Herein, we present the final report of a single-center, prospective phase II study evaluating ibrutinib 420 mg once daily in 30 treatment-naive patients with Waldenstrom macroglobulinemia (WM). The present study is registered with ClinicalTrials.Gov (NCT02604511). With a median follow-up of 50 months, the overall, major, and VGPR response rates were 100%, 87%, and 30%. The VGPR rate was numerically but not significantly lower in patients with than without CXCR4 mutations (14% vs. 44%; p = 0.09). The median time to a minor response was 0.9 months, and to a major response was 1.9 months, though were longer in those with mutated CXCR4 at 1.7 months (p = 0.07) and 7.3 months (p = 0.01). Six patients had disease progression. The median progression-free survival (PFS) was not reached, and the 4-year PFS rate was 76%. There was also a non-significant lower 4-year PFS rate in patients with than without CXCR4 mutations (59% vs. 92%; p = 0.06). The most common treatment-related adverse events were fatigue, upper respiratory infection, and hematoma. Atrial fibrillation occurred in 20% of patients. Ibrutinib monotherapy induced durable responses in treatment-naive patients with WM. CXCR4 mutations impacted VGPR attainment, time to major response, and 4-year PFS rate.

PURPOSE BCL2 is overexpressed and confers prosurvival signaling in malignant lymphoplasmacytic cells in Waldenström macroglobulinemia (WM). Venetoclax is a potent BCL2 antagonist and triggers in vitro apoptosis of WM cells. The activity of venetoclax in WM remains to be clarified. PATIENTS AND METHODS We performed a multicenter, prospective phase II study of venetoclax in patients with previously treated WM ( NCT02677324 ). Venetoclax was dose-escalated from 200 mg to a maximum dose of 800 mg daily for up to 2 years. RESULTS Thirty-two patients were evaluable, including 16 previously exposed to Bruton tyrosine kinase inhibitors (BTKis). All patients were MYD88 L265P–mutated, and 17 carried CXCR4 mutations. The median time to minor and major responses was 1.9 and 5.1 months, respectively. Previous exposure to BTKis was associated with a longer time to response (4.5 v 1.4 months; P < .001). The overall, major, and very good partial response rates were 84%, 81%, and 19%, respectively. The major response rate was lower in those with refractory versus relapsed disease (50% v 95%; P = .007). The median follow-up time was 33 months, and the median progression-free survival was 30 months. CXCR4 mutations did not affect treatment response or progression-free survival. The only recurring grade ≥ 3 treatment-related adverse event was neutropenia (n = 14; 45%), including one episode of febrile neutropenia. Laboratory tumor lysis without clinical sequelae occurred in one patient. No deaths have occurred. CONCLUSION Venetoclax is safe and highly active in patients with previously treated WM, including those who previously received BTKis. CXCR4 mutation status did not affect treatment response.

This study investigates relationships between older prisoners' social experiences and their levels of distress. One hundred and seventy-three older prisoners (aged ≥ 50 years) from 8 Australian prisons were administered the Kessler Psychological Distress (K10) Scale, with additional information collected via individual interviews. Psychological distress scores were significantly associated with measures of self-reported safety (p < .001), prison victimization (p < .05), perceived social support from staff (p < .01) and inmates (p < .001), current employment (p < .05), and level of exercise (p < .001) among older inmates. Findings suggest that strategies for improving sense of safety, social support and level of exercise may ameliorate distress among older prisoners.

This exploratory study sought to investigate how a small sample of self-selected women attending hospital for a miscarriage in the first 20 weeks of pregnancy experienced the treatment they received. Six women who had a miscarriage between June 2006 and December 2007, and sought treatment at six Melbourne metropolitan hospitals, participated in semi-structured interviews during August-September 2008. Thematic analysis revealed that participants perceived hospital responses to miscarriage to be inadequate. Findings suggested that there was no consistent response, there was little compassion or acknowledgement of the miscarriage and that information provision was largely absent; social workers were rarely involved. Participants indicated that they wanted a more consistent and specialized hospital response, with timely access to diagnostic testing equipment as necessary, the offer of social work, information provision and staff to be compassionate in their care and to acknowledge their pregnancy loss.

The prison population in most jurisdictions is escalating. As many prisoners are also parents, more children will inevitably be affected by the experience of having a parent incarcerated. Police and the lower courts are the gatekeepers of the criminal justice system and make urgent and vital decisions about arrest, remand and sentencing which have critical consequences for the children of those arrested, remanded and sentenced. To better understand how these children are responded to by this adult system, this paper draws on data collected from a purposive sample (N ¼ 16) of Victorian magistrates, legal representatives and police, as part of a broader ARC funded study. Findings indicate that the consideration of these children by police and magistrates is largely ad hoc and depends on good will and the exercise of discretion. The balancing of justice issues and the interests of children is also complex and currently under-researched and under-informed. The authors argue that until the agencies dealing with adults incorporate child-focused practices, children, who have a primary carer in prison, will continue to be disadvantaged by a system which considers them only as collateral damage in the exercise of justice.