Background Maintenance therapy following autologous stem cell transplantation can delay disease progression and prolong survival in multiple myeloma (MM). Ixazomib is ideally suited for maintenance therapy given its efficacy, convenient once-weekly oral dosing, and low toxicity profile. Methods The phase 3, double-blind, placebo-controlled, TOURMALINE-MM3 study randomised 656 patients with newly diagnosed MM from 227 clinical/hospital sites in 30 countries in Europe, the Middle East, Africa,

Background Emerging data from longitudinal studies suggests that low sex steroid concentrations in men are associated with increased cardiovascular risk and mortality. The impact of longitudinal trajectory patterns from serial sex steroid and gonadotropin measurements on the observed associations is unknown to date. Methods We prospectively evaluated 254 elderly men (mean age: 75.5 years) of the Framingham Heart Study with up to four serial measurements of serum total testosterone (TT), dehydroepiandrosterone sulfate (DHEAS), follicle stimulating hormone (FSH), luteinizing hormone (LH), and total estradiol (EST); and constructed age- and multivariable-adjusted Cox proportional hazard regression models relating baseline hormone concentrations and their mean, slope, and variation over time (modelled as continuous and categorized into quartiles) to the incidence of clinical cardiovascular disease (CVD) and all-cause mortality at 5-years and 10-years of follow-up. Results We observed no association between baseline concentrations of sex steroids, gonadotropins, and their trajectories with incident clinical CVD over 5-years and 10-years follow-up, respectively. Although higher baseline TT concentrations were associated with lower mortality risk at 5-years (hazard ratio per quartile increment, 0.74; 95% confidence interval, 0.56 – 0.98), correction for multiple statistical testing (p <0.005) rendered this association statistically non-significant. Repeat analyses at the 10-year follow-up time point also demonstrated no significant association between sex steroids, gonadotropins, or their trajectories and mortality. Conclusion Investigating longitudinal trajectory patterns of serial sex steroid and gonadotropin measurements, the present study found no consistent associations with incident clinical CVD and all-cause mortality risk in elderly men in the community.

No abstract

The failure rate for phase III trials in oncology is high; quantitative predictive approaches are needed. We developed a model‐based meta‐analysis (MBMA) framework to predict progression‐free survival (PFS) from overall response rates (ORR) in relapsed/refractory multiple myeloma (RRMM), using data from seven phase III trials. A Bayesian analysis was used to predict the probability of technical success (PTS) for achieving desired phase III PFS targets based on phase II ORR data. The model demonstrated a strongly correlated (R2 = 0.84) linear relationship between ORR and median PFS. As a representative application of the framework, MBMA predicted that an ORR of ∼66% would be needed in a phase II study of 50 patients to achieve a target median PFS of 13.5 months in a phase III study. This model can be used to help estimate PTS to achieve gold‐standard targets in a target product profile, thereby enabling objectively informed decision‐making.