Uptake of novel therapies into first-line treatment for acute myeloid leukemia patients: EU4 + UK perspective.

To explore the incorporation of novel agents in the first-line setting for acute myeloid leukemia patients. Observational study based on data from a multi-country cross-sectional retrospective web-based survey sent to 518 physicians in Europe between 2020 and 2021. Information from 2040 patients was analyzed.

A phase 2 clinical trial of combined BRAF/MEK inhibition for BRAFV600E-mutated multiple myeloma.

Activating BRAF mutations are found in a small subset of patients with newly diagnosed multiple myeloma, but prevalence increases in late-stage, refractory disease, and the mutations are associated with adverse outcome. This prospective single-arm, open-label, multicenter phase 2 trial assessed the efficacy and safety of combined BRAF/MEK inhibition, using encorafenib and binimetinib, in patients with relapsed/refractory multiple myeloma (RRMM) carrying a BRAFV600E mutation. Patients received 450 mg encorafenib once daily and binimetinib 45 mg twice daily.

First-line therapy with bendamustine/prednisone/bortezomib-A GMMG trial for non-transplant eligible symptomatic multiple myeloma patients.

Objectives: The German-speaking Myeloma Multicenter Group (GMMG) conducted this trial to investigate efficacy and safety of the three-drug combination bendamustine/prednisone/bortezomib (BPV) as first-line therapy for elderly patients with multiple myeloma (MM).

Methods: Elderly MM patients requiring first-line therapy and not eligible for intensive treatment were enrolled in this phase IIb multicenter study. Patients were treated with BPV regimen for a maximum of nine cycles.

Effects of central and peripheral cueing on perceptual and saccade performance.

Previous research on the spatiotemporal dynamics of exogenous and endogenous attentional allocation during saccade preparation yielded conflicting results. We hypothesize that this can be explained by the cueing type used to orient attention in a perceptual task. We investigated the time-course of attentional allocation as a function of cueing type (central vs peripheral), spatial congruency of the cued perceptual and saccade task locations, and cue validity in a dual-task paradigm.

Inhibition in movement plan competition: reach trajectories curve away from remembered and task-irrelevant present but not from task-irrelevant past visual stimuli.

The current study investigated the role of automatic encoding and maintenance of remembered, past, and present visual distractors for reach movement planning. The previous research on eye movements showed that saccades curve away from locations actively kept in working memory and also from task-irrelevant perceptually present visual distractors, but not from task-irrelevant past distractors. Curvature away has been associated with an inhibitory mechanism resolving the competition between multiple active movement plans.

Diagnostic and therapeutic approaches to multiple myeloma patients: 'Real-world' data from representative multicentre treatment surveys in Germany between 2008 and 2011.

A survey was conducted to investigate the standard of care for multiple myeloma in Germany, in order to clarify the status of implementation of international and national treatment guidelines. In addition, the changes in disease management over time were investigated by comparison with surveys conducted in 2008 and 2009. The survey captured a representative sample of 478 myeloma patients with a mean age of 67.

Increased microcirculation detected by dynamic contrast-enhanced magnetic resonance imaging is of prognostic significance in asymptomatic myeloma.

This prospective study aimed to investigate the prognostic significance of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) as a non-invasive imaging technique delivering the quantitative parameters amplitude A (reflecting blood volume) and exchange rate constant kep (reflecting vascular permeability) in patients with asymptomatic monoclonal plasma cell diseases. We analysed DCE-MRI parameters in 33 healthy controls and 148 patients with monoclonal gammopathy of undetermined significance (MGUS) or smouldering multiple myeloma (SMM) according to the 2003 IMWG guidelines. All individuals underwent standardized DCE-MRI of the lumbar spine.

A Furan-Based Lewis-Y-(CD174)-Saccharide Mimetic Inhibits Endothelial Functions and In Vitro Angiogenesis.

Background: Angiogenesis is a fundamental process underlying cancer progression and autoimmune disease. Lewis Y is known as a regulated glycan-structure supporting human endothelial function and angiogenesis.

Objectives: We hypothesize that Lewis Y based analogues interfere with Lewis Y mediated endothelial functions and angiogenesis.

The influence of spatial congruency and movement preparation time on saccade curvature in simultaneous and sequential dual-tasks.

