A phase-II study of atezolizumab in combination with obinutuzumab or rituximab for relapsed or refractory mantle cell or marginal zone lymphoma or Waldenström's macroglobulinemia.

We report efficacy, safety and biomarker data from a phase-II study evaluating atezolizumab (eight 21-day cycle as induction therapy) in combination with obinutuzumab in patients with relapsed/refractory mantle cell lymphoma (MCL, n = 30) or Waldenström's macroglobulinemia (WM, n = 4), and in combination with rituximab in patients with marginal zone lymphoma (MZL, n = 21). All patients received atezolizumab monotherapy as maintenance for ≤10 cycles. Objective response rates at end of induction were 16.7% (MCL) and 42.9% (MZL), with no responses in WM. Median duration of response was 6.8 months (range 5.7-not estimable) for MCL and not reached for MZL. Treatment-emergent adverse events (TEAEs) occurred in 93.3%, 95.2% and 100% of MCL, MZL and WM patients, respectively. One fatal TEAE (pneumonia) occurred in each of the MCL and MZL groups. Biomarker analysis highlighted the importance of characterizing the immune environment to optimize efficacy of immunotherapy regimens.Trial registration details: EudraCT: 2016-003579-22.

Sublingual, transdermal and intravenous patient-controlled analgesia for acute post-operative pain: systematic literature review and mixed treatment comparison.

OBJECTIVE: To conduct a systematic literature review (SLR) and quantitative analysis to assess the comparative efficacy and safety of the sufentanil sublingual tablet system (SSTS) against other available patient controlled analgesia (PCA) options for post-operative analgesia. METHODS: An SLR was conducted for studies published between 2004 and 2016. Due to study heterogeneity, subgroup analyses were conducted controlling for differences in imputation methods for missing values, baseline pain severity, and type of surgery. Where sufficient data was available, a mixed treatment comparison (MTC) was performed. RESULTS: The MTC and subgroup analyses used 13 studies. In direct meta-analysis, there was a statistically significant difference in favor of SSTS compared with intravenous (IV) PCA (morphine) at 24 hours for the patient global assessment (PGA) scores of "good" or "excellent". For the Pain Intensity Score, there were numerical but not statistically significant differences in favor of the SSTS versus IV PCA (morphine) and the patient controlled transdermal system (PCTS) (fentanyl) in the MTC at 6 hours (standardized mean difference -0.27 [credible interval -2.78, 2.09] and -0.36 [-3.89, 3.03], respectively). The onset of pain relief was earlier with the SSTS versus IV PCA (morphine) as shown by the Pain Intensity Difference. Likewise, the onset was earlier compared with PCTS (fentanyl) where data was available. There was a significant difference in favor of SSTS compared with IV PCA (morphine) and with PCTS (fentanyl) for any adverse event, and numerical improvements for withdrawals due to adverse events. CONCLUSIONS: This meta-analysis shows that SSTS is an option for non-invasive management of moderate-to-severe post-operative pain which can be more effective, faster in onset and better tolerated than IV PCA (morphine) and PCTS (fentanyl).

[Nephrologist's behaviours and perceptions on sideropenic anemia's diagnosis and treatment for conservative phase nephropatic patient intolerant or not responding to oral iron therapy]. / Approccio clinico del nefrologo alla diagnosi e al trattamento dell'anemia sideropenica in pazienti con CKD non-dialitica.

INTRODUCTION. The objective of this survey was to describe the nephrologists attitude on the diagnosis and treatment of patients with non-dialysis Chronic Kidney Disease (CKD stages 3, 4 and 5), with iron deficiency anemia and no response/intolerance to oral iron therapy. Furthermore, this survey describes the nephrologists view about the impact of lack of anemia correction on patient health, as well as the influence of organization and management of nephrological centers on IV iron management. MATERIALS AND METHODS. 60 nephrologists were interviewed via web by using an interactive simulation that investigates nephrologists clinical and therapeutic approach on 3 different types of patients; subsequently, a questionnaire was administered with in-deeper questions. RESULTS. Regarding the first virtual patient, 64% of nephrologists still choose oral iron, while IV iron was chosen by 16% of them. 36% opted for ESA. For the other two virtual patients the most selected treatments were combinations of oral iron + ESA (42% and 36%) or IV iron + ESA (21% and 38%), respectively. According to what was perceived by nephrologists, issues related to IV iron are: patient discomfort due to frequent hospital transfers for IV administration (50%), inadequate center organization (48%), fear of damaging the venous tree (40%). CONCLUSIONS. Half of the nephrologists stated they are unsatisfied with available iron therapies. Difficult therapy management and restrictions of health structure were identified as barriers to the prescription of IV iron therapy. A smaller number of administrations and less free-iron toxicity are expected from nephrologists from the new iron preparations for the management of iron deficiency in patients not responding/intolerant to oral iron therapy.