Uncategorized

Autoimmune Neutropenia of Infancy,Prevalence of Pseudomonas Skin Infections

Autoimmune Neutropenia of Infancy- Unexpected Prevalence of Pseudomonas Skin Infections
http://www.bloodjournal.org/content/132/Suppl_1/4940

Nov 21st, 2018 – Background: Autoimmune neutropenia of infancy (AIN), the most frequent type of severe neutropenia in young children, occurs due to recognition of membrane antigens by anti-neutrophil antibodies, resulting in peripheral neutrophil destruction. Despite the often severe and prolonged neutropenia, serious infectious complications are less frequent in AIN compared with other etiologies of severe neu…

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Allergic Rhinitis Center


Putative Microbial Population Shifts Attributable to Nasal Administration of Streptococ…
Preview
https://www.ncbi.nlm.nih.gov/pubmed/30535674
Probiotics and Antimicrobial Proteins; De Grandi R, Drago L et. al.

Dec 12th, 2018 – Changes in bacterial composition of nasal microbiota may alter the host’s susceptibility to several infectious and allergic diseases such as chronic rhinosinusitis and allergic rhinitis. The aim of this study was to evaluate the effects of 1-week …

Nasal nitric oxide in the inferior turbinate surface decreases with intranasal steroids… Preview
https://www.ncbi.nlm.nih.gov/pubmed/30527902
Auris, Nasus, Larynx; Takahara D, Kono T et. al.

Dec 12th, 2018 – It remains controversial whether nasal nitric oxide (NO) serves as a reliable parameter to evaluate treatment efficacy in patients with allergic rhinitis (AR). The measurement of local nasal NO levels has been shown to be a sensitive marker for th…

Prospective observational study validating the German version of the Control of Allergi… Preview
https://www.ncbi.nlm.nih.gov/pubmed/30514843
NPJ Primary Care Respiratory Medicine; Werner CU, Koch L et. al.

Dec 6th, 2018 – The Control of Allergic Rhinitis and Asthma Test (CARAT10), developed by Portuguese experts, is the only questionnaire assessing asthma control under additional consideration of a frequently concurrent allergic rhinitis (AR), providing sub-scores …

Discriminating severe seasonal allergic rhinitis. Results from a large nation-wide data… Preview
https://www.ncbi.nlm.nih.gov/pubmed/30485327
PloS One; Caimmi D, Baiz N et. al.

Nov 28th, 2018 – Allergic rhinitis (AR) is a chronic disease affecting a large amount of the population. To optimize treatment and disease management, it is crucial to detect patients suffering from severe forms. Several tools have been used to classify patients a…

Der p 1-specific regulatory T cell response during house dust mite allergen immunotherapy. Preview
https://www.ncbi.nlm.nih.gov/pubmed/30485456
Allergy Boonpiyathad T, Sokolowska M et. al.

Nov 28th, 2018 – Allergen-specific immunotherapy (AIT) is the only available treatment for allergic diseases that can induce specific immune tolerance to allergens. The key mechanisms involved in this process include changes in allergen-specific regulatory T (Treg…

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Guidelines 9 results

Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines-2016 revision. Preview
https://www.ncbi.nlm.nih.gov/pubmed/28602936
The Journal of Allergy and Clinical Immunology; Brożek JL, Bousquet J et. al.

Jun 13th, 2017 – Allergic rhinitis (AR) affects 10% to 40% of the population. It reduces quality of life and school and work performance and is a frequent reason for office visits in general practice. Medical costs are large, but avoidable costs associated with lo…

Clinical practice guideline: Allergic rhinitis. Preview
https://www.ncbi.nlm.nih.gov/pubmed/25644617
Otolaryngology–head and Neck Surgery : Official Journal of American Academy of Otolaryngology-Head and Neck Surgery; Seidman MD, Gurgel RK et. al.

Feb 4th, 2015 – Allergic rhinitis (AR) is one of the most common diseases affecting adults. It is the most common chronic disease in children in the United States today and the fifth most common chronic disease in the United States overall. AR is estimated to aff…

Clinical practice guideline: allergic rhinitis executive summary.Preview
https://www.ncbi.nlm.nih.gov/pubmed/25645524
Otolaryngology–head and Neck Surgery : Official Journal of American Academy of Otolaryngology-Head and Neck Surgery; Seidman MD, Gurgel RK et. al.

Feb 4th, 2015 – The American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF) has published a supplement to this issue featuring the new Clinical Practice Guideline: Allergic Rhinitis. To assist in implementing the guideline recommendations, …

Practical guide to skin prick tests in allergy to aeroallergens.Preview
https://www.ncbi.nlm.nih.gov/pubmed/22050279
Allergy Bousquet J, Heinzerling L et. al.

Nov 5th, 2011 – This pocket guide is the result of a consensus reached between members of the Global Allergy and Asthma European Network (GA(2) LEN) and Allergic Rhinitis and its Impact on Asthma (ARIA). The aim of the current pocket guide is to offer a comprehen…

Immunotherapy for allergic rhinitis. Preview
https://www.ncbi.nlm.nih.gov/pubmed/21848757
Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology; Walker SM, Durham SR et. al.

Aug 19th, 2011 – Allergic rhinitis (AR) affects more than 20% of the population in the United Kingdom and western Europe and represents a major cause of morbidity that includes interference with usual daily activities and impairment of sleep quality. This guidance…

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Drugs 1,283 results see all →

Clinicaltrials.gov 1,227 results

Effects of Intranasal Fluticasone Plus Azelastine on Airway Inflammation in Patients With Asthma & Allergic Rhinitis
https://clinicaltrials.gov/ct2/show/NCT02953106

Oct 31st, 2018 – The unified allergic airway describes patients who have both asthma and allergic rhinitis. Both conditions have similar underlying pathophysiology in terms of T-helper 2 (Th2) cell activation. Patients with unified allergic airway disease have a g…

Seinäjoki Adult Asthma Study
https://clinicaltrials.gov/ct2/show/NCT02733016

Oct 26th, 2018 – At baseline visit the diagnostic studies performed were: spirometry, PEF (peak expiratory flow) follow-up, other respiratory physiology measurements, laboratory, skin-prick, AQ20 (Airways questionnaire 20), 15D, background data. At follow-up visit…

Study to Investigate Effects of CAL-101 in Subjects With Allergic Rhinitis Exposed to Allergen in an Environmental Chamber
https://clinicaltrials.gov/ct2/show/NCT00836914

Oct 23rd, 2018 – A Phase I, randomized, double-blind crossover study of CAL-101, an oral inhibitor of phosphatidylinositol 3-kinase (PI3K) delta, in patients with allergic rhinitis.

Study on Association Between Treatment of Allergic Rhinitis and Cognitive Ability in Children
https://clinicaltrials.gov/ct2/show/NCT03714945

Oct 22nd, 2018 – INTRODUCTION Allergic rhinitis is the reportedly second most common reported chronic health condition in Hong Kong children under the age of 14, with the Child Health Survey 2005-2006 indicating a prevalence of 24.5%. Allergic rhinitis is a type I…

Effects of Broccoli Sprout Extract on Allergy Rhinitis
https://clinicaltrials.gov/ct2/show/NCT02885025

Oct 18th, 2018 – Allergic rhinitis is a common illness suffered among US Veterans. Despite the availability of medications, many patients fail to get adequate control of symptoms especially in high pollutant areas. Southern California air pollutants, like diesel e…

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News 567 results

Gestational, umbilical cord vitamin D levels don’t predict atopic disease in offspring
https://www.mdedge.com/obgyn/article/190119/obstetrics/gestational-umbilical-cord-vitamin-d-levels-dont-predict-atopic
Jeff Craven

Dec 3rd, 2018 – Vitamin D levels measured in maternal sera during gestation and in umbilical cord blood were not predictive of the prevalence of eczema, food allergy, asthma and allergic rhinitis in children at ages 2 years and 5 years, according to study results.

Allergy Testing in Dermatology and Beyond
https://www.mdedge.com/cutis/article/189678/practice-management/allergy-testing-dermatology-and-beyond
MDedge Dermatology; Ashley D. Lundgren, MD

Nov 28th, 2018 – Allergy testing typically refers to evaluation of a patient for suspected type I or type IV hypersensitivity. 1,2 The possibility of type I hypersensitivity is raised in patients presenting with food allergies, allergic rhinitis, asthma, and immedi.

New Drug Combinations for Asthma, COPD at CHEST 2018
https://www.medscape.com/viewarticle/902774

Oct 1st, 2018 – SAN ANTONIO — New combinations of known and experimental drugs will be explored at the American College of Chest Physicians Annual Meeting as the pharmaceutical search for better control of asthma and chronic obstructive pulmonary disease (COPD) c…

Fast Five Quiz: Test Your Knowledge About Fall Allergies
https://www.medscape.com/viewarticle/884925

Sep 21st, 2018 – Although many people associate allergies with the growth and development of plants in spring and summer, allergic symptoms are very common in the fall as well. Ragweed is the biggest allergy trigger during the fall season, but mold, dust mites, an…

Advise parents on validity of AD-associated conditions
https://www.mdedge.com/familypracticenews/article/172058/atopic-dermatitis/advise-parents-validity-ad-associated-conditions
Heidi Splete, Family Practice News

Aug 7th, 2018 – Atopic dermatitis is becoming more prevalent in the industrialized world, along with other atopic disorders, including allergic rhinitis and asthma, according to Douglas W. Kress, MD, of the department of dermatology at the University of Pittsburg.

