Safety and efficacy of ibrutinib in combination with rituximab and lenalidomide in previously untreated follicular and marginal zone lymphoma: An open label, phase 2 study.

BACKGROUND: Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are indolent non-Hodgkin lymphomas (iNHL). Median survival for iNHL is approximately 20 years. Because standard treatments are not curative, patients often receive multiple lines of therapy with associated toxicity-rationally designed, combination therapies with curative potential are needed. The immunomodulatory drug lenalidomide was evaluated in combination with rituximab for the frontline treatment of FL in the phase 3 RELEVANCE study. Ibrutinib, an oral Bruton tyrosine kinase inhibitor, is active in NHL and was evaluated in combination with lenalidomide, rituximab, and ibrutinib (IRR) in a phase 1 study. METHODS: The authors conducted an open-label, phase 2 clinical trial of IRR for previously untreated FL and MZL. The primary end point was progression-free survival (PFS) at 24 months. RESULTS: This study included 48 participants with previously untreated FL grade 1-3a (N = 38), or MZL (N = 10). Participants received 12, 28-day cycles of lenalidomide (15 mg, days 1-21 cycle 1; 20 mg, cycles 2-12), rituximab (375 mg/m2 weekly in cycle 1; day 1 cycles 2-12), and ibrutinib 560 mg daily. With a median follow-up of 65.3 months, the estimated PFS at 24 months was 78.8% (95% confidence interval [CI], 68.0%-91.4%) and 60-month PFS was 59.7% (95% CI, 46.6%-76.4%). One death occurred unrelated to disease progression. Grade 3-4 adverse events were observed in 64.6%, including 50% with grade 3-4 rash. CONCLUSIONS: IRR is highly active as frontline therapy for FL and MZL. Compared to historical results with lenalidomide and rituximab, PFS is similar with higher grade 3-4 toxicity, particularly rash. The study was registered with ClinicalTrials.gov (NCT02532257).

Advance care planning and end-of-life care in a network of rural Western Australian hospitals.

OBJECTIVE: To provide a current perspective on end-of-life (EOL) care in regional Western Australia, with a particular focus on the final admission prior to death and the presence of documented advance care planning (ACP). DESIGN: Retrospective medical notes audit. SETTING: One regional hospital (including colocated hospice) and four small rural hospitals in the Great Southern region of Western Australia. PARTICIPANTS: Ninety recently deceased patients, who died in hospitals in the region. Fifty consecutive patients from the regional hospital and 10 consecutive patients from each of the four rural hospitals were included in the audit. INTERVENTIONS: A retrospective medical notes audit was undertaken. MAIN OUTCOME MEASURES: A 94-item audit tool assessed patient demographics, primary diagnosis, family support, status on admission and presence of documented ACP. Detailed items described the clinical care delivered during the final admission, including communication with family, referral to palliative care, transfers, medical investigations, medical treatments and use of EOL care pathways. RESULTS: Fifty-two per cent were women; median age was 82 years old. Forty per cent died of malignancy. Median length of stay was 7 days. Thirty-nine per cent had formal or informal ACP documented. Rural hospitals performed comparably with the regional hospital on all measures. CONCLUSIONS: This study provides benchmarking information that can assist other rural hospitals and suggests ongoing work on optimal methods of measuring quality in EOL care.

Obesity Is Associated with Driveline Infection of Left Ventricular Assist Devices.

In patients with left ventricular assist devices (LVADs), the association of driveline infection (DLI) and body mass index (BMI) remains controversial. The aim of this study was to explore a potential correlation between BMI and DLI in the LVAD patient population. A retrospective, single-center study evaluated patients who underwent LVAD implantation between May 2012 and July 2016. Driveline infection was evaluated per Interagency Registry for Mechanically Assisted Circulatory Support established criteria. Of 222 included patients, 80% were male, the average age was 55 years, and the main underlying heart failure diagnosis was nonischemic cardiomyopathy (56%). The majority of patients (65%) received LVAD as destination therapy and 35% as a bridge to transplantation. Average time-to-first DLI was 296 days after LVAD implantation. In comparison to non-DLI group (80%, N = 177), patients in DLI group (20%, N = 45) had a higher BMI (33.5 ± 8.3 kg/m in DLI group vs. 28.8 ± 7.5 kg/m in non-DLI group, p = 0.0003) and were younger (51 ± 12 years in DLI group vs. 56 ± 12 years in non-DLI group, p = 0.013). There was a significant correlation between BMI and DLI (p < 0.0001), and age was negatively correlated with DLI (p = 0.01). Analysis revealed no correlation between time-to-first DLI and BMI. Our data confirm that higher BMI is associated with increased prevalence of DLI in LVAD population, particularly in younger patients. Addressing excessive body weight in this patient cohort may significantly reduce DLI and thereby improve long-term outcomes.