Saccade curvature represents a sensitive measure of oculomotor inhibition with saccades curving away from covertly attended locations. Here we investigated whether and how saccade curvature depends on movement preparation time when a perceptual task is performed during or before saccade preparation. Participants performed a dual-task including a visual discrimination task at a cued location and a saccade task to the same location (congruent) or to a different location (incongruent).

Prognostic significance of increased bone marrow microcirculation in newly diagnosed multiple myeloma: results of a prospective DCE-MRI study.

Objectives: Aim of this prospective study was to investigate prognostic significance of increased bone marrow microcirculation as detected by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for survival and local complications in patients with multiple myeloma (MM).

Methods: We performed DCE-MRI of the lumbar spine in 131 patients with newly diagnosed MM and analysed data according to the Brix model to acquire amplitude A and exchange rate constant kep. In 61 patients a second MRI performed after therapy was evaluated to assess changes in vertebral height and identify vertebral fractures.

Effects of spatial congruency on saccade and visual discrimination performance in a dual-task paradigm.

The present study investigated the coupling of selection-for-perception and selection-for-action during saccadic eye movement planning in three dual-task experiments. We focused on the effects of spatial congruency of saccade target (ST) location and discrimination target (DT) location and the time between ST-cue and Go-signal (SOA) on saccadic eye movement performance. In two experiments, participants performed a visual discrimination task at a cued location while programming a saccadic eye movement to a cued location.

The application of Gadopentate-Dimeneglumin has no impact on progression free and overall survival as well as renal function in patients with monoclonal plasma cell disorders if general precautions are taken.

Objectives: The current analysis investigated the prognostic significance of gadopentetate dimeglumine on survival and renal function in patients with monoclonal plasma cell disorders.

Methods: In this study 263 patients who had received gadopentetate dimeglumine within a prospective trial investigating dynamic contrast-enhanced magnetic resonance imaging (MRI) were compared with 335 patients who had undergone routine, unenhanced MRI.

Results: We found no significant prognostic impact of the application of contrast agent on progression-free survival in patients with either monoclonal gammopathy of undetermined significance, smouldering or symptomatic myeloma and no significant prognostic impact on overall survival in patients with symptomatic myeloma.

Dynamic contrast-enhanced magnetic resonance imaging for assessment of antiangiogenic treatment effects in multiple myeloma.

Purpose: To noninvasively assess bone marrow microcirculation before and after therapy in patients with newly diagnosed multiple myeloma with dynamic contrast-enhanced MRI (DCE-MRI).

Experimental Design: Ninety-six patients received DCE-MRI before and after primary treatment for newly diagnosed multiple myeloma. For the 91 evaluable patients, treatment consisted of high-dose therapy (HDT) with autologous stem cell transplantation (ASCT) in 82 patients and chemotherapy without ASCT in 9 patients.

The glycome of normal and malignant plasma cells.

The glycome, i.e. the cellular repertoire of glycan structures, contributes to important functions such as adhesion and intercellular communication.

Treatment with Thalidomide and Cyclophosphamide (TCID) is Superior to Vincristine (VID) and to Vinorelbine (VRID) Regimens in Patients with Refractory or Recurrent Multiple Myeloma.

Treatment of relapsed or refractory multiple myeloma remains a challenge and novel treatment regimen are required. Here, a matched pair analysis was performed comparing TCID (thalidomide, cyclophosphamide, idarubicin, dexamethasone) treatment to the treatment of patients with VID (vincristine, idarubicin, dexamethasone) or with VRID (vinorelbine, idarubicin, dexamethasone) for relapsed or refractory multiple myeloma. In total, 197 patients were enrolled in multicenter trials.

Bisphosphonate treatment and renal function in 201 myeloma patients undergoing stem cell transplantation.

Administration of bisphosphonates (BPs) is an essential supportive treatment for reducing bone-related complications in cancer. Deterioration of renal function is one possible side effect of BPs as well as a clinical feature in multiple myeloma. It has been suggested that the nephrotoxicity of different BPs may differ.

Sorafenib in patients with refractory or recurrent multiple myeloma.