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Uncategorized

Leukemia Lymphoma Myelodysplastic Syndromes (MDS) Myeloma Myeloproliferative Neoplasms (MPNs)

A Phase 2 Study of Actinium-225 (225Ac)-Lintuzumab in Older Patients with Untreated Acute Myeloid Leukemia (AML) – Interim Analysis of 1.5 µci/Kg/Dose
http://www.bloodjournal.org/content/132/Suppl_1/1457

Nov 21st, 2018 – Background: Older patients (pts) with AML unfit for intense induction chemotherapy have a poor prognosis with a 5 year survival of <10%. 225Ac-lintuzumab is composed of 225Ac linked to a humanized anti-CD33 monoclonal antibody. Data were previously presented on the initial 13 pts who received 2.0 µCi/kg/dose on Days 1 and 8 (ASH, 2017, Abstract 616). Although that dose resulted in a high respon…

64cu-DOTA-Anti-CD33 PET-CT Imaging for Acute Myeloid Leukemia and Image-Guided Treatment
http://www.bloodjournal.org/content/132/Suppl_1/2747

Nov 21st, 2018 – Introduction: Acute myeloid leukemia (AML) is a highly aggressive form of leukemia that results a poor survival outcome. Currently, diagnosis and prognosis are based on invasive single-point bone marrow biopsies (iliac crest). Although non-invasive positron emission tomography (PET) imaging has been developed for almost all solid tumors and some hematological malignancies, there is currently no…

Cell Type-Specific Deregulation of Polypyrimidine Tract- Binding Proteins (PTBPs) Drive Aberrant Splicing in Multiple Myeloma (MM) and Acute Myeloid Leukemia (AML)
http://www.bloodjournal.org/content/132/Suppl_1/3895

Nov 21st, 2018 – Genome-wide transcriptome profiling detected an increased splicing alterations in MM and AML. While these malignancies are derived from different cell linages, their tumor cells acquire similar aberrant splicing (AbSp), mostly intron retentions. To delineate AbSp mechanism in MM/AML, we focused on PTBPs (1/2/3) that play a critical role in intron excision. We have previously reported deregulate…

Clinical Characteristics and Outcome of Patients with Wild-Type Transthyretin and AL Cardiac Amyloidosis Confirmed By Mass Spectrometry
http://www.bloodjournal.org/content/132/Suppl_1/3126

Nov 21st, 2018 – INTRODUCTION: Cardiac involvement is common in both wild-type transthyretin (wATTR) and AL amyloidosis and these entities can have overlapping clinical features (Banypersad et al, JAHA 2012). Accurate diagnosis is vital given differences in spectrum of disease, management, and prognosis. We examined the presenting clinical features and survival outcome of patients diagnosed with cardiac wATTR a…

Single Doses of Antibody Drug Conjugates (ADCs) Targeted to CD117 or CD45 Have Potent In Vivo Anti-Leukemia Activity and Survival Benefit in Patient Derived AML Models
http://www.bloodjournal.org/content/132/Suppl_1/3316

Nov 21st, 2018 – Background. Allogeneic bone marrow transplant (BMT) is a potentially curative approach in patients with refractory or high risk hematologic malignancies, such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Prior to transplant, patients are prepared with non-specific, high dose chemotherapy alone or in combination with total body irradiation, which are associated with early…

Extracellular Vesicles (EVs) Shape the Leukemic Microenvironment
http://www.bloodjournal.org/content/132/Suppl_1/5428

Nov 21st, 2018 – Background Extracellular Vesicles (EVs) compose a naturally occurring, heterogeneous group of membrane-bound, nano-sized particles shed by all cells. Depending on cellular type, physiological state, and mode of secretion some harbor potent regenerative properties while others have the propensity to induce disease. Human bone marrow mesenchymal stem cell (MSC)-derived EVs harbor regenerative pot…

Systematic Review of Non-Conventional Dosing of Oral Anticancer Therapies in Malignant Haematology
http://www.bloodjournal.org/content/132/Suppl_1/5915

Nov 21st, 2018 – Introduction Survival outcomes for patients with lymphoid, myeloid and plasma cell malignancies, have improved with the use of oral small molecule inhibitory agents. Oral anti-cancer therapies are often administered continuously and can have significant side-effects, which can adversely impact adherence, quality of life (QoL) and survival outcomes. In order to improve tolerability, non-standard…

The Impact of a Physical Activity Intervention Can be Accurately Assessed By Smart Watches in Patients Completing Autologous Stem Cell Transplantation for Lymphoma or Multiple Myeloma: Results of a…
http://www.bloodjournal.org/content/132/Suppl_1/5911

Nov 21st, 2018 – Background: Based on cohort studies and a limited number of prospective studies, physical activity (PA) can improve quality of life (QoL) in non-Hodgkin lymphoma (NHL), multiple myeloma (MM), and patients (pts) undergoing autologous stem cell transplant (ASCT). There are also data to suggest that survival (Pophali et al, ASH 2017) is improved with increased PA in NHL pts. After ASCT, it is know…

Pegfilgrastim Versus Filgrastim in the Management of Therapy-Related Neutropenia in Relapsed and Refractory Multiple Myeloma in Treatment with Pomalidomide-Dexamethasone
http://www.bloodjournal.org/content/132/Suppl_1/5905

Nov 21st, 2018 – Aims: The objective of this study was to compare the efficacy and safety of pegfilgrastim in patients affected by heavily pretreated MM, treated with pomalidomide-dexamethasone, in order to determine whether a single subcutaneous injection of pegfilgrastim is as effective as daily injections of standard filgrastim, in terms of haematological toxicity, febrile neutropenic episodes, antibiotic us…

Monitoring Minimal Residual Disease in Acute Myeloid Leukemia Using Genomic or cfDNA with MyMRD®, a Targeted NGS Panel
http://www.bloodjournal.org/content/132/Suppl_1/5268

Nov 21st, 2018 – Acute myeloid leukemia (AML) is a genetically and phenotypically heterogeneous disorder. Precision therapies for AML have been developed that target specific driver mutations. The efficacies of these therapies are variable, making it critical to determine successful therapies prior to patient relapse. For patients achieving a first complete remission, minimum residual disease (MRD) is an import…

An Exploratory Study of Cytokine Markers of Cancer-Related Cognitive Impairment in Hematological Malignancy
http://www.bloodjournal.org/content/132/Suppl_1/5914

Nov 21st, 2018 – Introduction. Cancer-related cognitive impairment is a distressing symptom that affects numerous patients after cancer therapy, including those treated for hematological malignancy. The lack of effective interventions has driven interest in determining underlying mechanisms. Accumulating evidence in the context of solid tumours suggests inflammatory processes are involved in the development of …

A Twenty Years Epidemiology Study of 2nd Hematological Malignancies Post to the Initial Tumor Treatment: Report from Southern China Single Cancer Group
http://www.bloodjournal.org/content/132/Suppl_1/5903

Nov 21st, 2018 – Objective: To investigate the clinical features of 2nd hematological malignancies post to the initial cancer treatment. METHODS: A retrospective study was performed to analyze the available clinical data of 116 patients diagnosed with 2nd hematologic malignancies after treatment of various malignant tumors from June 1998 to June 2018 at Sun Yat-sen University cancer center. RESULTS: The charact…

Identification and Characterization of Potential Candidates for Treatment Targeting Apoptosis Pathways in Patients with Hematological Neoplasms
http://www.bloodjournal.org/content/132/Suppl_1/4098

Nov 21st, 2018 – Background: Resistance to apoptosis is one of the hallmarks in hematological neoplasms, most typically via dysregulation of the intrinsic mitochondrial pathway. The most important antiapoptotic/pro-survival proteins in this pathway are BCL2, BCL2L1 and MCL1. Molecules targeting each of these proteins are in various stages of preclinical and clinical development. The BCL2 inhibitor venetoclax is…

Natural History of Asymptomatic IgM Monoclonal Gammopathies: Impact of the Bone Marrow Aspiration into the Classification and Prognosis
http://www.bloodjournal.org/content/132/Suppl_1/1610

Nov 21st, 2018 – Introduction: As in multiple myeloma, Waldenström macroglobulinemia (WM) is preceded by an asymptomatic phase, mainly as monoclonal gammopathy of undetermined significance (MGUS) or by a smoldering WM (SWM) phase. It has recently been reported that patients with IgM MGUS have a higher risk of progression in comparison to those with other MGUS isotypes. Moreover, it has been described that if th…

