Targeting Bruton tyrosine kinase with ibrutinib in relapsed/refractory marginal zone lymphoma.

Marginal zone lymphoma (MZL) is a heterogeneous B-cell malignancy for which no standard treatment exists. MZL is frequently linked to chronic infection, which may induce B-cell receptor (BCR) signaling, resulting in aberrant B-cell survival and proliferation. We conducted a multicenter, open-label, phase 2 study to evaluate the efficacy and safety of ibrutinib in previously treated MZL. Patients with histologically confirmed MZL of all subtypes who received ≥1 prior therapy with an anti-CD20 antibody-containing regimen were treated with 560 mg ibrutinib orally once daily until progression or unacceptable toxicity. The primary end point was independent review committee-assessed overall response rate (ORR) by 2007 International Working Group criteria. Among 63 enrolled patients, median age was 66 years (range, 30-92). Median number of prior systemic therapies was 2 (range, 1-9), and 63% received ≥1 prior chemoimmunotherapy. In 60 evaluable patients, ORR was 48% (95% confidence interval [CI], 35-62). With median follow-up of 19.4 months, median duration of response was not reached (95% CI, 16.7 to not estimable), and median progression-free survival was 14.2 months (95% CI, 8.3 to not estimable). Grade ≥3 adverse events (AEs; >5%) included anemia, pneumonia, and fatigue. Serious AEs of any grade occurred in 44%, with grade 3-4 pneumonia being the most common (8%). Rates of discontinuation and dose reductions due to AEs were 17% and 10%, respectively. Single-agent ibrutinib induced durable responses with a favorable benefit-risk profile in patients with previously treated MZL, confirming the role of BCR signaling in this malignancy. As the only approved therapy, ibrutinib provides a treatment option without chemotherapy for MZL. This study is registered at www.clinicaltrials.gov as #NCT01980628.

Neighborhood predictors of hopelessness among adolescent suicide attempters: preliminary investigation.

The role of neighborhood factors in predicting hopelessness among adolescent suicide attempters was examined in this study. Forty-eight adolescents who attempted suicide were administered measures of hopelessness and depression. Family socioeconomic status (SES) was calculated based on family demographics and characteristics of neighborhood context were examined using a geocoding software package. Adolescents who lived in neighborhoods with weak social networks reported higher levels of hopelessness, even after controlling for SES and depression. These preliminary findings suggest that environmental context may play a role in the emotional status of adolescents who attempt suicide.

Associations between youth risk behavior and exposure to violence: implications for the provision of mental health services in urban schools.

This article assesses the relation between health risk behaviors and varying levels of exposure to violence in an effort to inform assessment and intervention efforts of a school-based mental health program serving inner-city youth. Health risk behaviors such as involvement in violence, risky sexual behavior, and substance use are clearly associated, both with each other and with violence exposure. However, differential relationships were observed depending on the nature of violence exposure. Knowledge of violence was associated with substance use and sexual behavior variables. Witnessing violence was associated with violence involvement, substance use, and exercise variables. Finally, violent victimization was associated with violence involvement and sexual behavior variables. A more complete understanding of the associations among health risk factors and violence exposure variables has the potential to improve implementation of school mental health services for urban youth.