Safety and efficacy of zanubrutinib in relapsed/refractory marginal zone lymphoma: final analysis of the MAGNOLIA study.

The primary analysis of MAGNOLIA, an open-label, single-arm, multicenter, phase 2 study, demonstrated that the next-generation Bruton tyrosine kinase (BTK) inhibitor zanubrutinib provided a high overall response rate (ORR) in patients with relapsed/refractory marginal zone lymphoma (R/R MZL), with a favorable safety/tolerability profile. Presented here, is the final analysis of MAGNOLIA, performed to characterize the durability of response and longer-term safety and tolerability. Zanubrutinib (160 mg twice daily) was evaluated in 68 patients with R/R MZL who had received at least 1 anti-CD20-directed regimen. The primary end point was independent review committee (IRC)-assessed ORR. Secondary end points included investigator-assessed ORR, duration of response (DOR), progression-free survival (PFS), overall survival (OS), health-related quality of life, safety, and tolerability. With a median follow-up of 27.4 months, the IRC-assessed ORR was 68.2% (95% confidence interval [CI], 55.6-79.1), with a 24-month DOR event-free rate of 72.9% (95% CI, 54.4-84.9). PFS and OS at 24 months were 70.9% (95% CI, 57.2-81.0) and 85.9% (95% CI, 74.7-92.4), respectively. The zanubrutinib safety profile was consistent with the primary analysis, with no new safety signals observed. Atrial fibrillation/flutter (n = 2 [2.9%]) and hypertension (n = 3 [4.4%]) were uncommon. Neutropenia (n = 8 [11.8%]) was the most common grade ≥3 adverse event. In this final analysis of MAGNOLIA, zanubrutinib demonstrated sustained clinical responses beyond 2 years, with 73% of responders alive and progression free. Zanubrutinib continued to demonstrate a favorable safety/tolerability profile with the additional time on treatment. This trial was registered at www.clinicaltrials.gov as #NCT03846427.

Co-designed Mindful Parenting for Parents of Children with ADHD: A Pilot and Feasibility Study.

This mixed-methods single arm pilot study examined the feasibility, acceptability, and preliminary outcomes of a co-designed mindful parenting intervention for parents of children with ADHD, Parents that Mind (PTM). The 5-week parent-only intervention comprised two face-to-face group retreats and 5 weeks home practice. Eighteen parents of children with ADHD participated in PTM, completing self-report questionnaires and semi-structured interviews. Indicating high acceptability, 100% of parents interviewed reported PTM was helpful and they would recommend PTM. High feasibility of parents attending one face-to-face retreat was observed, with all parents attending the first retreat, however intervention adherence was challenging, with 55% of parents attending the second retreat. Barriers to intervention adherence included: lack of time, work commitments, illness and exhaustion. Quantitative data indicate promising preliminary effects for parents and children. Addressing the barriers raised by parents in this pilot appear necessary, before examining efficacy in a blinded RCT.

Electronic FRAIL score as a predictor of treatment outcomes in older patients with diffuse large B-cell lymphoma.

INTRODUCTION: Frailty is a significant risk factor for poor outcomes among older patients with diffuse large B-cell lymphoma (DLBCL). We present an automatically derived electronic frailty screening tool (FRAIL score) as a predictor of patient outcomes. METHODS: Patients aged 70 or over who received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy for DLBCL between 2010 and ` were retrospectively assessed for their FRAIL scores. Measured treatment outcomes included overall survival (OS), progression-free survival (PFS), and treatment-limiting toxicity from chemotherapy. RESULTS: A total of 96 patients were analysed. When stratified by FRAIL score, the estimated 5-year PFS was 58%, 48% and, 0% for those with scores of 0-1, 2, and 3-5, respectively (p = 0.012). Similarly, the estimated 5-year OS for these respective groups was 60%, 60% and 0% (p = 0.010). Patients with a FRAIL score of 3-5 were also more likely than those with a score of 0-1 to need dose reduction or treatment delay due to toxicity (odds ratio [OR] 12.5, 95% confidence interval [CI] 10.42-109.72) and less likely to complete the six planned cycles of treatment (OR 0.14, 95% CI 0.03-0.77). CONCLUSION: The FRAIL score is independently predictive of OS, PFS, and treatment-related toxicity in older patients with DLBCL receiving R-CHOP chemotherapy. Once implemented, it provides a quick and accessible method to stratify disease and treatment-related risk among these patients.

