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

The Role of Auditory Features Within Slot-Themed Social Casino Games and Online Slot Machine Games

Over the last few years playing social casino games has become a popular entertainment activity. Social casino games are offered via social media platforms and mobile apps and resemble gambling activities. However, social casino games are not classified as gambling as they can be played for free, outcomes may not be determined by chance, and players receive no monetary payouts. Social casino games appear to be somewhat similar to online gambling activities in terms of their visual and auditory features, but to date little research has investigated the cross over between these games. This study examines the auditory features of slot-themed social casino games and online slot machine games using a case study design. An example of each game type was played on three separate occasions during which, the auditory features (i.e., music, speech, sound effects, and the absence of sound) within the games were logged. The online slot-themed game was played in demo mode. This is the first study to provide a qualitative account of the role of auditory features within a slot-themed social casino game and an online slot machine game. Our results found many similarities between how sound is utilised within the two games. Therefore the sounds within these games may serve functions including: setting the scene for gaming, creating an image, demarcating space, interacting with visual features, prompting players to act, communicating achievements to players, providing reinforcement, heightening player emotions and the gaming experience. As a result this may reduce the ability of players to make a clear distinction between these two activities, which may facilitate migration between game

Recent Improvements in the SLC Positron System Performance

The positron system is very specific to the SLC in that the positrons are accelerated in the same linac as the electrons that produce them and the electrons with which they collide. Some of the difficulties in tuning this system to peak performance are thus unlikely to be encountered in future linear colliders, but many of the lessons learned in beam matching are useful for future machines. The design and commissioning of this system has been previously reported so we only briefly describe the major subsystems before detailing the tuning and diagnostics involved in optimizing the performance of the overall system

Recent Improvements in the SLC Positron System Performance

The positron system is very specific to the SLC in that the positrons are accelerated in the same linac as the electrons that produce them and the electrons with which they collide. Some of the difficulties in tuning this system to peak performance are thus unlikely to be encountered in future linear colliders, but many of the lessons learned in beam matching are useful for future machines. The design and commissioning of this system has been previously reported so we only briefly describe the major subsystems before detailing the tuning and diagnostics involved in optimizing the performance of the overall system

Coherent-Radiation Spectroscopy of Few-Femtosecond Electron Bunches Using a Middle-Infrared Prism Spectrometer

Modern, high-brightness electron beams such as those from plasma wakefield accelerators and free-electron laser linacs continue the drive to ever-shorter bunch durations. In low-charge operation (∼20  pC), bunches shorter than 10 fs are reported at the Linac Coherent Light Source (LCLS). Though suffering from a loss of phase information, spectral diagnostics remain appealing as compact, low-cost bunch duration monitors suitable for deployment in beam dynamics studies and operations instrumentation. Progress in middle-infrared (MIR) imaging has led to the development of a single-shot, MIR prism spectrometer to characterize the corresponding LCLS coherent beam radiation power spectrum for few-femtosecond scale bunch length monitoring. In this Letter, we report on the spectrometer installation as well as the temporal reconstruction of 3 to 60 fs-long LCLS electron bunch profiles using single-shot coherent transition radiation spectra

PEP-II Status and Outlook

PEP-II/BABAR are presently in their second physics run. With machine and detector performance and reliability at an all-time high, almost 51 fb{sup -1} have been integrated by BABAR up to mid-October 2001. PEP-II luminosity has reached 4.4 x 10{sup 33} cm{sup -2} s{sup -1} and our highest monthly delivered luminosity has been above 6 pb{sup -1}, exceeding the performance parameters given in the PEP-II CDR by almost 50%. The increase compared to the first run in 2000 has been achieved by a combination of beam-current increase and beam-size decrease. In this paper we will summarize the PEP-II performance and the present limitations as well as our plans to further increase machine performance