Targeting the Glyco-Antigen CD75s with the Tetravalent, Fc-Engineered Antibody ‘Ebu-141 Tetra’ Induces Potent Killing of B Cell Lymphoma and Plasma Cell Tumors
http://www.bloodjournal.org/content/132/Suppl_1/4178

Nov 21st, 2018 – While monoclonal antibodies (MoAb) are already well established for the treatment of B cell-derived malignancies and usually show a good safety profile, not all patients benefit and relapses may be a problem. In order to identify novel surface structures suitable for antibody-based therapies and to improve killing mechanisms, ‘EBU-141 Tetra’ was developed. The parental MoAb EBU-141 is of mouse …

A New Prognostic Index for Waldenström Macroglobulinemia Based on a Multicenter Retrospective Study of the Japanese Society of Myeloma
http://www.bloodjournal.org/content/132/Suppl_1/5320

Nov 21st, 2018 – Background: We recently reported that the International Prognostic Scoring System for Waldenström macroglobulinemia (ISSWM), which is widely used to predict the prognosis of WM patients, might not be applicable to Japanese patients, and evidence of pleural effusion might be a novel adverse prognostic factor for symptomatic WM in the rituximab era. Further studies with a large number of patients…

Evaluation of T Cell and Monocyte Immune Subsets in the Stem Cell Product of Patients Developing Engraftment Syndrome Following Autologous Stem Cell Transplantation for Multiple Myeloma and Lymphoma
http://www.bloodjournal.org/content/132/Suppl_1/4604

Nov 21st, 2018 – BACKGROUND: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is now standard of care for newly diagnosed patients with multiple myeloma (MM) and is used for some forms of non-Hodgkin lymphoma, providing improved outcomes. ASCT has been associated with a high incidence of engraftment syndrome (ES), which clinically presents as skin rashes, diarrhea, non-infectious f…

Efficacy of a New Small-Molecule Inhibitor of Histone Deacetylase 6 (HDAC6) in Preclinical Models of B-Cell Lymphoma and Acute Myeloid Leukemia
http://www.bloodjournal.org/content/132/Suppl_1/5383

Nov 21st, 2018 – Histone deacetylase 6 (HDAC6) is a protein modifier that is an increasingly attractive pharmacological target. Interestingly, the observation that the HDAC6 knock-out mouse is not lethal, in contrast to those undergoing complete loss of class I, II and III HDACs, suggests that specific HDAC6 inhibitors may be better tolerated than pan-HDAC inhibitors or drugs that target the other HDAC classes….

SLAMF7 in Primary Effusion Lymphoma, Target for Individualized Therapy?
http://www.bloodjournal.org/content/132/Suppl_1/5300

Nov 21st, 2018 – Primary effusion lymphoma (PEL) is a rare, aggressive form of B-cell lymphoma. With a median survival time of around six months the prognosis for PEL patients is poor. Therefore, there is a medical need for novel therapeutic strategies. We performed expression array analysis to find potential targets for antibody-based therapy. Unsupervised clustering analysis revealed that PEL cell lines group…

Frequency of Acquired Genetic Mutations and Their Prognostic Impact on Patients with Incidental Finding of Isolated 20q- in Bone Marrow without Morphologic Evidence of a Myeloid Neoplasm
http://www.bloodjournal.org/content/132/Suppl_1/4382

Nov 21st, 2018 – Introduction Myelodysplastic syndromes (MDS) are heterogeneous myeloid disorders characterized by dysplasia in one or more hematopoietic cell lines, peripheral cytopenia(s), and distinct cytogenetic abnormalities. The presence of certain cytogenetic abnormalities [e.g. 7/del(7q), -5/del(5q), 13/del(13q), i(17p)], in the setting of unexplained persistent cytopenia, has been considered presumptiv…

Bion-1301 Blocks APRIL-Induced Anti-Apoptotic Signaling, Immune Suppressive Phenotype, and Chemokine Production Associated with Multiple Myeloma
http://www.bloodjournal.org/content/132/Suppl_1/1908

Nov 21st, 2018 – A proliferation-inducing ligand (APRIL) is produced by multiple accessory and myeloid cells in the bone marrow niche. Through binding to its receptors B-cell maturation antigen (BCMA) and transmembrane activator and CAML interactor (TACI), APRIL plays an important role in the development and maintenance of cells derived from the B cell lineage. Both APRIL and its receptors have been identified …

Solid Tumors in Post-Polycythemia Vera and Post-Essential Thrombocythemia Myelofibrosis: A Study on 2220 Patients
http://www.bloodjournal.org/content/132/Suppl_1/3039

Nov 21st, 2018 – Background: Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms (MPN) that can progress to post-PV (PPV) myelofibrosis (MF) and post-ET (PET) MF, from now on referred to as secondary myelofibrosis (SMF). Recent studies have shown an increased risk of developing solid tumors (ST) in MPN patients in comparison to the general population. Information on develo…

18f-FDG PET/CT and the Revised International Staging System Are More Discriminating of Survival Outcomes in Newly Diagnosed Multiple Myeloma
http://www.bloodjournal.org/content/132/Suppl_1/4483

Nov 21st, 2018 – Purpose : This study evaluated the prognostic role of 18F-FDG PET/CT at baseline in patients with newly diagnosed multiple myeloa (MM) and evaluated the prognostic relevance of 18F-FDG PET/CT for each stage according to the Revised International Staging System (R-ISS). Method: We retrospectively analyzed the records of 167 patients with newly diagnosed MM. 18F-FDG PET/CT was performed prior to …

A Phase 2 Study of Carfilzomib Plus Elotuzumab Plus Dexamethasone for Myeloma Patients Relapsed after 1-3 Prior Treatment Lines
http://www.bloodjournal.org/content/132/Suppl_1/1975

Nov 21st, 2018 – Introduction: The median progression free survival (PFS) and overall survival (OS) of multiple myeloma (MM) patients have been prolonged due to novel agents combined with ASCT but the median OS in MM is still 7-8 years. Thus, the feasibility of new combinations and dosing of available agents must be investigated. The first proteasome inhibitor (PI), bortezomib (B), combined with elotuzumab and …

Carfilzomib Cardiovascular Disease: Use of the Atherosclerotic Cardiovascular Disease Score to Predict Cardiovascular Events in Multiple Myeloma Patients Treated with Carfilzomib
http://www.bloodjournal.org/content/132/Suppl_1/3254

Nov 21st, 2018 – Introduction: In the ASPIRE and ENDEAVOR trials, multiple myeloma (MM) patients treated with carfilzomib (K) had significantly improved progression‐free survival and overall survival compared with standard of care. The incidence of all-grade adverse cardiovascular events (ACVE) was 26.6% and 24.5% in the K treated groups in ASPIRE and ENDEAVOR respectively. The atherosclerotic cardiovascular di…

A Phase II Study of the Efficacy and Safety of Lenalidomide, Subcutaneous Bortezomib and Dexamethasone (RVD) Combination Therapy for Patients with Newly Diagnosed Multiple Myeloma: Promising Activi…
http://www.bloodjournal.org/content/132/Suppl_1/1981

Nov 21st, 2018 – Introduction: Patients (pts) with newly diagnosed multiple myeloma (MM) are commonly treated with the standard of care combination of lenalidomide (Len), bortezomib (Bz), and dexamethasone (Dex), also known as RVD. A recent randomized phase 3 study found that the addition of Bz to Len and Dex significantly increased median overall and progression free survival as well as response rate (Durie et…

A Rapid Functional Screen for Small Molecule and Monoclonal Antibody Drug Sensitivity in Multiple Myeloma Patients
http://www.bloodjournal.org/content/132/Suppl_1/3203

Nov 21st, 2018 – Background: The oncogenic drivers and progression factors in multiple myeloma (MM) are heterogeneous and difficult to target therapeutically. As a result, personalized medicine approaches have not yet been realized. However, clinical availability of numerous anti-myeloma drugs and readily obtainable bone marrow (BM) aspirates raises the possibility to benefit patients by profiling the drug sens…

A Role for Syntenin-1 in Multiple Myeloma Cell Survival
http://www.bloodjournal.org/content/132/Suppl_1/1008

Nov 21st, 2018 – Multiple myeloma is the second most common hematological malignancy in the U.S. with an estimated 30,700 new diagnoses in 2018. It is a clonal disease of plasma cells that, despite recent therapeutic advances, remains incurable. Myeloma cells retain numerous characteristics of normal plasma cells including reliance on survival signals in the bone marrow for long term viability. However, maligna…

A Single-Cell Transcriptional Analysis of Tumour Cells and the Immune Microenvironment during Disease Evolution in a Transgenic Mouse Model of Myeloma
http://www.bloodjournal.org/content/132/Suppl_1/56

Nov 21st, 2018 – Introduction: Multiple Myeloma (MM) is consistently preceded by pre-malignant asymptomatic monoclonal gammopathies (AMG). To date, our understanding of the pathogenesis of progression to MM remains incomplete. Genetic analyses of AMG cells compared to MM-derived plasma cells (PCs) have found few differences, suggesting that progression may be mediated in part by tumour-extrinsic mechanisms. To …

