ALBERT

Beschreibung: Background: The trombopoietin receptor agonists (TRAs) romiplostim and eltrombopag are effective and safe in the treatment of chronic immune thrombocytopenia (ITP). However, when no response is achieved or when adverse events occur with one TRA the value of the sequential use of romiplostim and eltrombopag has not been clearly established. Here we have evaluated the efficacy and tolerance of using eltrombopag after romiplostim in ITP. Methods: Fifty-one primary ITP patients (aged 18 years or more) who had been sequentially treated first with romiplostim and then with eltrombopag in the Spanish Eltrombopag Registry were retrospectively evaluated. In accordance with the usual standards, complete response was defined as a platelet count of 100x109/L and a response as a platelet count of 30x109/L or a count of at least twice the initial (pre-treatment) value. This study was performed in accordance with the standards of the Helsinki declaration and approved by the Hospital Universitario de Burgos Ethics Committee. Results: The median age of our cohort was 49 [range, 18–83] years. There were 32 women and 19 men. According to the standard definition, patients were allocated to newly diagnosed (n=2), persistent (n=5) and chronic (n=44) ITP groups. The median number of therapies prior to administration of eltrombopag was 4 [range, 2–9], including splenectomy (39%), rituximab (33%) and romiplostim (100%). The median duration of romiplostim use before switching to eltrombopag was 12 (IQR 5–21) months. The reasons for switching from the romiplostim to eltrombopag were: lack of efficacy of romiplostim (n=25), patient's preference (n=16), platelet-count fluctuation (n=6), and side-effects (n=4). The initial response rate to eltrombopag was 41/51 (80.5%), including 67% (n=34) of cases with complete remission. After a median follow-up of 13 months with eltrombopag, 39 patients maintained their response. When eltrombopag was used for patients who were refractory to the maximum romiplostim dose the initial response rate of eltrombopag was 25%. However, 83% of patients who relapsed after their initial response to romiplostim responded to eltrombopag. Sixteen romiplostim responders requested their physicians to switch them to eltrombopag because they preferred an oral drug. The efficacy was maintained after switching in all 16 patients. In the platelet-count fluctuation group, the initial response rate was also 100%. All 4 patients who were switched to eltrombopag because they experienced side-effects of romiplostim achieved complete remission with eltrombopag and their adverse events were resolved. 16 / 51 (33%) patients experienced one or more adverse event during treatment with eltrombopag. The frequency of grade 3–4 adverse events during treatment with eltrombopag was 9.8%. Conclusion: The use of eltrombopag after romiplostim for treating ITP is effective and safe. The reason for discontinuing romiplostim was associated with the response to eltrombopag. Disclosures No relevant conflicts of interest to declare.

Beschreibung: Background: Eltrombopag is effective and safe for treating chronic immune thrombocytopenia (ITP) patients who have not responded to previous therapy. Interestingly, some patients in whom hemostatic platelet counts are achieved with eltrombopag may sustain the platelet response when eltrombopag ceases to be administered. However, the frequency of sustained responses after discontinuing eltrombopag without additional therapy for ITP is largely unknown. Methods: A total of 260 adult patients (aged 18 years or more) with primary ITP treated with eltrombopag included in the Spanish Eltrombopag Registry were retrospectively evaluated. The study was performed in accordance with the standards of the Helsinki declaration and approved by the Hospital Universitario de Burgos Ethics Committee. Results: The median age was 62 [range, 18–93] years. There were 165 women and 95 men. According to the standard definition, patients were allocated to newly diagnosed (n=29), persistent (n=36) and chronic (n=195) ITP groups. The median time from diagnosis to eltrombopag initiation was 24 [range, 1–480] months. The median number of previous therapies was 3 [range, 0–10], including splenectomy (22%), rituximab (23%) and romiplostim (19%). The initial response rate to eltrombopag was 231/260 (89%), including 77% (n=201) cases of complete remission (platelet count ≥100 x 109/L). The median duration of eltrombopag treatment was 6 [range, 1–54] months. Eltrombopag was discontinued in 80 out of 201 (39.8%) patients who achieved CR. Reasons for eltrombopag discontinuation were: persistent response despite a reduction in dose over time (n=33), platelet count 〉400x109/L (n=29), patient’s request (n=5), aspartate aminotransferase elevation (n=3), diarrhea (n=3), thrombosis (n=3) and other reasons (n=4). For analysis of discontinuation, patients with follow-up 〈 6 months (n=15), newly diagnosed ITP (n=11) or patients who received concomitant or previous (6 months before) treatments at the start of eltrombopag use (n=5) were excluded. Of the 49 evaluable patients, 22 (45%) had an immediate relapse after stopping eltrombopag. One patient with sustained response after stopping treatment relapsed at 10 months. A total of 26 patients (53%) showed sustained response after discontinuing eltrombopag without additional ITP therapy, with a median follow-up of 9 [range, 6–25] months. These patients were characterized by a median time since ITP diagnosis of 46.5±114.1 months, with 4/26 having ITP