Paraprotein implicated in hardware failures in nucleic acid testing of blood donors.

BACKGROUND AND OBJECTIVES: Analyser blockage due to gel formation by paraproteins leading to invalid results is a rare problem in viral nucleic acid testing (NAT) at New Zealand Blood Service (NZBS) despite many blood samples tested without problems from individuals with known paraproteins. This study aimed to identify common factors in samples causing blockages. METHOD: Retrospective data were gathered on blood samples known to have blocked analysers at NZBS testing sites. Patients with plasma cell dyscrasia undergoing haematopoietic stem cell (HSC) harvest formed the comparator arm. These patients were identified from registry data of individuals undergoing autologous stem cell transplantation at Auckland City Hospital between 2013 and 2017. RESULTS: Four individuals were identified as having blocked analysers between 2010 and 2018. A total of 184 HSC transplant patients were identified, with contemporaneous paraprotein levels available for 177 (96%). Patients with intact immunoglobulin subtypes (134, 73%) were further analysed. Of these, 119 patients (65%) also had total protein and globulin levels available. Mean paraprotein (37.5 g/l), total protein (95.3 g/l), globulin levels (51.5 g/l) and proportion of lambda subtype (75%) were higher in the blocker group compared with non-blocking comparators (4.7 g/l, 66.8 g/l, 27.7 g/l, 36.6% respectively) (P = 0·03, 0·02, 0·007, 0·12). The highest paraprotein and total protein levels from the non-blocking cohort overlapped with the lowest of the blocker group. DISCUSSION: High protein levels (paraprotein >20 g/l, total protein >75 g/l) and a trend towards lambda subtype were associated with NAT analyser blockage. The overlap with non-blocking donor samples suggests factors in addition to protein quantity that are also important.

Experience of stress in parents of children with ADHD: A qualitative study.

Purpose: Qualitative research aimed at understanding the stress of parents of children with ADHD is limited and few interventions have been designed to directly target their stress. The study aim was to explore the stress of parents of children with ADHD using qualitative methodology.Methods: Thirteen parents of children with ADHD participated in two focus groups. Open-ended questions explored parents' experiences of stress. Focus groups were recorded, transcribed, and coded using thematic analysis. Parents also completed the Parenting Stress Index-Short Form.Results: Four primary themes were identified: The child's behaviour feels like a "wrecking ball"; Coping with the "war at home"; A divided family: "relationships don't survive"; and Craving support: "it's goddamn hard work". Five of eleven participants who completed the PSI-SF scored in the clinically significant range indicating levels of stress that require professional support.Conclusions: Parents attribute their high stress to their children's behaviour, unmet needs for support, and social stigma. Parents request support to enable them to cope and appear to represent a clinical population who require mental health care and support themselves. Future interventions directly targeting the stress of parents of children with ADHD may provide wide-ranging benefits for their children and families.

"Eat, pray, love. Ritalin": A qualitative investigation into the perceived barriers and enablers to parents of children with ADHD undertaking a mindful parenting intervention.

BACKGROUND AND PURPOSE: There is growing interest in how mindful parenting interventions (MPI) may support families of children with attention deficit hyperactivity disorder (ADHD). The aim of this study was to explore the potential barriers and enablers to parents' participation in a MPI from the perspectives of parents of children with ADHD and healthcare providers. MATERIALS AND METHODS: Thirteen parents of children with ADHD attended focus groups, and seven healthcare providers participated in semi-structured phone interviews. Transcripts of the focus groups and interviews were analysed using inductive thematic analysis. RESULTS: Three overarching themes related to potential barriers and enablers were identified: parent motivation and capacity to engage in a MPI, the need for multimodal and personalised delivery, and considerations for real-world program implementation. CONCLUSION: Parents of children with ADHD appear to require flexible, multimodal MPIs that consider parents' emotional experiences, priorities, and personal struggles.