Efficacy comparison of tisagenlecleucel vs usual care in patients with relapsed or refractory follicular lymphoma.

The ELARA trial indicates tisagenlecleucel (tisa-cel) is an effective anti-CD19 chimeric antigen receptor T-cell therapy for relapsed or refractory follicular lymphoma (r/r FL). As ELARA is a single-arm trial, this study compares tisa-cel outcomes from the ELARA trial with usual care from a real-world cohort. ELARA enrolled 98 patients as of 29 March 2021 (median follow-up: 15 months from enrollment). Usual care data were obtained from ReCORD-FL, a global retrospective study of patients with r/r FL, who met similar eligibility criteria to ELARA. With a data cutoff date of 31 December 2020, 187 patients with ≥2 preceding treatment lines were included in the ReCORD-FL (median follow-up: 57 months from third-line) study. An indirect treatment comparison was performed for 97 patients from the ELARA trial and 143 patients from the ReCORD-FL study with no missing data on baseline factors. The line of therapy for which outcomes were assessed was selected or matched between cohorts using propensity score modeling. After baseline factor adjustment via weighting by odds, complete response rate (CRR; 95% confidence interval) was 69.1% (59.8%-78.3%) for tisa-cel vs. 37.3% (26.4%-48.3%) for usual care; overall response rate was 85.6% (78.7%-92.5%) vs. 63.6% (52.5%-74.7%). Kaplan-Meier probability of being progression/event-free at 12 months was 70.5% (61.4%-79.7%) for tisa-cel vs. 51.9% (40.6%-63.3%) for usual care, with hazard ratio (HR)=0.60 (0.34-0.86); 12-month overall survival was 96.6% (92.9%-100%) vs. 71.7% (61.2%-82.2%), with HR=0.2 (0.02-0.38). In conclusion, tisa-cel was associated with a 1.9-fold higher complete response rate and a 1.4-fold higher rate of being progression or event free at 12 months vs usual care, as well as a death risk reduction of 80%. The findings provide additional evidence on the benefit of tisa-cel in patients with r/r FL after ≥2 treatment lines. This trial was registered at www.clinicaltrials.gov as NCT03568461.

Immune analysis of lymph nodes in relation to the presence or absence of tumor infiltrating lymphocytes in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with unmet medical needs. Several studies have proved that high levels of tumor infiltrating lymphocytes (TILs) at diagnosis of TNBC confer better prognosis and patients respond better to specific chemotherapies. Nonetheless, current evidence suggests that only 15% of TNBC patients have very high levels of TILs, and another 15% lacks TILs. One possible reason to explain why patients have low TILs at diagnosis is that lymphocytes might be deactivated by an immune checkpoint in local lymph nodes, provoking their retention in there as they are unresponsive to other immune stimuli. We have identified 15 high TILs (≥50%) and 20 low TILs (≤5%) TNBC patients with localised tumour (T1c-T2N0M0) and compared the protein expression of five immune checkpoints in lymph nodes. We have also performed a customised 50-immune gene NanoString expression panel, the NanoString 360 Breast Cancer panel, and whole exome sequencing for mutation and neoantigen load analyses. In low TILs, we observed higher expression of CTLA-4 in local lymph nodes, which could explain why lymphocytes get retained in there and do not migrate to tumour. These patients have also higher neoantigen load and higher expression of B7.H3 and B7.H4 in the tumour. In high TILs, we observed more PD-L1+ tumour cells and more expanded humoral response. These results could provide a strategy to revert low tumour immune infiltration at diagnosis of TNBC, improving their prognosis.

Desenvolvimento e aceitação de pães sem glúten com farinhas de resíduos de abóbora (cucurbita moschata) / Development and acceptance of gluten-free breads with pumpkin waste flour (cucurbita moschata)

Introdução: A doença celíaca é caracterizada como uma enteropatia autoimune, desencadeada pela ingestão do glúten. A adição de partes não convencionais dos vegetais propicia produtos com melhor qualidade nutricional. Diversos nutrientes são encontrados na semente de abóbora, em especial lipídios, proteínas e fibras alimentares. Na casca têm destaque as fibras, ácido ascórbico e cálcio. Objetivo: Desenvolver e avaliar a aceitabilidade sensorial de formulações de pães sem glúten com diferentes teores de farinha da semente de abóbora e farinha da casca de abóbora, bem como determinar a composição físico-química das farinhas. Material e Métodos: Após a elaboração das farinhas, foram preparadas quatro formulações de pães adicionadas de farinha de semente e casca de abóbora. Determinou-se a composição físico-química nas farinhas e foi realizada análise sensorial dos pães com 50 provadores não treinados. Resultados: A farinha de semente de abóbora apresentou maiores teores de lipídios, proteínas e fibras, enquanto maiores teores de umidade, cinzas e carboidratos foram constatados na farinha de casca de abóbora, sendo estatisticamente significativos. De acordo com a análise da composição nutricional dos pães, as formulações adicionadas de farinha de semente apresentaram teores maiores de proteínas, lipídeos e fibras do que as adicionadas com farinha da casca. Na análise de aceitabilidade não houve associação estatística significativa entre as formulações com diferentes percentuais das farinhas. Os pães adicionados com farinha de semente obtiveram melhores resultados no teste de intenção de compra quando comparados aos pães com farinha da casca. Conclusão: As farinhas elaboradas mostram-se viáveis para aplicação em produtos de panificação, pois aumentam a qualidade nutricional dos produtos. Apesar disso, fazem-se necessários ajustes para que a farinha da casca de abóbora tenha melhor aceitação por parte dos consumidores.

Introduction: Celiac disease is characterized as an autoimmune enteropathy, triggered by the ingestion of gluten. The addition of unconventional parts of the vegetables provides products with better nutritional quality. Various nutrients are found in pumpkin seed, especially lipids, proteins and dietary fibers, as well as fiber, ascorbic acid and calcium in the bark. Objective: Develop and evaluate the sensory acceptability of gluten-free bread formulations with different contents of pumpkin seed flour and pumpkin peel flour, as well as determine the physicochemical composition of the flour. Material and Methods: After the flour was prepared, four formulations of breads added were prepared from seed flour and pumpkin peel. The physico-chemical composition in the flours was determined and sensory analysis of the loaves was performed with 50 untrained tasters. Results: Pumpkin seed meal presented higher levels of lipids, proteins and fibers, while higher levels of moisture, ashes and carbohydrates were observed in the pumpkin peel meal, being statistically significant. According to the analysis of the nutritional composition of the breads, the added formulations of the seed meals had higher protein, lipid and fiber contents than those added with rind flour. In the analysis of acceptability, there was no significant statistical association between the formulations with different percentages of the flours. The breads added with seed flour obtained better results in the test of intention to buy when compared to the bread with flour of the bark. Conclusion: The elaborated flours are viable for application in bakery products, as they increase the nutritional products quality. In spite of this, adjustments are necessary so that the flour of the pumpkin peel is better accepted by the consumers.