Circulating Soluble Urokinase-Type Plasminogen Activator Receptor Levels Reflect Renal Function in Newly Diagnosed Patients with Multiple Myeloma Treated with Bortezomib-Based Induction.

(1) Background: Soluble urokinase-type plasminogen activator receptor (suPAR) has been implicated in the pathogenesis of kidney disease in different disease settings. The aim of this study was to investigate a possible link between suPAR circulating levels and renal impairment (RI) in newly diagnosed patients with symptomatic multiple myeloma (NDMM) before and after frontline therapy with bortezomib-based regimens. (2) Methods: We studied 47 NDMM patients (57% males, median age 69.

Ixazomib as Postinduction Maintenance for Patients With Newly Diagnosed Multiple Myeloma Not Undergoing Autologous Stem Cell Transplantation: The Phase III TOURMALINE-MM4 Trial.

Purpose: Maintenance therapy prolongs progression-free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM) not undergoing autologous stem cell transplantation (ASCT) but has generally been limited to immunomodulatory agents. Other options that complement the induction regimen with favorable toxicity are needed.

Patients And Methods: The phase III, double-blind, placebo-controlled TOURMALINE-MM4 study randomly assigned (3:2) patients with NDMM not undergoing ASCT who achieved better than or equal to partial response after 6-12 months of standard induction therapy to receive the oral proteasome inhibitor (PI) ixazomib or placebo on days 1, 8, and 15 of 28-day cycles as maintenance for 24 months.

The Role of Low Dose Whole Body CT in the Detection of Progression of Patients with Smoldering Multiple Myeloma.

Multiple myeloma (MM) is the second most common hematological malignancy, characterized by plasma cell bone marrow infiltration and end-organ involvement. Smoldering MM (SMM) is an intermediate clinical entity between MGUS and MM, with a risk of progression to symptomatic disease 10% per year. Bone disease is the most frequent symptom of MM, with ~90% of patients developing bone lesions throughout their disease course.

Evaluation of Daratumumab for the Treatment of Multiple Myeloma in Patients With High-risk Cytogenetic Factors: A Systematic Review and Meta-analysis.

Importance: The addition of daratumumab to backbone multiple myeloma (MM) regimens is associated with improved response rates and progression-free survival (PFS). Whether improved outcomes are also associated with this regimen among patients with cytogenetically defined high-risk MM (HRMM) remains unclear.

Objective: To measure PFS associated with adding daratumumab to backbone MM regimens among patients with HRMM.

Guidance for the Management of Patients with Vascular Disease or Cardiovascular Risk Factors and COVID-19: Position Paper from VAS-European Independent Foundation in Angiology/Vascular Medicine.

COVID-19 is also manifested with hypercoagulability, pulmonary intravascular coagulation, microangiopathy, and venous thromboembolism (VTE) or arterial thrombosis. Predisposing risk factors to severe COVID-19 are male sex, underlying cardiovascular disease, or cardiovascular risk factors including noncontrolled diabetes mellitus or arterial hypertension, obesity, and advanced age. The VAS-European Independent Foundation in Angiology/Vascular Medicine draws attention to patients with vascular disease (VD) and presents an integral strategy for the management of patients with VD or cardiovascular risk factors (VD-CVR) and COVID-19.

Elotuzumab, lenalidomide, and dexamethasone in RRMM: final overall survival results from the phase 3 randomized ELOQUENT-2 study.

Prolonging overall survival (OS) remains an unmet need in relapsed or refractory multiple myeloma (RRMM). In ELOQUENT-2 (NCT01239797), elotuzumab plus lenalidomide/dexamethasone (ERd) significantly improved progression-free survival (PFS) versus lenalidomide/dexamethasone (Rd) in patients with RRMM and 1-3 prior lines of therapy (LoTs). We report results from the pre-planned final OS analysis after a minimum follow-up of 70.

Systemic AL Amyloidosis: Current Approaches to Diagnosis and Management.

