PD-L1 expression predicts efficacy in the phase II SPiReL trial with MVP-S, pembrolizumab, and low-dose CPA in R/R DLBCL.

BACKGROUND: Patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) have limited treatment options. METHODS: R/R DLBCL patients, who were mostly ineligible for ASCT due to age or comorbidities, were treated with maveropepimut-S (MVP-S, previously DPX-Survivac) a survivin directed T cell educating therapy, pembrolizumab, and intermittent low-dose cyclophosphamide. FINDINGS: We identified, using univariate analysis, a subset of patients with enhanced ORR, PFS and DOR. Patients with baseline CD20+/PD-L1 expression had an ORR of 46% (6/13) and the disease control rate was 10/13 (77%). The PFS and OS of the positive CD20+/PD-L1 patients were 7.1 months and 17.4 months, whereas in the intent-to-treat (ITT) population of 25 enrolled patients, the ORR was 28% (7/25), median PFS and OS were 4.2 months and 10.1 months respectively. A total of 6/7 clinical responders occurred in CD20+/PD-L1 patients. The regimen was well-tolerated, requiring only minor dose modifications and one discontinuation. Grade 1 or 2 injection site reactions occurred in 14/25, (56%). Statistically significant associations were also seen between PFS and; injection site reactions; and ELISpot response to survivin peptides, both identifying the mechanistic importance of specific immune responses to survivin. INTERPRETATION: This immunotherapy combination was found to be active and safe in this clinically challenging patient population.

Intensity of survivin expression linked to features of aggressive relapsed/refractory diffuse large B-cell lymphoma.

SPiReL is a phase II clinical trial evaluating combination immunotherapy, pembrolizumab and cyclophosphamide, with maveropepimut-S, in survivin-expressing relapsed/refractory (R/R) Diffuse Large B Cell Lymphoma (DLBCL). We describe baseline tumor survivin expression and associations with clinico-pathological variables in 25 participants. The median number of survivin-expressing cells was 99%, and the intensity of survivin expression within tumors was heterogeneous by semi-quantitative immunohistochemistry assessment. Tumors with higher numbers of cells expressing 2+/3+ survivin were associated with characteristics of poor outcome, (Lactate dehydrogenase and cell-of-origin). Greater total baseline tumor area was associated with lower proportions of 1+ cells and greater proportions of 2+/3+ cells. High intensity survivin expression is associated with aggressive clinical features supporting a pathobiological role in R/R DLBCL. Future prognostic models incorporating survivin as a clinical biomarker require assessment of intensity, overall expression and should include potential threshold effects of survivin in DLBCL pathobiology.

Introduction of pharmaceutical expertise in a palliative care team in Sweden.

OBJECTIVE: This paper presents for the first time the inclusion of dispensing pharmacists, a special group of pharmacy professionals, in a Swedish palliative care team. It also presents the drug stock management in the medication room of the clinical area and the improvement of drug logistics. In addition to a dispensing pharmacist, a pharmacist was included in this part of the project as well. SETTING: The palliative care team at ASIH Långbro Park, Sweden. METHOD: The intervention with the dispensing pharmacists as new members of the interdisciplinary palliative team was evaluated by a questionnaire to the staff. An inventory of the different drugs in stock was performed in March 2006 and in April 2007, respectively. The inventory turnover rate was determined and the drug consumption for the last 6 months of 2005 and 2006, respectively, was also analysed. MAIN OUTCOME MEASURES: The questionnaire used rating scales allowing participants to rate the questions/statements. The number of different drugs and drug packages in stock were recorded during the inventories. Drug costs were calculated and the inventory turnover rate was determined by dividing the annual cost of drugs by the value of the inventory. Drug consumption was analysed using the Xplain statistical programme, a statistical tool from Apoteket AB. RESULTS: The overall impression of the dispensing pharmacists was positive. The staff reported advantages in having a dispensing pharmacist present at ASIH not only for the drug logistics, but also for drug-related queries. The inventory of the drug stock and the drug-handling process resulted in a 14% reduction of product numbers and a 36% reduction in the tied-up capital for drugs in stock. The inventory turnover rate increased from 6.7 to 9.5. A 7% reduction of medication costs was also observed when comparing the last 6 months of 2006 with the costs in 2005. CONCLUSION: The principal result of this project is that inclusion of pharmaceutical expertise on a palliative care team can be a valuable asset for the team in pharmaceutical issues and of great benefit for stock management, including cost savings and improvement of drug logistics.

Formulating goals in occupational therapy: State of the art in Switzerland.

BACKGROUND: The contemporary occupational therapy literature suggests that different quality criteria exist for setting goals in occupational therapy: a focus on occupation; a link to the International Classification of Functioning, Disability, and Health (ICF); and adherence to the SMART recommendations, which advises goals to be specific, measurable, agreed, realistic, and timed. AIM: To identify the extent to which Swiss occupational therapists (OTs) adhere to the criteria cited above. MATERIAL: A total of 1,129 goals formulated with the Goal Attainment Scale (GAS) collected in 2008. RESULTS: In slightly more than half the investigated cases at least one goal addressed an aspect of occupation. Nearly two-thirds of the goals related to the ICF component "activity and participation". Nearly 90% of the goals were specific, measurable, and/or realistic. CONCLUSIONS: Goals mirror, to some extent, what is done in everyday practice. Several influences on goal formulations of OTs were identified, including the practice models traditionally used in different specialist fields; the cultural contexts in which OTs were trained; and the legal framework that obliges OTs to formulate their goals in a certain way in order to obtain funding for their services. SIGNIFICANCE: Based on these results evidence-based products have been developed (a further education course; written recommendations for practice).