatment of multiple myeloma. A combination of decision tree and markov model was used to undertake the analysis. Incremental costs and effects of ASCT were compared against the baseline scenario of CC (based on Melphalan and Prednisolone regimen) in the patients of multiple myeloma...
March 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/28190864/successful-management-of-venous-thromboembolism-with-apixaban-in-a-multiple-myeloma-patient-on-lenalidomide-therapy
#10
Satoko Oka, Suguru Takeuchi, Hiroshi Shiragami, Keigo Hamahata, Masaharu Nohgawa
A 69-year-old man was diagnosed with multiple myeloma (IgG-κ) in January 2012. He received autologous hematopoietic stem cell transplantation in August 2012 and subsequently maintained a stringent complete remission. In March 2016, he relapsed and was treated with lenalidomide and low-dose dexamethasone (Ld). On day22, he developed an asymptomatic venous thromboembolism (VTE) despite receiving prophylactic aspirin treatment. Thus, heparin and warfarin were administered. However, his prothrombin time-international normalized ratio did not remain within the target range of 2-3...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28182150/evaluation-of-a-biosimilar-granulocyte-colony-stimulating-factor-filgrastim-xm02-for-peripheral-blood-stem-cell-mobilization-and-transplantation-a-single-center-experience-in-japan
#11
Hideaki Yoshimura, Masaaki Hotta, Takahisa Nakanishi, Shinya Fujita, Aya Nakaya, Atsushi Satake, Tomoki Ito, Kazuyoshi Ishii, Shosaku Nomura
BACKGROUND: Biosimilar granulocyte colony-stimulating factor (G-CSF) has recently been introduced into clinical practice. G-CSFs are used to mobilize CD34(+) cells and accelerate engraftment after transplantation. However, in Asia, particularly in Japan, data for peripheral blood stem cell (PBSC) mobilization by this biosimilar G-CSF are currently lacking. Therefore, the clinical efficacy and safety of biosimilar G-CSF for hematopoietic stem cell transplantation needs to be evaluated in a Japanese context...
2017: Journal of Blood Medicine
https://www.readbyqxmd.com/read/28178364/association-between-response-rates-and-survival-outcomes-in-patients-with-newly-diagnosed-multiple-myeloma-a-systematic-review-and-meta-regression-analysis
#12
Maria Mainou, Anastasia-Vasiliki Madenidou, Aris Liakos, Paschalis Paschos, Thomas Karagiannis, Eleni Bekiari, Efthymia Vlachaki, Zhen Wang, Mohammad Hassan Murad, Shaji Kumar, Apostolos Tsapas
OBJECTIVES: We performed a systematic review and meta-regression analysis of randomized control trials to investigate the association between response to initial treatment and survival outcomes in patients with newly diagnosed multiple myeloma (MM). METHODS: Response outcomes included complete response (CR) and the combined outcome of CR or Very Good Partial Response (VGPR), while survival outcomes were overall survival (OS) and progression free survival (PFS). We used random effects meta-regression models and conducted sensitivity analyses based on definition of CR and study quality...
February 8, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28160288/associations-of-high-dose-melphalan-pharmacokinetics-and-outcomes-in-the-setting-of-a-randomized-cryotherapy-trial
#13
Yu Kyoung Cho, Douglas W Sborov, Misty Lamprecht, Junan Li, Jiang Wang, Erinn M Hade, Yue Gao, Karen Tackett, Nita Williams, Don M Benson, Yvonne A Efebera, Ashley E Rosko, Steven M Devine, Ming Poi, Craig C Hofmeister, Mitch A Phelps
High dose melphalan followed by autologous stem cell transplantation remains standard of care for eligible patients with multiple myeloma, but disease response and toxicity, including severe mucositis, varies among patients. Our randomized trial investigated duration of cryotherapy (2 and 6 hours) for reduction of mucositis prevalence and severity and explored factors associated with variability in pharmacokinetics and outcomes from melphalan therapy. The results demonstrate 2-hour is at least as effective as 6-hour cryotherapy in decreasing severe mucositis...
February 4, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28159578/autologous-hematopoietic-cell-transplantation-in-patients-with-multiple-myeloma-effect-of-age
#14
Binod Dhakal, Ariel Nelson, Guru Subramanian Guru Murthy, Raphael Fraser, Daniel Eastwood, Mehdi Hamadani, Marcello Pasquini, Anita D'Souza, Parameswaran Hari
BACKGROUND: In the novel and pre-novel agent era, high-dose therapy, followed by autologous hematopoietic cell transplantation (AHCT), has been shown to prolong survival in patients with multiple myeloma (MM) in randomized trials. However, these trials only included patients aged ≤ 65 years. Given that the median age at diagnosis is 66 years, it is important to know the outcomes of AHCT in older patients. Similarly, definite outcomes of AHCT in very young patients (aged < 50 years) are also lacking because they represent a very small proportion of patients in clinical trials...