Carfilzomib-Lenalidomide-Dexamethasone Versus Bortezomib-Lenalidomide-Dexamethasone in Patients with Newly Diagnosed Multiple Myeloma: Results from the Prospective, Longitudinal, Observational Comm…
http://www.bloodjournal.org/content/132/Suppl_1/799

Nov 21st, 2018 – Introduction: Triplet regimens incorporating a proteasome inhibitor and immunomodulatory drug are standards of care for the treatment of patients with newly diagnosed multiple myeloma (NDMM). The combinations of carfilzomib-lenalidomide-dexamethasone (KRd) and bortezomib-lenalidomide-dexamethasone (VRd) are recommended regimens for the treatment of NDMM by the National Comprehensive Care Networ…

Long-Lasting Remissions for Myeloma Patients on Daratumumab Therapy from the GEN501 and GEN503 Trials
http://www.bloodjournal.org/content/132/Suppl_1/3308

Nov 21st, 2018 – Introduction The first two trials to test the activity of daratumumab (DARA) in relapsed/refractory multiple myeloma (MM) were GEN501 (DARA monotherapy) and GEN503 (DARA in combination with lenalidomide [LEN] and dexamethasone [DEX]). GEN501 enrolled 104 participants from 2008 and GEN503 enrolled 45 participants from 2012. GEN501 has been completed; GEN503 is active but has finished accrual. We…

Activating KRAS, NRAS, and BRAF Mutants Enhance Proteasome Capacity and Reduce Endoplasmic Reticulum Stress in Multiple Myeloma, Thereby Promoting Plasma Cell Survival and Proteasome Inhibitor Resi…
http://www.bloodjournal.org/content/132/Suppl_1/406

Nov 21st, 2018 – Introduction: Multiple myeloma, a malignant proliferation of differentiated plasma cells, is the second most commonly diagnosed hematologic malignancy, and the number of cases may grow by almost 60% between 2010 and 2030. Recent therapeutic advances, including the use of proteasome inhibitors (PIs), have contributed to a doubling of the median overall survival in myeloma patients. This has been…

Long-Term Follow-up Identifies Double Hit and Key Mutations As Impacting Progression Free and Overall Survival in Multiple Myeloma
http://www.bloodjournal.org/content/132/Suppl_1/110

Nov 21st, 2018 – Introduction: The study of multiple myeloma (MM) genomics has identified many abnormalities that are associated with poor progression free survival (PFS) and overall survival (OS). Copy number abnormalities have been extensively studied in many datasets with long follow-up, however, the prognostic impact of mutations have not been extensively studied and available datasets have generally had a …

Addition of Ixazomib to an Rd Backbone Improves Clinical Benefit in Relapsed/Refractory Multiple Myeloma (RRMM) Patients (Pts) with Non-Canonical NF-KB Activation — Results from the Tourmaline-MM1 …
http://www.bloodjournal.org/content/132/Suppl_1/473

Nov 21st, 2018 – Background Ixazomib, the first oral proteasome inhibitor, is approved in combination with lenalidomide-dexamethasone (Rd) for pts with MM who have received at least 1 prior therapy. Approval was based on the phase 3 TOURMALINE-MM1 study (NCT01564537), in which ixazomib showed a consistent progression-free survival (PFS) benefit in combination with Rd (IRd) in the ITT population as well as in pr…

Long-Term Survivorship with Active Multiple Myeloma
http://www.bloodjournal.org/content/132/Suppl_1/1912

Nov 21st, 2018 – Background The survival of patients with multiple myeloma (MM) has improved significantly over the past two decades with the introduction of novel treatment agents. However, MM is still largely considered an incurable malignancy with a relapsing-remitting course. A follow-up of at least 10 years from active disease is required to determine whether a plateau in progression-free survival has been…

CD38 Specific Chimeric Antigen Receptor KHYG-1 Natural Killer Cells: A Potential "Off the Shelf" Therapy for Multiple Myeloma
http://www.bloodjournal.org/content/132/Suppl_1/3261

Nov 21st, 2018 – Chimeric Antigen Receptors (CARs) are engineered transmembrane proteins consisting of an antibody-derived antigen recognition domain linked to intracellular cell signaling domains. CAR engineered autologous T cells have been successful in the treatment of a variety of hematologic malignancies. However, several major caveats, including lack of universal donors, long manufacturing times, and abse…

AL Amyloidosis — Pathogenesis and Prognosis Are Determined By the Amyloidogenic Potential of the Light Chain and the Molecular Characteristics of Malignant Plasma Cells
http://www.bloodjournal.org/content/132/Suppl_1/187

Nov 21st, 2018 – INTRODUCTION. Systemic light chain amyloidosis (AL) is caused by accumulation of plasma cells producing misfolded monoclonal light chains depositing as amyloid fibrils in different organs, most frequently heart and kidney. AIM of our study is first assessing the molecular characteristics of malignant plasma cells from AL-patients in relation to those from MGUS, asymptomatic, and symptomatic mye…

CD38-Deficient, CD16-Engineered NK Cells Exhibit Enhanced Antibody-Dependent Cellular Cytotoxicity without NK Cell Fratricide to Augment Anti-Myeloma Immunity in Combination with Daratumumab
http://www.bloodjournal.org/content/132/Suppl_1/3224

Nov 21st, 2018 – Daratumumab targets the cell surface protein CD38 and is the only FDA approved monoclonal antibody that has demonstrated single agent efficacy in relapsed refractory myeloma. CD38 is broadly expressed in the immune system, and its high expression on multiple myeloma cells allows for effective targeting by daratumumab. Daratumumab induces myeloma cell death through multiple mechanisms, including…

Evaluation of Re-Intensification of Daratumumab to Weekly or Biweekly Dosing Schedule
http://www.bloodjournal.org/content/132/Suppl_1/2024

Nov 21st, 2018 – Introduction: Multiple Myeloma (MM) is a hematologic cancer caused by malignant plasma cells. Daratumumab is an immunoglobin G1 kappa human monoclonal antibody that targets CD38 antigen which is a cell surface glycoprotein highly expressed on myeloma cells. Daratumumab is FDA approved as monotherapy and in combination with dexamethasone and lenalidomide, bortezomib or pomalidomide in relapsed/r…

Lyra: A Phase 2 Study of Daratumumab (Dara) Plus Cyclophosphamide, Bortezomib, and Dexamethasone (Cybord) in Newly Diagnosed and Relapsed Patients (Pts) with Multiple Myeloma (MM)
http://www.bloodjournal.org/content/132/Suppl_1/152

Nov 21st, 2018 – Background: Dara, a human IgGκ monoclonal antibody that targets CD38, is approved in combination with bortezomib, melphalan, and prednisone (VMP) for the treatment of newly diagnosed (ND) MM. CyBorD is another commonly used immunomodulatory drug-sparing regimen for MM. We evaluated the safety and efficacy of dara-CyBorD and administered the first dara infusion as a split dose over 2 days in pts…

Altering Glycosphingolipid Composition to Improve Multiple Myeloma Bone Complication
http://www.bloodjournal.org/content/132/Suppl_1/1942

Nov 21st, 2018 – Multiple myeloma (MM) is an incurable cancer of plasma cells (PC), with a median survival of 5-7 years. Osteolytic bone disease and skeletal complications occur in more than 80% of MM patients and significantly contribute to the morbidity and mortality of these patients. Glycosphingolipid (GSL), an essential constituent of the outer leaflet of the cellular membrane, is altered in MM and other h…

Evaluation of the Revised International Staging System in 400 Patients with Symptomatic Myeloma in a Japanese Clinical Setting
http://www.bloodjournal.org/content/132/Suppl_1/4477

Nov 21st, 2018 – Background:In 2015, the International Myeloma Working Group (IMWG) developed the Revised International Staging System (R-ISS), which combined the ISS with the status of high-risk cytogenetic abnormalities (CAs) and serum levels of lactate dehydrogenase to identify three multiple myeloma (MM) entities with clearly different outcomes. However, although MM tends to affect older adults, the origina…

An Acquired High-Risk Chromosome Instability Phenotype in Multiple Myeloma: Jumping 1q Syndrome
http://www.bloodjournal.org/content/132/Suppl_1/4489

Nov 21st, 2018 – Introduction Chromosome instability (CIN) is a driver of copy number aberrations (CNAs) in cancer, and is a major factor leading to tumor heterogeneity and resistance to therapy. By definition, CIN is an increased rate or ongoing acquisition and accumulation of CNAs and not simply the existence of structurally and numerically abnormal aneuploid clones. In multiple myeloma (MM), the most common …

Maintenance with Carfilzomib Following Carfilzomib, Cyclophosphamide and Dexamethasone at First Relapse or Primary Refractory Multiple Myeloma (MM) on the Phase 2 Muk Five Study: Effect on Minimal …
http://www.bloodjournal.org/content/132/Suppl_1/802