AL amyloidosis is characterized by a low-level expansion of an indolent, small plasma cell clone that produces amyloidogenic light chains. Amyloid aggregates or preceding intermediaries cause direct cell damage through their proteotoxicity, and amyloid deposits distort tissue architecture, and, eventually, lead to organ impairment. It is a rare, underdiagnosed disease with a diverse clinical presentation depending on the organ tropism of the amyloid fibrils; cardiac and renal involvement is most common, but any organ can be affected, excluding the central nervous system.

Current trends in the management and prevention of human papillomavirus (HPV) infection.

Purpose: Herein, we critically evaluate and discuss current literature in the field of human papillomavirus (HPV) pathogenesis, treatment, and prevention.

Methods: Screening of the literature and selection of studies was performed until May 31st, 2019.

Results: HPV is considered the commonest heterosexual and homosexual sexually transmitted infection globally.

Daratumumab-based therapy for patients with monoclonal gammopathy of renal significance.

Treatment of the plasma cell clone in monoclonal gammopathy of renal significance (MGRS) is necessary in order to reduce toxic immunoglobulin load to the kidneys and salvage renal function. There are limited data on the use of daratumumab in patients with MGRS. We summarize our experience with the use of daratumumab-based therapy in 25 MGRS patients, 12 of whom were previously untreated.

Next generation flow cytometry for MRD detection in patients with AL amyloidosis.

The treatment of AL amyloidosis aims to eradicate the plasma cell clone and eliminate toxic free light chain production. Only in a minority of patients the plasma cell clone is completely eradicated; residual light chain production may still exist while clonal relapse may occur. We used sensitive next-generation flow cytometry (NGF) to detect minimal residual disease (MRD) in AL amyloidosis patients at complete haematologic response.

Bortezomib, Melphalan, and Dexamethasone for Light-Chain Amyloidosis.

Purpose: Oral melphalan and dexamethasone (MDex) were considered a standard of care in light-chain (AL) amyloidosis. In the past decade, bortezomib has been increasingly used in combination with alkylating agents and dexamethasone. We prospectively compared the efficacy and safety of MDex and MDex with the addition of bortezomib (BMDex).

Monitoring Plasma Cell Dyscrasias With Cell-free DNA Analysis.

The analysis of cell-free tumor DNA (cfDNA) has emerged as a promising method to determine the evolving genomic landscape of the whole tumor compartment, mainly in solid malignancies. Plasma cell dyscrasias are characterized by complex and constantly changing genomic aberrations that are important in terms of prognosis, evaluation of the minimal residual disease, and response monitoring. In multiple myeloma, the detection of clonal immunoglobulin rearrangements and driver gene mutations in the cfDNA has shown high concordance rates with their identification in bone marrow-derived tumor DNA.

Organ-specific manifestations of COVID-19 infection.

Although COVID-19 presents primarily as a lower respiratory tract infection transmitted via air droplets, increasing data suggest multiorgan involvement in patients that are infected. This systemic involvement is postulated to be mainly related to the SARS-CoV-2 virus binding on angiotensin-converting enzyme 2 (ACE2) receptors located on several different human cells. Lung involvement is the most common serious manifestation of the disease, ranging from asymptomatic disease or mild pneumonia, to severe disease associated with hypoxia, critical disease associated with shock, respiratory failure and multiorgan failure or death.

Timing and impact of a deep response in the outcome of patients with systemic light chain (AL) amyloidosis.

A rapid and deep haematologic response is fundamental in order to improve outcomes of patients with AL amyloidosis. We evaluated the impact of timing and depth of haematologic response at early time points (at 1 and 3 months from the start of therapy) in 227 consecutive previously untreated AL patients, who received bortezomib-based primary therapy. After 1 month of therapy, 30.

Ex Vivo Models Simulating the Bone Marrow Environment and Predicting Response to Therapy in Multiple Myeloma.

