The academic point-of-care anti-CD19 chimeric antigen receptor T-cell product varnimcabtagene autoleucel (ARI-0001 cells) shows efficacy and safety in the treatment of relapsed/refractory B-cell non-Hodgkin lymphoma.

Varnimcabtagene autoleucel (var-cel) is an academic anti-CD19 chimeric antigen receptor (CAR) product used for the treatment of non-Hodgkin lymphoma (NHL) in the CART19-BE-01 trial. Here we report updated outcomes of patients with NHL treated with var-cel. B-cell recovery was compared with patients with acute lymphoblastic leukaemia (ALL). Forty-five patients with NHL were treated. Cytokine release syndrome (any grade) occurred in 84% of patients (4% grade ≥3) and neurotoxicity in 7% (2% grade ≥3). The objective response rate was 73% at Day +100, and the 3-year duration of response was 56%. The 3-year progression-free and overall survival were 40% and 52% respectively. High lactate dehydrogenase was the only covariate with an impact on progression-free survival. The 3-year incidence of B-cell recovery was lower in patients with NHL compared to ALL (25% vs. 60%). In conclusion, in patients with NHL, the toxicity of var-cel was manageable, while B-cell recovery was significantly prolonged compared to ALL. This trial was registered as NCT03144583.

Results of ARI-0001 CART19 cell therapy in patients with relapsed/refractory CD19-positive acute lymphoblastic leukemia with isolated extramedullary disease.

We evaluated outcomes of 18 patients with isolated extramedullary disease (iEMD) relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) treated with the CD19-directed CAR T cells ARI-0001 in two centers (adult and pediatric), including patients treated in the CART19-BE-01 trial and the consecutive compassionate use program. iEMD was detected by PET-CT in 78% (14/18), and/or by cerebrospinal fluid analysis in 28% (5/18). Patients received cyclophosphamide and fludarabine followed by 1 × 106 ARI-0001 cells/kg, initially as a single dose (first patient) and later split into three fractions (10%, 30%, and 60%). Cytokine release syndrome (CRS) occurred in 50% (9/18) of patients, with no cases of grade ≥3 CRS, and 1 case (6%) of grade 1 neurotoxicity. Tocilizumab was used in 6% of patients (1/18). Procedure-related mortality was 0% at 2 years. Objective responses were seen in 94% (95% confidence interval [CI]: 73%-99%) of patients, with complete responses (CR) seen in 78% (95% CI: 52%-94%) of them. Progression-free and overall survival were 49% (95% CI: 30%-79%) and 61% (95% CI: 40%-92%) at 2 years. In conclusion, the use of ARI-0001 cells in patients with R/R ALL and iEMD was associated with a safety and efficacy profile that is comparable with what is observed in patients with marrow involvement and in line with other CART19 products.

Integrated Management of Pain in Advanced Dementia.

AIM: Develop and evaluate the implementation of a protocol for comprehensive management of pain in advanced dementia. METHOD: Quasi-experimental study carried out between September 2015 and May 2016 in an acute geriatric unit. Following development of the protocol and nurse training, 22 participants were recruited through consecutive sampling to form the intervention group (IG). Pain assessment was performed using the Pain Assessment in Advanced Dementia Spanish version (PAINAD-Sp) instrument and by nurse report-rating using the Numeric Rating Scale (NRS) and control group, with pain assessment through nurse-report using an NRS. Interventions carried out following perception of pain were done according to the actions algorithm created for this purpose. Follow-up was carried out daily during the hospital stay. RESULTS: Some 98% of the actions were performed correctly following the protocol. All (100%) of patients had a scheduled prescription for analgesics. Significant differences between mean pain scores at admission and discharge were found through PAINAD-Sp using a Wilcoxon sign test of -2.9543 (p = .004). Analysis of pain perception scores revealed a statistically significant positive correlation between the number of nonpharmacological actions performed and the pain score values obtained in the IG (rho Spearman: 0.617, p < .001) and the control group (rho Spearman: 0.922, p < .001). A high correlation was also observed in the IG between assessments conducted using PAINAD-Sp and NRS (intraclass correlation coefficient: 0.921). CONCLUSIONS: The implementation of an agreed-upon, standardized protocol for comprehensive pain management in advanced dementia, including nurse training, leads to systematic application of all the protocol stages, and therefore better pain management.

Advanced dementia pain management protocols. / Protocolos de gestión del dolor en demencia avanzada.

Pain management in advanced dementia is complex because of neurological deficits present in these patients, and nurses are directly responsible for providing interventions for the evaluation, management and relief of pain for people suffering from this health problem. In order to facilitate and help decision-makers, pain experts recommend the use of standardized protocols to guide pain management, but in Spain, comprehensive pain management protocols have not yet been developed for advanced dementia. This article reflects the need for an integrated management of pain in advanced dementia. From the review and analysis of the most current and relevant studies in the literature, we performed an approximation of the scales for the determination of pain in these patients, with the observational scale PAINAD being the most recommended for the hospital setting. In addition, we provide an overview for comprehensive management of pain in advanced dementia through the conceptual framework «a hierarchy of pain assessment techniques by McCaffery and Pasero¼ for the development and implementation of standardized protocols, including a four-phase cyclical process (evaluation, planning/performance, revaluation and recording), which can facilitate the correct management of pain in these patients.

[Quality of diagnosis information given to terminal cancer patients]. / Calidad de la información sobre el diagnóstico al paciente oncológico terminal.

AIM: To determine the information that terminal cancer patients have about their diagnosis, identifying key words used, and quantifying the conspiracy of silence. METHOD: A cross-sectional, analytical study was conducted by reviewing the hospice support team data base which contains the medical history and a semi-structured interview with terminal cancer patients in the first visit to the hospice. Demographic and socioeconomic data was collected, as well as relevant clinical information (diagnosis, prevalent symptoms, number of symptoms, patient functionality, QoL, information given, and words used). RESULTS: Out of total of sample of 723 records, 77.87% (95% CI: 74.70-80.74) of the patients were properly informed about their diagnosis. The most used words were cancer in 26% of the patients, tumour in 51.59%, and for the remaining 10.65%, the word inflammation was used. Statistically significant differences of information were found between sexes, age, types of cancer, and hospital ward. CONCLUSIONS: Terminal cancer patients have knowledge on their diagnosis, suggesting that the conspiracy of silence is present to a lesser extent. This knowledge is transmitted using different words and with euphemisms.