November 25, 2016: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28154088/a-concise-revised-myeloma-comorbidity-index-as-a-valid-prognostic-instrument-in-a-large-cohort-of-801-multiple-myeloma-patients
#15
Monika Engelhardt, Anne-Saskia Domm, Sandra Maria Dold, Gabriele Ihorst, Heike Reinhardt, Alexander Zober, Stefanie Hieke, Corine Baayen, Stefan Jürgen Müller, Hermann Einsele, Pieter Sonneveld, Ola Landgren, Martin Schumacher, Ralph Wäsch
With growing numbers of elderly multiple myeloma patients, reliable tools to assess their vulnerability are required. The objective of this analysis was to develop and validate an easy to use myeloma-risk-score (revised Myeloma Comorbidity Index) that allows risk prediction of OS and PFS differences in a large patient cohort. We conducted a geriatric assessment in 801 consecutive myeloma patients, including comorbidity risks obtained at diagnosis. The cohort was examined within a training and validation set...
February 2, 2017: Haematologica
https://www.readbyqxmd.com/read/28152799/disparity-in-early-mortality-among-racial-groups-with-multiple-myeloma-in-the-united-states-a-national-cancer-data-base-study-of-108-352-patients
#16
Adam C Bartley, Ronald S Go
: 311 Background: Previous population-based studies have shown variations in disease incidence and overall survival (OS) among multiple myeloma (MM) patients (pts) from different ethnic and racial backgrounds. However, the impact of race and ethnicity on early mortality (EM) or death in the first year after the diagnosis of MM is less well known. METHODS: Pts with MM diagnosed from 2000-2011 were identified in the NCDB. We obtained data associated with socio-demographics, type and location of care facility, as well as the use of autologous stem cell transplant (ASCT) as an initial treatment option...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28152765/evaluation-of-relative-thrombocytopenia-identification-of-neuropathy-and-bleeding-risk-secondary-to-utilization-of-neuromodulating-agents-in-multiple-myeloma-patients-receiving-autologous-stem-cell-transplant-treated-with-melphalan-bortezomib-and-lenalidomide
#17
Joel Marcus, Robyn Jackson, Marco A Ruiz, Ryan Patrick Griffin, Rubina Hafeez Khan
: 212 Background: Chemotherapy-induced polyneuropathy (CIPN) is a crippling manifestation in multiple myeloma (MM) patients that requires attentiveness to safety and quality of life.(2) Bortezomib, lenalidomide, and melphalan are commonly utilized chemotherapy agents that can cause both CIPN(3,4) and significant myelosuppression. Within this subset of patients we wish to insure efficacy and minimization of neuropathic pain while being mindful of bleeding risks. METHODS: IRB approval was obtained for a retrospective study of patients with MM who received a bone marrow transplant (BMT)...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28151709/progress-and-paradigms-in-multiple-myeloma
#18
EDITORIAL
Kenneth C Anderson
Remarkable progress has been achieved in multiple myeloma, and patient median survival has been extended 3- to 4-fold. Specifically, there have been 18 newly approved treatments for multiple myeloma in the past 12 years, including seven in 2015, and the treatment paradigm and patient outcome have been transformed. The definition of patients benefitting from these therapies has been broadened. Response criteria now include minimal residual disease (MRD), assessed in bone marrow by multicolor flow cytometry or sequencing, and by imaging for extramedullary disease...
November 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28150872/polymorphism-in-anril-is-associated-with-relapse-in-patients-with-multiple-myeloma-after-autologous-stem-cell-transplant
#19
Ming J Poi, Junan Li, Douglas W Sborov, Zachary VanGundy, Yu Kyoung Cho, Misty Lamprecht, Flavia Pichiorri, Mitch A Phelps, Craig C Hofmeister
Multiple myeloma (MM) is a hematologic malignancy characterized by clonal proliferation of plasma cells and overproduction of monoclonal immunoglobins. Treatment with melphalan is currently standard of care for younger and fit patients when followed by hematopoietic stem cell transplantation (HSCT), and in transplant ineligible patients when used in combination regimens. It has been previously shown that changes in the p53 pathway are associated with melphalan efficacy, but the regulatory role of the p14ARF-MDM2-p53 axis has yet to be fully explored...
February 2, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28147366/what-should-be-done-in-inflammatory-bowel-disease-patients-with-prior-malignancy
#20
REVIEW
Jacques Cosnes
BACKGROUND: Treatment of inflammatory bowel disease (IBD) in patients with prior malignancy is challenging because therapeutic immunosuppression required for controlling IBD activity may increase the risk of cancer recurrence. Key Messages: Contrary to the observations in the post-transplant population, retrospective observational studies of IBD patients with prior malignancy have not demonstrated that immunosuppressive drugs increased significantly the risk of new or recurrent cancer...
2017: Digestive Diseases
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