Nov 21st, 2018 – Background The benefit of single agent maintenance is largely established from studies in newly diagnosed patients, while extended therapy combination regimens are more commonly used in relapsed disease. Extended therapy on combination protocols may be limited by tolerability and safety, as well as patient compliance. Fixed duration combination treatment followed by single agent maintenance may…

Characterising the Immunological Microenvironment in Newly Diagnosed Multiple Myeloma Bone Marrow By Time of Flight Cytometry Reveals Abnormalities in Antigen Presenting and Effector Lymphocyte Pop…
http://www.bloodjournal.org/content/132/Suppl_1/58

Nov 21st, 2018 – Background Loss of immune surveillance is thought to contribute to disease progression and treatment resistance in a range of malignancies including multiple myeloma (MM). Understanding the degree and pattern of immunological abnormality present within the bone marrow microenvironment at the time of MM diagnosis is vital if we are to utilize emerging immunological therapeutic strategies success…

Analysis of the Multiple Myeloma HLA Peptidome Identifies a Naturally Presented Bcma-Derived Peptide As an Immunogenic T-Cell Epitope for Immunotherapeutic Approaches
http://www.bloodjournal.org/content/132/Suppl_1/3173

Nov 21st, 2018 – The B-cell maturation antigen (BCMA) is selectively expressed by cells of the B-lineage, including multiple myeloma (MM) cells, and constitutes a promising target for immunotherapeutic approaches. At present, BCMA is being evaluated as target for immunotherapeutic approaches, such as CAR T cells and bispecific antibodies, which have demonstrated promising results in phase I clinical trials. The…

APRIL Is Significantly Elevated at All Stages of Multiple Myeloma (MM) and Interferes with Anti-Bcma Monoclonal Antibody-Mediated Cytolysis, Supporting the Clinical Evaluation of Bion-1301 As a Nov…
http://www.bloodjournal.org/content/132/Suppl_1/3209

Nov 21st, 2018 – A proliferation inducing ligand (APRIL) is a natural ligand with higher affinity than BAFF for both B cell maturation antigen (BCMA) and transmembrane activator and CAML interactor (TACI), which are overexpressed on multiple myeloma (MM) cells. APRIL, which is abundantly secreted by myeloma-supporting osteoclasts and macrophages, promotes MM cell progression in vivo and further induces regulato…

Maximizing Pre-Transplant Response Is Associated with Improved Outcome for Myeloma Patients: Exploratory Analysis of the Myeloma XI Trial
http://www.bloodjournal.org/content/132/Suppl_1/3280

Nov 21st, 2018 – Background: The depth of response both pre- and post- autologous stem cell transplant (ASCT) has been shown to correlate with clinical outcome for myeloma patients. Maximizing response can be achieved by modifying therapy either at induction, transplant, consolidation or during maintenance. In this work we explore the role of pre-transplant induction therapy in the UK NCRI Myeloma XI clinical t…

MCL-1 Inhibition Is Highly Effective Against Multiple Myeloma Cells from Poor Prognosis Patients
http://www.bloodjournal.org/content/132/Suppl_1/1916

Nov 21st, 2018 – Introduction: Despite recent advances in treatment, multiple myeloma (MM) is still considered incurable. Several novel therapies with different mechanisms of action are currently being studied for use in MM. These include targeted therapies such as pathway inhibitors and BCL-2 homology domain 3 (BH3) mimetics. BH3-mimetics overcome apoptosis resistance by binding and inhibiting select pro-survi…

MCRN¯003/MYX·1: A Single Arm Phase II Study of High-Dose Weekly Carfilzomib Plus Cyclophosphamide and Dexamethasone in the Treatment of Relapsed Multiple Myeloma after 1-3 Prior Therapies
http://www.bloodjournal.org/content/132/Suppl_1/1984

Nov 21st, 2018 – Background: Carfilzomib, a second generation proteosome inhibitor, is effective in the treatment of relapsed and refractory multiple myeloma (RRMM). Recent phase II and phase III trials have demonstrated the efficacy of weekly dosing strategies. The aim of this study was to examine high dose once weekly carfilzomib in combination with weekly dexamethasone and low dose weekly cyclophosphamide (w…

FDA Analysis of Outcomes in Older Adults with Relapsed or Refractory Multiple Myeloma
http://www.bloodjournal.org/content/132/Suppl_1/3287

Nov 21st, 2018 – Background: Multiple myeloma (MM) is a disease of older adults with a median age of onset of 70 years. Approximately 20% of the incident cases are diagnosed in patients 85 years and older. There is significant heterogeneity among older adults with regards to the tolerability of myeloma directed therapy. In newly diagnosed transplant ineligible patients with MM, available evidence indicates that…

Baseline and on-Treatment Bone Marrow Microenvironments Predict Myeloma Patient Outcomes and Inform Potential Intervention Strategies
http://www.bloodjournal.org/content/132/Suppl_1/1882

Nov 21st, 2018 – Introduction The multiple myeloma (MM) tumor microenvironment (TME) strongly influences patient outcomes as evidenced by the success of immunomodulatory therapies. To develop precision immunotherapeutic approaches, it is essential to identify and enumerate TME cell types and understand their dynamics. Methods We estimated the population of immune and other non-tumor cell types during the course…

Clinical Responses and Pharmacokinetics of MCARH171, a Human-Derived Bcma Targeted CAR T Cell Therapy in Relapsed/Refractory Multiple Myeloma: Final Results of a Phase I Clinical Trial
http://www.bloodjournal.org/content/132/Suppl_1/959

Nov 21st, 2018 – Introduction: BCMA targeted CAR T cell therapy has shown promising results in patients with relapsed/refractory multiple myeloma (MM). Herein, we report on the safety and efficacy of MCARH171, a second generation, human derived BCMA targeted autologous 4-1BB containing CAR T cell therapy, including a truncated epidermal growth factor receptor safety system (Smith EL. Mol Ther 2018). Methods: Th…

Metabolomic Profiling of Serum from Myeloma and MGUS Patients – a Novel Strategy to Identify Potential Biomarkers of Myeloma Development and Progression
http://www.bloodjournal.org/content/132/Suppl_1/1891

Nov 21st, 2018 – Introduction: Drivers that underlie the progression of MGUS (Monoclonal gammopathy of undetermined significance) to multiple myeloma are yet largely unknown. Because of the vast number of potential players, these drivers may not necessarily aimed to transform plasma cell or the bone marrow niche, but rather remodel a supporting microenvironment. Metabolic alterations have been linked to cancer …

Fully Human Bcma Targeted Chimeric Antigen Receptor T Cells Administered in a Defined Composition Demonstrate Potency at Low Doses in Advanced Stage High Risk Multiple Myeloma
http://www.bloodjournal.org/content/132/Suppl_1/1011

Nov 21st, 2018 – Background: Despite advances in the treatment of multiple myeloma (MM) almost all patients relapse and high risk features continue to portend a short median survival. The adoptive transfer of B-Cell Maturation Antigen (BCMA) chimeric antigen receptor (CAR) T cells is demonstrating early promise in MM, but the durability of response has not been established. The infusion of genetically modified …

Functional Analysis of HDAC11 in Plasma Cell Development and Multiple Myeloma Survival
http://www.bloodjournal.org/content/132/Suppl_1/3223

Nov 21st, 2018 – Background: Histone deacetylases (HDACs) are potential novel therapeutic targets for multiple myeloma (MM) treatment. A pan-HDAC inhibitor (HDI) panobinostat was approved by the FDA in 2015 to treat relapsed/refractory MM patients, and several other HDIs are currently in different phases of clinical trials. However, unfavorable side-effects of the non-selective HDIs necessitate further dissecti…

Minimal Residual Disease (MRD) Analysis Using Multiparametric Flow Cytometry (MFC) and Identification of Differences in Subpopulations Using Next Generation Sequencing (NGS) in the Bone Marrow (BM)…
http://www.bloodjournal.org/content/132/Suppl_1/3222

Nov 21st, 2018 – Introduction: MM is characterized by the accumulation of aberrant BM plasma cells (aPCs). The use of novel agents for anti-MM treatment has enabled the achievement of deeper responses and prolonged progression free survival (PFS) and overall survival (OS). These advances have created the need for sensitive means to detect residual PCs. MFC allows aPC detection with high sensitivity and is used …

Functional Cure, Defined As PFS of More Than 7 Years, Is Achieved in 9% of Myeloma Patients in the Era of Conventional Chemotherapy and of First-Generation Novel Anti-Myeloma Agents; A Single-Cente…
http://www.bloodjournal.org/content/132/Suppl_1/1968

Nov 21st, 2018 – Advances in the management of multiple myeloma (MM) led to a significant prolongation of overall survival (OS), mainly of the younger patients; almost 10% of them experience more than 10-year OS. Although long progression-free survival (PFS) correlates with extended OS, there is very limited information for the characteristics of patients who manage to be progression-free for a long period afte…

