Ibrutinib plus RICE or RVICI for relapsed/refractory mature B-cell non-Hodgkin lymphoma in children and young adults:SPARKLE trial

Part 1 results of the open-label, randomized, global phase 3 SPARKLE trial supported continued assessment of ibrutinib with either modified rituximab, ifosfamide, carboplatin, and etoposide (RICE) or rituximab, vincristine, ifosfamide, carboplatin, idarubicin, and dexamethasone (RVICI) in pediatric patients with relapsed/refractory (R/R) mature B-cell non-Hodgkin lymphoma (B-NHL). We report final results of Part 2 evaluating the efficacy of ibrutinib plus RICE or RVICI vs RICE/RVICI alone. Patients aged 1 to 30 years (initial diagnosis \u3c18 years) were randomized 2:1 to receive ibrutinib with or without RICE/RVICI. Primary endpoint was event-free survival (EFS) based on independent committee-confirmed events. Fifty-one patients were enrolled. Median age was 15 years; Burkitt lymphoma, Burkitt leukemia, and Burkitt-like lymphoma (total: 45%) and diffuse large B-cell lymphoma/primary mediastinal B-cell lymphoma (51%) were the most common subtypes. At the preplanned interim analysis, median EFS was 6.1 vs 7.0 months with ibrutinib plus RICE/RVICI vs RICE/RVICI, respectively (hazard ratio, 0.9; 90% confidence interval, 0.5-1.6; P = .387); further enrollment was ceased. With ibrutinib plus RICE/RVICI vs RICE/RVICI, median overall survival was 14.1 vs 11.1 months, overall response rate was 69% vs 81%, and 46% vs 44% proceeded to stem cell transplantation. In both treatment arms, 100% of patients experienced grade ≥3 treatment-emergent adverse events. No EFS benefit was seen with ibrutinib. Salvage was generally poor in patients who received prior rituximab, regardless of treatment arm. No new safety signals were observed. Ibrutinib exposure in pediatric patients fell within the target range of exposure in adults. Trial is registered on www.clinicaltrials.gov (NCT02703272)

Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue

Evolution of the late Pleistocene Mojanda-Fuya Fuya volcanic complex (Ecuador), by progressive adakitic involvement in mantle magma sources

International audienceThe Mojanda-Fuya Fuya Volcanic Complex consists of two nearby volcanoes, Mojanda and Fuya Fuya. The older one, Mojanda volcano (0.6 to 0.2 Ma), was first constructed by andesites and high-silica andesites forming a large stratovolcano (Lower Mojanda). This edifice was capped by a basaltic andesite and andesitic cone (Upper Mojanda), which collapsed later to form a 3-km-wide summit caldera, after large phreatomagmatic eruptions. The Lower Fuya Fuya edifice was constructed by the extrusion of viscous Si-rich andesitic lavas and dacitic domes, and the emission of a thick sequence of pyroclastic-flow and fallout deposits which include two voluminous rhyolitic layers. An intermediate construction phase at Fuya Fuya is represented by a mainly effusive cone, andesitic in composition (San Bartolo edifice), the construction of which was interrupted by a major sector collapse in the Late Pleistocene. Finally, a complex of thick siliceous lavas and domes was emplaced within the avalanche amphitheatre, forming the Upper Fuya Fuya volcanic centre. This paper shows that the general evolution from an effusive to an explosive eruptive style is related to a progressive adakitic contribution to the magma source. Although all the rocks of the complex are included in the medium-K field of continental arcs, the Fuya Fuya suite (61-75 wt.% SiO2) shows depletion in Y and HREE and high Sr/Y and La/Yb values, compared to the less silicic Mojanda suite (55-66.5 wt.% SiO2). The Mojanda calc-alkaline suite was generated by partial melting of an adakite-metasomatised mantle source that left a residue with 2% garnet, followed by fractional crystallization of dominant plagioclase + pyroxene + olivine at shallow, intra-crustal depths. For Fuya Fuya, geochemical and mineralogical data suggest either (1) partial melting of a similar metasomatised mantle with more garnet in the residue (4%), followed by fractional crystallization involving plagioclase, amphibole and pyroxene, or (2) mixing of mafic mantle-derived magma from the Mojanda suite and slab melts, followed by the same fractional crystallization process

Timbre description of the sound of air-treatment systems for predicting acoustic comfort

International audienceThis study aims at defining reliable acoustic cues for the measure, characterization and prediction of the acoustic comfort of air-treatment systems (ATS). To meet customers' expectations, industrial products tend increasingly to follow a process of "sound design". In this process, the perceptual evaluation of sound quality is a necessary step to define acoustic specifications. In this context, this study aims at defining the main perceptual attributes of the sound of air-treatment systems in order to predict users preferences. The timbre space of a sound dataset extracted from a large recording database was thus identified through a similarity experiment where participants were asked to rate the resemblance between each pair of sounds. The results of this experiment were analyzed with a Multidimensional Scaling (MDS) method in order to extract the main perceptual attributes. Finally, these attributes were linked to relevant audio features through a regression method in order to define a reliable computable metric of acoustic comfort. This study was conducted through the Vaicteur Air2 project supported by OSEO

Antisana volcano: A representative andesitic volcano of the eastern cordillera of Ecuador: Petrography, chemistry, tephra and glacial stratigraphy

International audienceAntisana volcano is representative of many active andesitic strato-volcanoes of Pleistocene age in Ecuador's Eastern Cordillera. This study represents the first modern geological and volcanological investigation of Antisana since the late 1890's; it also summarizes the present geochemical understanding of its genesis. The volcano's development includes the formation and destruction of two older edifices (Antisana I and II) during some 400 + ka. Antisana II suffered a sector collapse about 15,000 years ago which was followed by the birth and growth of Antisana III. During its short life Antisana III has generated ≥50 eruptions of small to medium intensity, often associated with andesitic to dacitic lava flows and tephra, as well as with late Pleistocene and Holocene glacial advances. Throughout its long history Antisana's lavas have been characterized by a persistent mineral assemblage, consisting of 30–40 vol% phenocrysts of plagioclase, both clino- and orthopyroxene, and Fe-Ti oxides, with rare occurrences of olivine or amphibole, frequently in a microcrystalline to glassy matrix. This uniformity occurs despite the magma's progressive chemical evolution over ≥400 ka from early basic andesites (53–58 wt% SiO2) to intermediate and Si-rich andesites (58–62% SiO2), and recently to dacites (63–67% SiO2). Chemical diagrams suggest that crystal fractionation was the most likely magmatic process of evolution. The exception to this slowly evolving history was the short-lived emission at ∼210 ka of the Cuyuja lavas from Antisana II that generated a 73 km long andesitic lava flow. Contrasting with Antisana's general magmatic trend, Cuyuja lava (∼11 km3) is a high-Mg andesite with unusually high concentrations of incompatible elements. Antisana developed within the Chacana caldera complex, a large active siliceous center that began ∼3 Ma ago, however its lavas are chemically distinct from coeval lavas of Chacana