Multiple myeloma (MM) remains incurable despite the abundance of novel drugs. As it has been previously shown, preclinical 2D models fail to predict disease progression due to their inability to simulate the microenvironment of the bone marrow. In this review, we focus on 3D models and present all currently available ex vivo MM models that fulfil certain criteria, such as development of complex 3D environments using patients' cells and ability to test different drugs in order to assess personalized MM treatment efficacy of various regimens and combinations.

Investigating the Vascular Toxicity Outcomes of the Irreversible Proteasome Inhibitor Carfilzomib.

Background: Carfilzomib's (Cfz) adverse events in myeloma patients include cardiovascular toxicity. Since carfilzomib's vascular effects are elusive, we investigated the vascular outcomes of carfilzomib and metformin (Met) coadministration.

Methods: Mice received: (i) saline; (ii) Cfz; (iii) Met; (iv) Cfz+Met for two consecutive (acute) or six alternate days (subacute protocol).

Systemic autoimmune diseases, anti-rheumatic therapies, COVID-19 infection risk and patient outcomes.

As of June 10th 2020 about 7.2 million individuals have tested positive for, and more than 410,000 have died due to COVID-19. In this review we outline the pathophysiology that underpins the potential use of anti-rheumatic therapies for severe COVID-19 infection and summarize the current evidence regarding the risk and outcome of COVID-19 in patients with systemic autoimmune diseases.

The Emerging Role of Convalescent Plasma in the Treatment of COVID-19.

Various agents are currently under evaluation as potential treatments in the fight against coronavirus disease 2019 (COVID-19). Plasma from patients that have overcome COVID-19 infection, referred to as convalescent plasma, is a treatment option with considerable background in viral diseases such as Spanish influenza, H1N1, Ebola, Severe Acute Respiratory Syndrome (SARS), and Middle East Respiratory Syndrome (MERS). Although convalescent plasma has historically proven beneficial in the treatment of some viral diseases, its use is still explorative in the context of COVID-19.

Multiple myeloma: Current and future management in the aging population.

The increasing lifespan of the world population and the novel therapeutic combinations for the treatment of multiple myeloma (MM), which are more efficacious and safer, make the question of how to manage the older patient with MM increasingly relevant. Clinical trial data come mostly from subgroup analysis, as no clinical trials have been designed for elderly patients with MM, particularly the octogenarian population. Age has been traditionally used as a surrogate marker of physiological decline but does not accurately reflect frailty on its own.

The current role of BTK inhibitors in the treatment of Waldenstrom's Macroglobulinemia.

Introduction: Waldenstrom's Macroglobulinemia (WM) is a rare, indolent lymphoplasmacytic lymphoma characterized by heterogeneous clinical and genomic profile. Bruton's tyrosine kinase (BTK) is central to the signaling pathways required for clonal WM cell survival, and BTK inhibitors currently have an imperative role in the treatment of WM.

Areas Covered: The central role of BTK in WM will be described, and the rationale behind the development of BTKi.

Adverse event management in the TOURMALINE-MM3 study of post-transplant ixazomib maintenance in multiple myeloma.

The phase 3, double-blind, placebo-controlled TOURMALINE-MM3 study (NCT02181413) demonstrated improved progression-free survival with ixazomib maintenance versus placebo post autologous stem cell transplant (ASCT) in multiple myeloma patients. We report additional safety data from TOURMALINE-MM3 to inform adverse event (AE) management recommendations. Patients were randomized 3:2 to receive ixazomib (n = 395) or placebo (n = 261) on days 1, 8, and 15 of 28-day cycles for ~ 2 years or until progressive disease/toxicity.

Early M-Protein Dynamics Predicts Progression-Free Survival in Patients With Relapsed/Refractory Multiple Myeloma.

This study aimed to predict long-term progression-free survival (PFS) using early M-protein dynamic measurements in patients with relapsed/refractory multiple myeloma (MM). The PFS was modeled based on dynamic M-protein data from two phase III studies, POLLUX and CASTOR, which included 569 and 498 patients with relapsed/refractory MM, respectively. Both studies compared active controls (lenalidomide and dexamethasone, and bortezomib and dexamethasone, respectively) alone vs.