Molecular Characterization By Immune Profiling of Paired Blood and Bone Marrow in Multiple Myeloma and Its Precursor States
http://www.bloodjournal.org/content/132/Suppl_1/4461

Nov 21st, 2018 – INTRODUCTION: Progression from precursor states, MGUS and smoldering multiple myeloma (SMM), to multiple myeloma (MM) is dependent upon adaptive and innate immune contexture shaped by cross-talk between malignant plasma cells and bone marrow (BM) milieu. The complexity and heterogeneity of interactions between the immune system and plasma cells in BM triggers alterations in peripheral blood (PB…

Preclinical Validation Studies Support Causal Machine Learning Based Identification of Novel Drug Targets for High-Risk Multiple Myeloma
http://www.bloodjournal.org/content/132/Suppl_1/3210

Nov 21st, 2018 – Introduction Regardless of significant advances in the therapy of multiple myeloma (MM) there is still a lack of effective treatment options for patients with high-risk disease. In this context, we recently developed a network of high-risk disease based on more than 30 000 genomic and clinical variables from 645 patients of the CoMMpass dataset (Gruber et al., ASH 2016). Validation of these fin…

Monoclonal Gammopathy of Undetermined Significance – Patient Characteristics and Referral Patterns
http://www.bloodjournal.org/content/132/Suppl_1/4496

Nov 21st, 2018 – Introduction Monoclonal gammopathy of undetermined significance (MGUS) is a prevalent hematological condition among elderly population with incidence rates of 3% and 5% over the age of 50 and 70 years, respectively (Kyle et al., 2018). It is considered a premalignant state of multiple myeloma with a risk of progression of 1% per year. It has also been shown that MGUS patients have a shorter sur…

Comprehensive Multi-Omics Analysis of Gene Fusions in a Large Multiple Myeloma Cohort
http://www.bloodjournal.org/content/132/Suppl_1/1898

Nov 21st, 2018 – Introduction: Gene fusions are the result of genomic rearrangements that create hybrid protein products or bring the regulatory elements of one gene into close proximity of another. Fusions often dysregulate gene function or expression through oncogene overexpression or tumor suppressor underexpression (Gao, Liang, Foltz, et al. Cell Rep 2018). Some fusions such as EML4–ALK in lung adenocarcin…

Genomic Abnormalities Among African Individuals with Monoclonal Gammopathies Using Calculated Ancestry
http://www.bloodjournal.org/content/132/Suppl_1/4458

Nov 21st, 2018 – Monoclonal gammopathies, including multiple myeloma (MM), represent a group of plasma cell (PC) disorders that comprise of mostly incurable hematopoietic malignancies with an increasing incidence in the US. Previous epidemiological studies demonstrated a 2-3 fold higher incidence of monoclonal gammopathy of undetermined significance (MGUS) and a similarly higher incidence of MM along with a ~4-…

Preliminary Analysis of the Australasian Leukaemia and Lymphoma Group (ALLG) MM17 Trial: Response Adaptive Salvage Treatment with Carfilzomib-Thalidomide-Dexamethasone (KTd) for Newly Diagnosed Tra…
http://www.bloodjournal.org/content/132/Suppl_1/3279

Nov 21st, 2018 – Background Data from the Australian and New Zealand (ANZ) Myeloma and Related Diseases Registry (MRDR) shows that 85% of newly diagnosed multiple myeloma (NDMM) patients (pts) in ANZ are induced with bortezomib(V)-containing therapies, predominantly triplets of V-cyclophosphamide-dexamethasone (VCD). Of these, 15% demonstrate treatment failure – either a sub-optimal response (

CRISPR Activation Screen for Drivers of MM Cell Proliferation
http://www.bloodjournal.org/content/132/Suppl_1/3197

Nov 21st, 2018 – CRISPR/Cas9-based gene editing has become a powerful tool for loss-of-function (LOF) studies and has allowed us to systematically interrogate the function of genes regulating the survival and proliferation of multiple myeloma (MM) cells in vitro, in vivo and in the context of treatment resistance (e.g. De Matos Simoes et al., Shirasaki et al., and Gandolfi et al. ASH 2017). We reasoned, however…

Preliminary Results from a Phase I Study of Isatuximab (ISA) in Combination with Bortezomib, Lenalidomide, Dexamethasone (VRd), and in Patients with Newly Diagnosed Multiple Myeloma (NDMM) Non-Elig…
http://www.bloodjournal.org/content/132/Suppl_1/595

Nov 21st, 2018 – Background: Isatuximab (ISA) is an anti-CD38 monoclonal antibody with multiple modes of action for killing tumor cells via direct tumor targeting and immune cell engagement. ISA, combined with bortezomib, has demonstrated strong potentiation in a multiple myeloma (MM) xenograft model (Clin Cancer Res 2014:20:4754). This supported evaluation of ISA with bortezomib combinations in pts with newly …

Multidimensional Immunophenotyping Identifies Hallmarks of Systemic Light-Chain Amyloidosis (AL) and Maps the Disease in the Crossroad between MGUS and Multiple Myeloma (MM)
http://www.bloodjournal.org/content/132/Suppl_1/3170

Nov 21st, 2018 – Background: Since survival in AL mainly depends on the extent of organ involvement of patients at presentation, early diagnosis and risk stratification are key to improve patients’ outcome. Therefore, together with surrogates of organ involvement, biomarkers identifying patients with MGUS or MM at greater risk of developing AL would be highly valuable to prevent organ damage, to maximize therap…

CRISPR-Cas9 Mediated CD45 Knockout Inactivates Src Family Kinases and Impairs Cell Migration in Multiple Myeloma
http://www.bloodjournal.org/content/132/Suppl_1/1907

Nov 21st, 2018 – Introduction Multiple myeloma (MM) is a plasma cell malignancy that manifests continuous cell dissemination to multiple bone marrow (BM) niches and extramedullary (EM) sites. However, the molecular mechanisms behind this phenomenon remain elusive. CD45, a receptor tyrosine phosphatase, is an important regulator for T-cell and B-cell signaling pathways. In MM, the loss of CD45 expression has bee…

Global 3D-Epigenetic Dysregulation of Cyclin D1 and D2 Actively Controls Their Expression Pattern in Multiple Myeloma
http://www.bloodjournal.org/content/132/Suppl_1/3904

Nov 21st, 2018 – Introduction: Multiple myeloma (MM) is characterized by the over-expression of D-cyclin genes and the expression is tightly linked to cytogenetic subgroups. For instance, overexpression of CCND1 in the t(11;14) and CCND3 in the t(6;14) is direct through IgH super-enhancer translocation, and CCND2 overexpression in t(4;14), t(14;16) and t(14;20) indirectly, presumably as a result of transcriptio…

Critical Role for Apobec and Its Interacting Partners in Mediating Mutations and Cell Growth in Multiple Myeloma (MM)
http://www.bloodjournal.org/content/132/Suppl_1/4462

Nov 21st, 2018 – The APOBEC family of cytidine deaminases include AID (activity induced deaminase) and 10 related APOBEC enzymes (A1,A2,A3A,A3B,A3C,A3D,A3F,A3G,A3H and A4). AID is well studied for its role in somatic hyper mutation and class switch recombination of immunoglobulin genes. APOBECs (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) have been shown to have roles in mRNA editing and i…

Graded Cardiac Response Correlates with Relapse and Survival in AL Amyloidosis
http://www.bloodjournal.org/content/132/Suppl_1/4486

Nov 21st, 2018 – Seventy percent of all patients with light chain amyloidosis (AL) have cardiac involvement, and most of those patients ultimately die from complications related to their heart disease. While consensus guidelines outline criteria for grading hematologic response to chemotherapy for AL, there are no currently validated criteria for grading cardiac response to therapy. Recently, Muchtar et al. cre…

Cybord-Dara Is a Highly Effective Upfront Treatment for Newly Diagnosed Multiple Myeloma. Initial Efficacy Results of the 16-Bcni-001/Ctrial-IE (ICORG) 16-02 Study
http://www.bloodjournal.org/content/132/Suppl_1/3242

Nov 21st, 2018 – Introduction: Daratumumab (DARA), a human IgG1k monoclonal antibody with single activity in multiple myeloma (MM) shows strong synergy in combination with other anti-MM agents, including immunomodulatory drug (IMiDs) and proteasome inhibitors (PI). This has led to the exploration of DARA in combination with front line regimens. Triplets including a PI and an IMiD are considered an ideal backbon…

HDP101, a Novel B-Cell Maturation Antigen (BCMA)-Targeted Antibody Conjugated to α-Amanitin, Is Active Against Myeloma with Preferential Efficacy Against Pre-Clinical Models of Deletion 17p
http://www.bloodjournal.org/content/132/Suppl_1/593

Nov 21st, 2018 – Background: Deletion (del) of 17p involving the p53 tumor suppressor (TP53) remains an adverse prognostic factor in multiple myeloma (MM) despite the use of novel agents as well as high-dose chemotherapy with autologous stem cell rescue. Genomic TP53 deletion can cause haploinsufficiency of nearby genes, such as RNA polymerase II subunit A (POLR2A), which ia also located on 17p13.1. We therefor…

