BACKGROUND: Advanced multiple myeloma (MM) and Waldenströ m's macroglobulinemia (WM) are incurable B-cell malignancies. This is the first full clinical report of atacicept, a fusion protein that binds to and neutralises the B-cell survival factors, B-lymphocyte stimulator (BLyS) and A proliferation-inducing ligand (APRIL), in MM and WM. METHODS: In this open-label phase-I study, 16 patients with advanced disease (12 MM, 4 WM) received one cycle of five once-weekly subcutaneous injections of atacicept (2, 4, 7 or 10 mg kg À1 ). Patients with stable disease after cycle 1 entered an extension study (either two additional cycles (2, 4 and 7 mg kg À1 cohorts) or 15 consecutive weekly injections of atacicept 10 mg kg À1 ).

Background The SENIORS trial showed that nebivolol reduced the risk of death or cardiovascular (CV)

In patients with heart failure and advanced systolic LV dysfunction, nebivolol reduces ventricular size and improves EF. The absence of detectable changes with standard echocardiography in patients with predominant diastolic heart failure questions the mechanism of benefit on morbidity/mortality in such patients.

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Objective To compare the durations of response achieved with adjunctive vagus nerve stimulation (VNS + TAU) vs treatment as usual (TAU) alone in treatment-resistant depression (TRD) over a 5-year period in the TRD registry. Materials and methods Data from 271 participants on TAU and 328 participants on VNS + TAU were analyzed. Response was defined as ≥50% decrease in baseline Montgomery–Åsberg Depression Rating Scale (MADRS) score at postbaseline visit and was considered retained until the decrease was <40%. MADRS was obtained quarterly in year 1 and biannually thereafter. Time-to-events were estimated using Kaplan–Meier method and compared using log-rank test. HR was estimated using Cox proportion hazard model. Results In the VNS + TAU arm, 62.5% (205/328) of participants had a first response over 5 years compared with 39.9% (108/271) in TAU. The time to first response was significantly shorter for VNS + TAU than for TAU ( P <0.01). For responders in the first year, median time to relapse from first response was 10.1 months (Q1=4.2, Q3=31.5) for VNS + TAU vs 7.3 months (Q1=3.1, Q3=17.6) for TAU ( P <0.01). HR=0.6 (95% CI: 0.4, 0.9) revealed a significantly lower chance for relapse in VNS + TAU. Probability of retaining first response for a year was 0.39 (0.27, 0.51) for TAU and 0.47 (0.38, 0.56) for VNS + TAU. Timing of the onset of the response did not impact the durability of the response. Conclusion VNS therapy added to TAU in severe TRD leads to rapid onset and higher likelihood of response, and a greater durability of the response as compared to TAU alone.