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- Usmani, SZ, et al.
(författare)
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Final analysis of the phase III non-inferiority COLUMBA study of subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma
- 2022
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 107:10, s. 2408-2417
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Tidskriftsartikel (refereegranskat)abstract
- In the primary analysis of the phase III COLUMBA study, daratumumab by subcutaneous administration (DARA SC) demonstrated non-inferiority to intravenous administration (DARA IV) for relapsed or refractory multiple myeloma (RRMM). Here, we report the final analysis of efficacy and safety from COLUMBA after a median of 29.3 months follow-up (additional 21.8 months after the primary analysis). In total, 522 patients were randomized (DARA SC, n=263; DARA IV, n=259). With longer follow-up, DARA SC and DARA IV continued to show consistent efficacy and maximum trough daratumumab concentration as compared with the primary analysis. The overall response rate was 43.7% for DARA SC and 39.8% for DARA IV. The maximum mean (standard deviation [SD]) trough concentration (cycle 3, day 1 pre-dose) of serum DARA was 581 (SD, 315) μg/mL for DARA SC and 496 (SD, 231) μg/mL for DARA IV. Median progression-free survival was 5.6 months for DARA SC and 6.1 months for DARA IV; median overall survival was 28.2 months and 25.6 months, respectively. Grade 3/4 treatment-emergent adverse events occurred in 50.8% of patients in the DARA SC group and 52.7% in the DARA IV group; the most common (≥10%) were thrombocytopenia (DARA SC, 14.2%; DARA IV, 13.6%), anemia (13.8%; 15.1%), and neutropenia (13.1%; 7.8%). The safety profile remained consistent with the primary analysis after longer follow-up. In summary, DARA SC and DARA IV continue to demonstrate similar efficacy and safety, with a low rate of infusion-related reactions (12.7% vs. 34.5%, respectively) and shorter administration time (3-5 minutes vs. 3-7 hours) supporting DARA SC as a preferable therapeutic choice. (Clinicaltrials gov. Identifier: NCT03277105.
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- Lim, Artem G., et al.
(författare)
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Carbon emission and export from the Ket River, western Siberia
- 2022
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Ingår i: Biogeosciences. - : Copernicus Publications. - 1726-4170 .- 1726-4189. ; 19:24, s. 5859-5877
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Tidskriftsartikel (refereegranskat)abstract
- Despite recent progress in the understanding of the carbon (C) cycle of Siberian permafrost-affected rivers, spatial and seasonal dynamics of C export and emission from medium-sized rivers (50 000-300 000 km2 watershed area) remain poorly known. Here we studied one of the largest tributaries of the Ob River, the Ket River (watershed Combining double low line 94 000 km2), which drains through pristine taiga forest of the boreal zone in the West Siberian Lowland (WSL). We combined continuous and discrete measurements of carbon dioxide (CO2) concentration using submersible CO2 sensor and floating chamber flux (FCO2), with methane (CH4), dissolved organic and inorganic C (DOC and DIC, respectively), particulate organic C and total bacterial concentrations over an 800 km transect of the Ket River main stem and its 26 tributaries during spring flood (May 2019) and 12 tributaries during summer baseflow (end of August-beginning of September 2019). The partial pressure of CO2 (pCO2) was lower and less variable in the main stem (2000 to 2500 μatm) compared to that in the tributaries (2000 to 5000 μatm). In the tributaries, the pCO2 was 40 % higher during baseflow compared to spring flood, whereas in the main stem, it did not vary significantly across the seasons. The methane concentration in the main stem and tributaries was a factor of 300 to 1900 (flood period) and 100 to 150 times lower than that of CO2 and ranged from 0.05 to 2.0 μmol L-1. The FCO2 ranged from 0.4 to 2.4 g C m-2 d-1 in the main channel and from 0.5 to 5.0 g C m-2 d-1 in the tributaries, being highest during August in the tributaries and weakly dependent on the season in the main channel. During summer baseflow, the DOC aromaticity, bacterial number, and needleleaf forest coverage of the watershed positively affected CO2 concentrations and fluxes. We hypothesize that relatively low spatial and seasonal variability in FCO2 of the Ket River is due to a flat homogeneous landscape (bogs and taiga forest) that results in long water residence times and stable input of allochthonous dissolved organic matter (DOM), which dominate the FCO2. The open water period (May to October) C emission from the fluvial network (main stem and tributaries) of the Ket River was estimated to 127 ± 11 Gg C yr-1, which is lower than the downstream dissolved and particulate C export during the same period. The estimated fluvial C emissions are highly conservative and contain uncertainties linked to ignoring hotspots and hot moments of emissions, notably in the floodplain zone. This stresses the need to improve the temporal resolution of FCO2 and water coverage across seasons and emphasizes the important role of WSL rivers in the release of CO2 into the atmosphere.
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