×
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 ...

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...