Sorafenib is a small molecular inhibitor of several tyrosine protein kinases, including vascular endothelial growth factor receptor, platelet-derived growth factor receptor and rapidly accelerated fibrosarcoma kinases, targeting signal transduction and angiogenic pathways. It is approved for the treatment of advanced renal cell carcinoma and hepatocellular carcinoma. The objectives of this prospective phase II trial were to assess the activity and tolerability of sorafenib in patients with recurrent or refractory myeloma.

Clinical experience with thalidomide and lenalidomide in multiple myeloma.

Thal has antiangiogenic and immunomodulatory activity. Clinical research provided clear evidence that Thal belongs to the most active drugs for the treatment of multiple myeloma e.g.

Thalidomide versus dexamethasone for the treatment of relapsed and/or refractory multiple myeloma: results from OPTIMUM, a randomized trial.

Background: Thalidomide has potent antimyeloma activity, but no prospective, randomized controlled trial has evaluated thalidomide monotherapy in patients with relapsed/refractory multiple myeloma.

Design And Methods: We conducted an international, randomized, open-label, four-arm, phase III trial to compare three different doses of thalidomide (100, 200, or 400 mg/day) with standard dexamethasone in patients who had received one to three prior therapies. The primary end-point was time to progression.

Therapy of relapsed and refractory multiple myeloma.

Despite considerable improvements in first line treatment still the majority of patients experience relapse of multiple myeloma. Treatment decisions for relapse or refractory multiple myeloma should be based on a clinical decision path taking response and adverse events to previous therapy, myeloma specific complications and organ dysfunctions, overall clinical condition, age, cytogenetic information and prognostic factors into account. Bortezomib, thalidomide and lenalidomide have improved the therapeutic armentarium for patients with refractory or relapsed disease and are often used in combination with dexamethasone or chemotherapeutic agents.

Monoclonal gammopathy and smoldering multiple myeloma: diagnosis, staging, prognosis, management.

Monoclonal gammopathy of unknown significance (MGUS) as one of the most common premalignant disorders and smoldering multiple myeloma (sMM) are both caused by a proliferation of monoclonal plasma cells leading to a detectable serum monoclonal protein and/or excess of plasma cells in the bone marrow. Prerequisite for the diagnosis is that plasma cell disease does not cause clinical symptoms. Cytogenetic aberrations are detectable in the majority of patient in the clonally expanded plasma cells.

Molecular pathogenesis of multiple myeloma: chromosomal aberrations, changes in gene expression, cytokine networks, and the bone marrow microenvironment.

This chapter focuses on two aspects of myeloma pathogenesis: (1) chromosomal aberrations and resulting changes in gene and protein expression with a special focus on growth and survival factors of malignant (and normal) plasma cells and (2) the remodeling of the bone marrow microenvironment induced by accumulating myeloma cells. We begin this chapter with a discussion of normal plasma cell generation, their survival, and a novel class of inhibitory factors. This is crucial for the understanding of multiple myeloma, as several abilities attributed to malignant plasma cells are already present in their normal counterpart, especially the production of survival factors and interaction with the bone marrow microenvironment (niche).

Combined phase I/II study of imexon (AOP99.0001) for treatment of relapsed or refractory multiple myeloma.

Imexon [AOP99.0001 (4-imino-1,3-diazobicyclo[3. 1.

Prognostic significance of focal lesions in whole-body magnetic resonance imaging in patients with asymptomatic multiple myeloma.

Purpose: With whole-body magnetic resonance imaging (wb-MRI), almost the whole bone marrow compartment can be examined in patients with monoclonal plasma cell disease. Focal lesions (FLs) detected by spinal MRI have been of prognostic significance in symptomatic multiple myeloma (sMM). In this study, we investigated the prognostic significance of FLs in wb-MRI in patients with asymptomatic multiple myeloma (aMM).

Transcriptional regulation of the vascular endothelial glycome by angiogenic and inflammatory signalling.

Vascular endothelial cells undergo many molecular changes during pathological processes such as inflammation and tumour development. Tumours such as malignant lymphomas affecting bone marrow are dependent on interactions with endothelial cells for (1) site-specific homing and (2) tumour-induced angiogenesis. Modifications in glycosylation are responsible for fine-tuning of distinct endothelial surface receptors.