Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma

Daratumumab, a human CD38 immunoglobulin G1 kappa (IgG1κ) monoclonal antibody, has activity as monotherapy in multiple myeloma (MM). This phase 1/2 study investigated daratumumab plus lenalidomide/dexamethasone in refractory and relapsed/refractory MM. Part 1 (dose escalation) evaluated 4 daratumumab doses plus lenalidomide (25 mg/day orally on days 1-21 of each cycle) and dexamethasone (40 mg/week). Part 2 (dose expansion) evaluated daratumumab at the recommended phase 2 dose (RP2D) plus lenalidomide/dexamethasone. Safety, efficacy, pharmacokinetics, immunogenicity, and accelerated daratumumab infusions were studied. In part 1 (13 patients), no dose-limiting toxicities were observed, and 16 mg/kg was selected as the R2PD. In part 2 (32 patients), median time since diagnosis was 3.2 years, with a median of 2 prior therapies (range, 1-3 prior therapies), including proteasome inhibitors (91%), alkylating agents (91%), autologous stem cell transplantation (78%), thalidomide (44%), and lenalidomide (34%); 22% of patients were refractory to the last line of therapy. Grade 3 to 4 adverse events (≥5%) included neutropenia, thrombocytopenia, and anemia. In part 2, infusion-related reactions (IRRs) occurred in 18 patients (56%); most were grade ≤2 (grade 3, 6.3%). IRRs predominantly occurred during first infusions and were more common during accelerated infusions. In part 2 (median follow-up of 15.6 months), overall response rate was 81%, with 8 stringent complete responses (25%), 3 complete responses (9%), and 9 very good partial responses (28%). Eighteen-month progression-free and overall survival rates were 72% (95% confidence interval, 51.7-85.0) and 90% (95% confidence interval, 73.1-96.8), respectively. Daratumumab plus lenalidomide/dexamethasone resulted in rapid, deep, durable responses. The combination was well tolerated and consistent with the safety profiles observed with lenalidomide/dexamethasone or daratumumab monotherapy. This trial was registered at www.clinicaltrials.gov as #NCT01615029

Key Biochemical Attributes to Assess Soil Ecosystem Sustainability

Soil is not a renewable resource, at least within the human timescale. In general, any anthropic exploitation of soils tends to disturb or divert them from a more “natural” development which, by definition, represents the best comparison term for measuring the relative shift from soil sustainability. The continuous degradation of soil health and quality due to abuse of land potentiality or intensive management occurs since decades. Soil microbiota, being ‘the biological engine of the Earth’, provides pivotal services in the soil ecosystem functioning. Hence, management practices protecting soil microbial diversity and resilience, should be pursued. Besides, any abnormal change in rate of innumerable soil biochemical processes, as mediated by microbial communities, may constitute early and sensitive warning of soil homeostasis alteration and, therefore, diagnoses a possible risk for soil sustainability. Among the vastness of soil biochemical processes and related attributes (bioindicators) potentially able to assess the sustainable use of soils, those related to mineralisation-immobilisation of major nutrients (C and N), including enzyme activity (functioning) and composition (community diversity) of microbial biomass, have paramount importance due to their centrality in soil metabolism. In this chapter we have compared, under various pedoclimates, the impact of different agricultural factors (fertilisation, tillage, etc.) under either intensive and sustainable managements on soil microbial community diversity and functioning by both classical and molecular soil quality indicators, in order to outline the most reliable soil biochemical attributes for assessing risky shifts from soil sustainability

Microalgal Biomass of Industrial Interest: Methods of Characterization

International audienceMicroalgae represent a new source of biomass for many applications. The advantage of microalgae over higher plants is their high productivities. The photoautotrophic microalgae include all photosynthetic microorganisms, i.e. Cyanobacteria (prokaryotes) or microalgae (eukaryotes). These microorganisms are characterized by a large biodiversity and chimiodiversity. Then, the analysis of microalgal and cyanobacterial biomass often needs specific adaptations of the classical protocols for extraction as well as for quantification of their contents. This chapter reviewed the main analytical methods used for the analysis of microalgae biomass and its main vaporizable compounds: proteins, polysaccharides, lipids, pigments and secondary metabolites