Cyclophosphamide, Pomalidomide and Dexamethasone Significantly Improves Response over Poma/Dex in Relapsed/Refractory Myeloma Patients Previously Treated with Cyclophosphamide Combination Therapy -…
http://www.bloodjournal.org/content/132/Suppl_1/3274

Nov 21st, 2018 – Background and aims Treatment of relapsed/refractory myeloma (RRMM) remains a challenge as most approved and commonly accessible doublet treatments induce responses (≥PR) in less than half of patients. The combination of the classical alkylator cyclophosphamide with thalidomide (CTD) or lenalidomide (CRD) is standard of care in early lines of therapy in the UK and elsewhere. Data on the clinica…

Myeloma Patient-Derived MCL1 Point Mutations Can Influence MCL1-Inhibitor Function
http://www.bloodjournal.org/content/132/Suppl_1/951

Nov 21st, 2018 – Multiple myeloma is a malignancy of long-lived plasma cells of the bone marrow that is rarely curable. Thus, despite recent advances in the development of new therapies, additional approaches are required. We investigated potential molecular vulnerabilities in the BCL2 family. Using the MMRF CoMMpass (NCT0145429) study (IA13), we determined the frequency of nonsynonymous coding mutations in the…

Hematogenous Extramedullary Relapse in Multiple Myeloma – A Multicenter Retrospective Study in 127 Patients
http://www.bloodjournal.org/content/132/Suppl_1/2004

Nov 21st, 2018 – Background: Hematogenous extramedullary multiple myeloma (HEMM), though rare, is mainly observed in MM patients at relapse. The current study assesses the characteristics and outcomes of patients with MM who develop HEMM in the novel agent era. Methods: Consecutive patients, treated in 16 participating centers and diagnosed with HEMM, were included. Patient characteristics at diagnosis and at H…

Deciphering Clonal Evolution and Dissemination of Multiple Myeloma Cells In Vivo
http://www.bloodjournal.org/content/132/Suppl_1/55

Nov 21st, 2018 – Introduction: Multiple Myeloma (MM) is a genetically complex and evolutionary process with well defined precursor states, which offer a unique opportunity to study the sequential evolution of the disease. A small number of detectable pre-malignant clones are present in early stage and continue to acquire more genomic abnormalities leading to overt disease. The interaction between cancer cells a…

Progression Free Survival below 12 Months Following Stem Cell Transplant Is a Hallmark of High-Risk Myeloma Which Is Associated with Inferior Overall Survival — Data from the Ukmrc Myeloma XI Trial
http://www.bloodjournal.org/content/132/Suppl_1/122

Nov 21st, 2018 – Introduction Multi-agent induction chemotherapy followed by autologous stem cell transplant (ASCT) is a standard of care for younger patients with multiple myeloma, aimed at maximising the depth and duration of first response (PFS1). However, the duration of PFS1 is variable between patients. Improved understanding of how to identify high risk patients who relapse early and the ability to desig…

High Levels of APOBEC3B Gene Expression Contribute to Poor Prognosis in Multiple Myeloma Patients
http://www.bloodjournal.org/content/132/Suppl_1/3897

Nov 21st, 2018 – Introduction: Poor prognosis and drug resistance in multiple myeloma (MM) is associated with increased mutational load. APOBEC3B is a major contributor to mutagenesis, especially in myeloma patients with t(14;16) MAF subgroup. It was shown recently that presence of the APOBEC signature at diagnosis is an independent prognostic factor for progression free survival (PFS) and overall survival (OS)…

Deep Immunoprofiling of the Bone Marrow Microenvironmental Changes Underlying the Multistep Progression of Multiple Myeloma
http://www.bloodjournal.org/content/132/Suppl_1/243

Nov 21st, 2018 – Introduction The multistep progression of multiple myeloma from a normal plasma cell to a system with the features of invasive cancer provides a unique opportunity to understand the co-evolution of the malignant clone within its microenvironment. Understanding these changes is becoming increasingly important as we attempt to design early intervention strategies and to precisely leverage emergin…

Proliferation and Molecular Risk Score of Low Risk Myeloma Cells Are Increased in High Risk Microenvironment Via Augmented Bioavailability of Growth Factors
http://www.bloodjournal.org/content/132/Suppl_1/1929

Nov 21st, 2018 – Introduction: Multiple myeloma (MM) cells from patients with smoldering MM (SMM) and low-risk (LR) MM harbor genetic alterations typically seen in patients with high-risk (HR) disease. To test whether the bone marrow (BM) microenvironment plays a role in controlling growth of LR MM cells, we established an experimental model that mimics a HR microenvironment by co-culturing normal mesenchymal s…

Next-Generation Sequencing-Based Assay Shows High Clonal Characterization Success Rate for Plasma Cell Neoplasms, and Concordance with Flow Cytometry in Minimal Residual Disease Detection
http://www.bloodjournal.org/content/132/Suppl_1/4475

Nov 21st, 2018 – Introduction After therapy or stem cell transplantation, multiple myeloma patients achieving complete response (CR) or stringent complete response (sCR) can still have a significant risk of disease relapse, illustrating the importance of using highly sensitive methods for minimal residual disease (MRD) detection and prognostication. Two techniques used clinically for MRD detection include multi…

Development and Evaluation of CART Targeting Bcma with Humanized Alpaca-Derived Single-Domain Antibody As Antigen Recognition Domain
http://www.bloodjournal.org/content/132/Suppl_1/1976

Nov 21st, 2018 – Chimeric antigen receptor T cells (CART) targeting CD19 have shown substantial activity against leukemia and lymphoma, which motivated developing CART cell therapy for Multiple myeloma (MM). B cell maturation antigen (BCMA) is the target molecule in MM. Several kinds of CART targeting BCMA have been created from 2016. Among these, the Bluebird Bio uses the humanized murine BCMA scFv to make CAR…

Identification of Specificity Groups in Myeloma Patients T Cell Receptor (TCR) Repertoire through Single Cell TCR Sequencing
http://www.bloodjournal.org/content/132/Suppl_1/4459

Nov 21st, 2018 – Background: A renewed interest in immune and cellular based therapeutics in multiple myeloma was recently fueled by the development of CD38 targeting monoclonal antibodies as well as the introduction of engineered CAR-T cells. Daratumumab treatment in myeloma patients was demonstrated to expand clonal CD8+T cells and T cell clonality was correlated with the depth of response consistent with a d…

Novel Combination Therapy Targeting rDNA Transcription and Histone Deacetylation Provides Effective Treatment for Multiple Myeloma, and Synergises in Bortezomib-Resistant MM
http://www.bloodjournal.org/content/132/Suppl_1/1945

Nov 21st, 2018 – Background: Multiple myeloma (MM) requires combination drug therapies to delay acquired drug resistance and clinical relapse. We co-developed CX-5461, a highly-selective inhibitor of RNA polymerase I-mediated rDNA transcription(1), currently in phase I trials for relapsed haematological malignancies (Peter Mac). CX-5461 produces a targeted nucleolar DNA damage response (DDR), triggering both a …

Quantitative Integrative Prediction of Survival Probability in Multiple Myeloma Using Molecular and Clinical Prognostic Factors in 657 Patients Treated with Bortezomib-Based Induction, High-Dose Th…
http://www.bloodjournal.org/content/132/Suppl_1/403

Nov 21st, 2018 – Background Survival in multiple myeloma ranges from months to decades and the majority of patients remain incurable with current treatment approaches. Given this high variability, it would be clinically very useful to quantitatively predict survival on a continuous scale. Current risk prediction models attribute patients to 2-3 groups, i.e. high, intermediate, and low risk. Group size and survi…

Immune Mediated Mechanisms of Resistance to Daratumumab
http://www.bloodjournal.org/content/132/Suppl_1/3201

Nov 21st, 2018 – Introduction: Daratumumab (Dara) is a human monoclonal antibody targeting the highly expressed multiple myeloma (MM) surface receptor CD38, with significant activity in relapsed MM. However, resistance to Dara develops in virtually all patients (pts). Thus, in order to maximize its clinical activity and prevent resistance, it is imperative to understand why pts stop responding. Our group recent…

Real World Analysis of the Incidence and Impact of Hypertension and Cardiac Toxicity Associated with Carfilzomib for Patients with Multiple Myeloma
http://www.bloodjournal.org/content/132/Suppl_1/3255

Nov 21st, 2018 – Background: Carfilzomib (CFZ) is a potent, irreversible proteasome inhibitor (PI) licenced in patients with multiple myeloma (MM) demonstrating improved progression free and overall survival (OS) to standard of care therapies. However, CFZ is also associated with hypertension (HTN) and rarely cardiac toxicity. The exact mechanism is unclear but may be due to a disturbance of endothelial nitric …

