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.
Abstract Purpose We evaluated receipt of cervical cancer screening in a national sample of 34,213 women veterans using Veteran Health Administration facilities between 2003 and 2007 and diagnosed ...with 1) posttraumatic stress disorder (PTSD), or 2) depression, or 3) no psychiatric illness. Methods Our study featured a cross-sectional design in which logistic regression analyses compared receipt of recommended cervical cancer screening for all three diagnostic groups. Results Cervical cancer screening rates varied minimally by diagnostic group: 77% of women with PTSD versus 75% with depression versus 75% without psychiatric illness were screened during the study observation period ( p < .001). However, primary care use was associated with differential odds of screening in women with versus without psychiatric illness (PTSD or depression), even after adjustment for age, income and physical comorbidities (Wald Chi-square (2): 126.59; p < .0001). Specifically, among low users of primary care services, women with PTSD or depression were more likely than those with no psychiatric diagnoses to receive screening. Among high users of primary care services, they were less likely to receive screening. Conclusion Psychiatric illness (PTSD or depression) had little to no effect on receipt of cervical cancer screening. Our finding that high use of primary care services was not associated with comparable odds of screening in women with versus without psychiatric illness suggests that providers caring for women with PTSD or depression and high use of primary care services should be especially attentive to their preventive healthcare needs.
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