Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma

Daratumumab, a human CD38 immunoglobulin G1 kappa (IgG1κ) monoclonal antibody, has activity as monotherapy in multiple myeloma (MM). This phase 1/2 study investigated daratumumab plus lenalidomide/dexamethasone in refractory and relapsed/refractory MM. Part 1 (dose escalation) evaluated 4 daratumumab doses plus lenalidomide (25 mg/day orally on days 1-21 of each cycle) and dexamethasone (40 mg/week). Part 2 (dose expansion) evaluated daratumumab at the recommended phase 2 dose (RP2D) plus lenalidomide/dexamethasone. Safety, efficacy, pharmacokinetics, immunogenicity, and accelerated daratumumab infusions were studied. In part 1 (13 patients), no dose-limiting toxicities were observed, and 16 mg/kg was selected as the R2PD. In part 2 (32 patients), median time since diagnosis was 3.2 years, with a median of 2 prior therapies (range, 1-3 prior therapies), including proteasome inhibitors (91%), alkylating agents (91%), autologous stem cell transplantation (78%), thalidomide (44%), and lenalidomide (34%); 22% of patients were refractory to the last line of therapy. Grade 3 to 4 adverse events (≥5%) included neutropenia, thrombocytopenia, and anemia. In part 2, infusion-related reactions (IRRs) occurred in 18 patients (56%); most were grade ≤2 (grade 3, 6.3%). IRRs predominantly occurred during first infusions and were more common during accelerated infusions. In part 2 (median follow-up of 15.6 months), overall response rate was 81%, with 8 stringent complete responses (25%), 3 complete responses (9%), and 9 very good partial responses (28%). Eighteen-month progression-free and overall survival rates were 72% (95% confidence interval, 51.7-85.0) and 90% (95% confidence interval, 73.1-96.8), respectively. Daratumumab plus lenalidomide/dexamethasone resulted in rapid, deep, durable responses. The combination was well tolerated and consistent with the safety profiles observed with lenalidomide/dexamethasone or daratumumab monotherapy. This trial was registered at www.clinicaltrials.gov as #NCT01615029

Strategisches Handeln von Startups im Kontext der Mediatisierung

Junge Gründer und Start-ups müssen sich in einer schnell wandelnden und mediatisierten Wettbewerbsumwelt behaupten. Ihr Handeln wird geprägt von sozialen Netzwerkmedien wie Facebook, LinkedIn oder Instagram. Um auf diesen Medien-plattformen erfolgreich zu sein, müssen Markenführung und Markenkommunikation strategisch verankert sein. Der Aufsatz präsentiert daher eine qualitative Analyse empirischer Daten aus dem Kontext des Start-up-Incubator neudeli der Bauhaus-Universität Weimar und verdeutlicht, dass die Mediatisierung grundlegend in die strategische Entwicklung der Marke von jungen Gründern und Start-ups eingreift. Die Studie verdeutlicht das Verständnis strategischer Markenführung in mediatisierten Kontexten und zeigt, dass drei idealtypische Praktiken zur Markenführung und strategischen Entwicklung beitragen: 1) Bürokratische Medienarbeit, 2) Mediale Kreativarbeit, 3) Netzwerkarbeit durch Medien

Optimal shape of a cold-neutron triple-axis spectrometer

We have performed a McStas optimization of the primary spectrometer for a generic 40 m long, cold-neutron triple-axis spectrometer with a doubly focusing monochromator. The optimal design contains an elliptically focusing guide, a virtual source point before a low-grade PG monochromator, and non-equidistant focusing at the monochromator. The flux at 5 meV shows a gain factor 12 over the "classical" design with a straight 12 x 3 cm(2), m=2 guide and a vertically focusing PG monochromator. In addition, the energy resolution was found to be improved. This unexpectedly large design improvement agrees with the Liouville theorem and can be understood as the product of many smaller gain factors, combined with a more optimal utilization of the beam divergence within the guide. Our results may be relevant for a possible upgrade of a number of cold-neutron triple-axis spectrometers and for a possible triple-axis spectrometer at the European Spallation Source. (C) 2010 Elsevier B.V. All rights reserved