Real World Data on the Efficacy and Safety of Daratumumab in Relapsed/Refractory Multiple Myeloma: Data Collected from the Hungarian Hematology Centers
http://www.bloodjournal.org/content/132/Suppl_1/3257

Nov 21st, 2018 – Background: Daratumumab is one of the most effective new myeloma drugs recently approved for relapsed/refractory multiple myeloma (MM), first in monotherapy in heavily pretreated patients, later in triplet combinations from first relapse, based on the results of the SIRIUS, POLLUX and CASTOR trials that showed good tolerability and high effectivity of daratumumab both in monotherapy and combine…

Durable Remission Achieved from Bcma-Directed CAR-T Therapy Against Relapsed or Refractory Multiple Myeloma
http://www.bloodjournal.org/content/132/Suppl_1/956

Nov 21st, 2018 – Background: Promising results are seen from several early phase clinical trials on the cellular immunotherapy based on chimeric antigen receptor (CAR)-engineered T (CAR-T) targeting B cell maturation antigen (BCMA) for the treatment of relapsed/refractory (RR) multiple myeloma (MM). We developed an anti-BCMA CAR-T cell product manufactured via gamma-retrovirus-mediated transduction of activated…

Immunoglobulin Lambda Translocations Identify Poor Outcome and IMiD Resistance in Multiple Myeloma and Co-Occur with Hyperdiploidy
http://www.bloodjournal.org/content/132/Suppl_1/405

Nov 21st, 2018 – Patients with the plasma cell malignancy multiple myeloma now benefit from treatments such as proteasome inhibitors, immunomodulatory imide drugs (IMiDs), autologous stem cell transplant, and monoclonal antibodies. However, 20% of patients still relapse or die within two years and are deemed ‘high risk’. Current markers fail to identify all high-risk patients resulting in misdiagnoses, therefor…

Real-World Outcomes with Bortezomib-Containing Regimens and Lenalidomide Plus Dexamethasone for the Treatment of Transplant Ineligible MM Patients: A Multi-Institutional Report from the National My…
http://www.bloodjournal.org/content/132/Suppl_1/2008

Nov 21st, 2018 – Introduction: Bortezomib-containing regimens (BCRs) have been the standard frontline approach for the treatment of transplant ineligible multiple myeloma (TIMM) patients in Canada for many years. Based on recent randomized clinical trial results lenalidomide and dexamethasone (Ld) has become another provincially funded option in Canada in the same therapeutic space. We aimed to compare the effe…

Outcome of Soft-Tissue Plasmocytomas in Newly Diagnosed Multiple Myeloma Patients Treated with New Drugs
http://www.bloodjournal.org/content/132/Suppl_1/3235

Nov 21st, 2018 – Introduction Multiple myeloma (MM) can be associated with paraskeletal (PP) or extramedullary (EMP) plasmocytomas (PL). Although PLs are relatively frequent, even at diagnosis, our knowledge on the subject mainly relies on small case series or single center experiences. Remarkably, little is known regarding the role of new drugs on MM with PL. Aim To perform a meta-analysis of 8 EMN-GIMEMA stud…

E2F1 Is a Biomarker of Selinexor Resistance in Relapsed/Refractory Multiple Myeloma Patients
http://www.bloodjournal.org/content/132/Suppl_1/3216

Nov 21st, 2018 – Selinexor (KPT-330) is a selective inhibitor of nuclear export (SINE) which specifically targets XPO1 (Exportin 1)-mediated nuclear export, leading to increased nuclear retention of major tumor suppressor proteins and inducing selective apoptosis in cancer cells. Several phase I and II clinical trials demonstrate evidence of anti-cancer activity of Selinexor in solid tumors (i.e metastatic pros…

Outcomes of Black Patients with Multiple Myeloma in the Veterans Health Administration
http://www.bloodjournal.org/content/132/Suppl_1/840

Nov 21st, 2018 – Background: Multiple myeloma (MM) is the most common hematologic malignancy in blacks with more than twice the incidence of non-black populations in national registry data. Prior studies have shown that blacks present with MM at an earlier age and have improved survival compared to non-blacks, contrary to the pattern in most malignancies. These findings have been theorized due to the effects of…

Early Serum Free Light Chain (SFLC) Kinetics Is Highly Predictive of Renal Response in Carfilzomib/ Dexamethasone (Cfz/Dex) in Myeloma (MM) Patients with Renal Impairment (RI) — Interim Analysis of…
http://www.bloodjournal.org/content/132/Suppl_1/3283

Nov 21st, 2018 – BACKGROUND & METHODS Cfz/Dex is a standard of care in relapsed MM, and renal impairment is a poor prognostic factor. The ALLG MM16 trial was initiated to assess the feasibility of treating patients (pts) who have significant RI (eGFR 15 – 40 ml/min) with Cfz/Dex, and to determine whether an early reduction in serum free light chains (SFLC), with a short half-life, could predict renal outcome. A…

Impact of Early Progression on Long Term Outcomes Among Myeloma Patients Receiving Lenalidomide, Bortezomib, and Dexamethasone (RVD) Induction Therapy
http://www.bloodjournal.org/content/132/Suppl_1/3302

Nov 21st, 2018 – Background: The incorporation of modern day induction regimens, autotransplant and continuous maintenance has resulted in better long-term outcomes for myeloma patients. Experience and trials demonstrated that by prolonging 1st progression-free survival (PFS1) and pushing the relapse farther, we can gain the OS advantage (McCarthy et al NEJM 2012). Unfortunately, a subgroup of patients fail to …

Impact of HIV on Clinical Presentation and Outcomes of Individuals with Multiple Myeloma
http://www.bloodjournal.org/content/132/Suppl_1/3162

Nov 21st, 2018 – Introduction: HIV infection and the resulting immunodeficiency predispose individuals to various plasma cell disorders including reactive plasmacytosis, monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM) and plamacytomas. Studies have demonstrated nearly 4.5-fold increased risk of MM in HIV-infected (HIV+) individuals. Limited evidence from case reports/small serie…

Impact of Treatment on B-Cell Regeneration By Next Generation Flow Cytometry in Patients with Multiple Myeloma
http://www.bloodjournal.org/content/132/Suppl_1/4491

Nov 21st, 2018 – Introduction: Several studies have shown the role of the immune system in the development of MM, but there is no systematic description of normal B-cell regeneration during treatment points. Recently, EuroFlow consortium has developed NGF panel with high sensitivity to evaluated MRD and potentially, to assess of the normal B-cell compartment of patients with MM. Aims: Here we evaluated the B ce…

Effective Lipidoid Nanoparticle Delivery In Vivo of siRNA Targeting Kappa Light Chain Production in a Murine Xenograft Model
http://www.bloodjournal.org/content/132/Suppl_1/3208

Nov 21st, 2018 – INTRODUCTION: Despite advances in therapy, patients with relapsed AL amyloidosis die of resistant disease. New therapies are needed. siRNA directed at the constant regions of Ig light chains (LC) reduces LC mRNA and protein from patient cells, from human myeloma and AL cell lines, and in a flank plasmacytoma model with in vivo electroporation (Blood 2014;123:3440; Gene Ther 2016;23:727). To del…

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Journal de Pharmacie Clinique

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480
alsfakia

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JOURNAL DE PHARMACIE CLINIQUE
Volume 36, numéro 2, 2017
Retour sur la journée annuelle des internes en pharmacie

Cette 2è journée scientifique placée sous le thème de l’Économie de la santé : « Le prix du médicament en France : enjeux thérapeutiques contre enjeux économiques ? ».

Retrouvez l’article paru dans le Journal de Pharmacie CliniqueN°2-2017.

SOMMAIRE :
ÉDITORIAL
> L’importance du réseautage !
Aude Desnoyer, Aurélie Guérin, André Rieutord
SYNTHÈSES
> Formation et opportunités de carrières en pharmacie hospitalière : le point de vue de futurs et de jeunes diplômés du DES de pharmacie
Chloé Duran, Laura di Trapani, Christel Hosselet, Marie Lenski, Evariste Delande, Delphine Heurté, Alexandre Drezet, Jérémie Zerbit, Emmanuel Cirot, Clément Delage
> Comment le pharmacien peut-il prendre l’initiative pour coopérer avec les services cliniques ?
Marc Frachette, Véronique Zardet
> Votre temps-réponse est-il assez rapide ? Mise en œuvre d’un projet lean en pharmacie hospitalière afin de réduire le temps de préparation des ordonnances
Lise Vaillancourt, Mimi Truong
> Évaluation des technologies de santé en milieu hospitalier : organisations possibles et exemples appliqués aux dispositifs médicaux
Nicolas Martelli
> Accompagnement pharmaceutique du patient obèse à l’officine : état des lieux territorial
Audrey Decottignies, Sophie Renet, Sophie Cavalier, Guillaume Pourcher, André Rieutord
CONGRÈS
cadeau.jpg 2e Journée scientifique des internes en pharmacie d’Île-de-France
Aurélie Chaigneau, Rémi Pieragostini, Marie Cabagnols, Clément Delage
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