Summary Background Patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL) have an unfavourable prognosis with few treatment options. Polatuzumab vedotin is an antibody–drug conjugate ...containing an anti-CD79B monoclonal antibody conjugated to the microtubule-disrupting agent monomethyl auristatin E. We aimed to assess the safety and clinical activity of polatuzumab vedotin in relapsed or refractory B-cell NHL and chronic lymphocytic leukaemia (CLL). Methods In this phase 1, multicentre, open-label study, we enrolled patients with documented NHL or CLL expected to express CD79B (confirmation of CD79B expression was not required) and for whom no suitable therapy of curative intent or higher priority existed from 13 centres. The primary endpoints of the study were to assess safety and tolerability, determine the maximum tolerated dose, and identify the recommended phase 2 dose of polatuzumab vedotin as a single agent and in combination with rituximab. A 3 + 3 dose-escalation design was used in which we treated patients with polatuzumab vedotin (0·1–2·4 mg/kg every 21 days) in separate dose-escalation cohorts for NHL and CLL. After determination of the recommended phase 2 dose, we enrolled patients with relapsed or refractory diffuse large B-cell lymphoma and relapsed or refractory indolent NHL into indication-specific cohorts. We also enrolled patients with relapsed or refractory NHL into an additional cohort to assess the feasibility of the combination of polatuzumab vedotin and rituximab 375 mg/m2 . Patients who received any dose of polatuzumab vedotin were available for safety analyses. This study is registered with ClinicalTrials.gov , number NCT01290549. Findings Between March 21, 2011, and Nov 30, 2012, we enrolled 95 patients (34 to the NHL dose-escalation cohort, 18 to the CLL dose-escalation cohort, 34 with NHL to the expansion cohort at the recommended phase 2 dose, and nine with NHL to the rituximab combination cohort; no expansion cohort of CLL was started due to lack of activity in the dose-escalation cohort). The recommended phase 2 dose in NHL was 2·4 mg/kg as a single agent and in combination with rituximab; the maximum tolerated dose in CLL was 1·0 mg/kg as a result of dose-limiting toxic effects reported in two of five patients given 1·8 mg/kg. Grade 3–4 adverse events were reported in 26 (58%) of 45 patients with NHL treated at the single-agent recommended phase 2 dose, and the most common grade 3–4 adverse events were neutropenia (18 40% of 45), anaemia (five 11%), and peripheral sensory neuropathy (four 9%). Serious adverse events were reported in 17 (38%) of 45 patients, and included diarrhoea (two patients), lung infection (two patients), disease progression (two patients), and lung disorder (two patients). Seven (77%) of nine patients in the rituximab combination cohort had a grade 3–4 adverse event, with neutropenia (five 56%), anaemia (two 22%), and febrile neutropenia (two 22%) reported in more than one patient. 11 (12%) of 95 patients died during the study: eight with relapsed or refractory diffuse large B-cell lymphoma (due to progressive disease in four patients, infections in three patients two treatment related, and treatment-related worsening ascites in one patient) and three with relapsed or refractory CLL (due to progressive disease, pulmonary infection, and pneumonia; none thought to be treatment-related). At the recommended phase 2 dose, objective responses were noted in 23 of 42 activity-evaluable patients with NHL given single-agent polatuzumab vedotin (14 of 25 with diffuse large B-cell lymphoma, seven of 15 with indolent NHL, and two with mantle-cell lymphoma) and seven of nine patients treated with polatuzumab vedotin combined with rituximab. No objective responses were observed in patients with CLL. Interpretation Polatuzumab vedotin has an acceptable safety and tolerability profile in patients with NHL but not in those with CLL. Its clinical activity should be further assessed in NHL. Funding Genentech.
To understand the patient-influenced activities and characteristics associated with return to a single postacute care transitional care clinic visit in a cohort of patients cared for at the test ...health system site of the larger Comprehensive Post-Acute Stroke Services (COMPASS) cluster randomized trial.
Retrospective cohort.
A large health system.
Patients discharged directly home between June 2016 and June 2018 after sustaining a stroke who did not receive formal inpatient rehabilitation services while being cared for in a single comprehensive stroke center, defined as a center that meet standards to rapidly diagnose and treat the most complex stroke cases.
Study participants had the opportunity to participate in a (1) 2-day call, (2) comprehensive care transitions clinic visit, and (3) individualized care plan.
Patient participation in a single postacute care comprehensive care transitions visit, ideally completed within 7-14 calendar days post discharge vs not attending this visit. Care transition visits are where the responsibility for preventive care, other services, and posthospital follow-up are transitioned to outpatient providers.
Among 1300 eligible patients (mean age 64.8 years; 45% female; 25.4% nonwhite; 9.7% uninsured), 95.7% had follow-up clinic visits scheduled before discharge, 22.6% received home health referrals before discharge, 60.2% completed the 2-day call, and 63.2% attended the COMPASS visit. Among attendees, 33.2% attended by day 14, 71.3% attended within 30 days, and 28.7% attended after day 30. The median driving distance to the COMPASS visit was 45.9 miles or 73.9 km. Odds of visit attendance were higher if COMPASS 2-day follow up calls were completed, if follow-up clinic appointments were scheduled before discharge, if the patient had a primary care provider, and if the patients experienced a stroke vs a transient ischemic attack. Additionally, when we used the number of referrals at hospital discharge for different types of outpatient therapy as a surrogate marker of poststroke impairment, patients having no therapy referrals (milder to no impairments) had lower odds of attending the COMPASS visit than those with 1 therapy referral. Likewise, those with more than 1 referral were also less likely to attend the COMPASS visit.
This analysis highlights that scheduling visits at discharge and completing timely telephone follow-up shortly after discharge may lead to greater adherence to in-person clinic follow-up after stroke.
PDF