Beschreibung: Introduction: Carfilzomib dosed at 56 mg/m2 twice a week in combination with dexamethasone (Kd) is a standard of care for RRMM after 1-3 prior lines (PL) based on the ENDEAVOR study. Later, the ARROW study showed Kd dosed at 70 mg/m2 weekly to be superior to Kd dosed at 27 mg/m2 twice a week on RRMM patients (pts) after 2-3 PL. On the other side, Cyclophosphamide is an alkylating agent that has been widely combined with proteasome inhibitors and immunomodulatory drugs in MM, improving their efficacy with a good safety profile. In this phase 2 randomized study, we have compared Kd plus cyclophosphamide (KCyd) with Kd in RRMM after 1-3PL, both with K dosed weekly at 70 mg/m2. Patients and methods: RRMM after 1-3 PL of therapy were included in the trial. Consistently with the ENDEAVOR population, previous therapy with proteasome inhibitors was allowed but refractory patients were excluded. Pts were randomized 1:1 to receive K at a dose of 70 mg/m2 iv on days 1, 8 and 15 plus dexamethasone at a dose of 20 mg PO the day on and the day after K plus/minus KCyd at a dose of 300 mg/m2 IV on days 1, 8 and 15 of each 28 days-cycle, as continuous treatment until progressive disease or unacceptable toxicity. The primary endpoint was PFS and key secondary endpoints included response rates, safety profile, and OS. Results: Between January 2018 and February 2020, 198 RRMM pts were included. 97 pts were randomized to KCyd and 101 to Kd. The baseline characteristics of the patients were well balanced between both groups. The median age was 70 years, and 70% and 28% of pts were older than 65 and 75. The median number of PL was one; 61% of pts had received 1 prior line. 94% and 92% of patients had been exposed to bortezomib in the KCyd and Kd and all of them were sensitive. 72% and 67% of patients had been exposed to IMiD's and 51% and 55% of them were IMiD's-refractory in the KCyd and Kd. Only 4 and 6 patients in KCyd and Kd, had received anti-CD38 antibodies being all refractory. After a median f/u of 15.6 months, median PFS was 20.7 m and 15.2 m in KCyd and Kd (p=0.2). In pts after 1PL, median PFS has not been reached in any arm (p=0.4) and in patients after 2-3PL, KCyd resulted in a median PFS of 20.7 vs 11m for Kd (p=0.4). Of note, in the IMiD-refractory population, the addition of Cy to Kd resulted in a significant benefit in terms of PFS: 26.2 months vs 7.7 months in the Kd arm (p=0.01). OS is immature with 23 and 25 events so far in KCyd and Kd, respectively. The ORR was 78% for KCyd and 73% for Kd: 20% of patients in both arms achieved at least complete response, 33% and 28% very good partial response, respectively, and 25% partial response in both arms. The MRD-ve rate was 4% and 5%. As far as toxicity is concerned, neutropenia was the only hematological adverse event more frequently reported in KCyd compared with Kd, of any grade (24% vs 11%) and grade 3-4 (13% vs 7%). This did not translate into more infections and the rate was comparable in both arms (5% G3-4 in both arms). Thrombocytopenia of any grade and grade 3-4 occurred in 14%/1% and 18%/10% in KCyd/Kd. Cardiovascular events of any grade occurred in 22% and 30% of patients in KCyd and Kd. Nine pts in KCyd developed G3-4 cardiovascular events, these included atrial fibrillation (1pt), cardiac failure (2 pts), myocardial infarct (2 pts), and hypertension (4 pts). In the Kd arm, 11 patients developed G3-4 cardiovascular events and consisted of hypertension in most of them (9 pts). Conclusion: Cyclophosphamide added to Kd 70 mg/m2 weekly in RRMM pts after 1-3 PL prolonged the PFS as compared to Kd particularly in the lenalidomide-refractory population. The administration of K at a dose of 70 mg/m2 weekly was safe and more convenient and overall, the toxicity profile was manageable in both arms. Disclosures Mateos: Abbvie/Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Consultancy, Honoraria; PharmaMar-Zeltia: Consultancy; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Ocio:Janssen: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria; Asofarma: Honoraria; Sanofi: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Honoraria; GSK: Consultancy; MDS: Honoraria; Secura-Bio: Consultancy; Oncopeptides: Consultancy. Sureda Balari:Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Roche: Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria; Merck Sharpe and Dohme: Consultancy, Honoraria, Speakers Bureau; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; BMS: Speakers Bureau; Incyte: Consultancy; Celgene: Consultancy, Honoraria; Gilead/Kite: Consultancy, Honoraria. Oriol:Celgene/Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees. Rosinol Dachs:Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Sanofi: Honoraria. Blade Creixenti:Takeda: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. San-Miguel:Amgen, BMS, Celgene, Janssen, MSD, Novartis, Takeda, Sanofi, Roche, Abbvie, GlaxoSmithKline and Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Beschreibung: Seasonal patterns in hydrography, partial pressure of CO2, fCO2, pHt, total alkalinity, AT, total dissolved inorganic carbon, CT, nutrients, and chlorophyll a were measured in surface waters on monthly cruises at the European Station for Time Series in the Ocean at the Canary Islands (ESTOC) located in the northeast Atlantic subtropical gyre. With over 5 years of oceanographic data starting in 1996, seasonal and interannual trends of CO2 species and air-sea exchange of CO2 were determined. Net CO2 fluxes show this area acts as a minor source of CO2, with an average outgassing value of 179 mmol CO2/m**2 yr controlled by the dominant trade winds blowing from May to August. The effect of short-term wind variability on the CO2 flux has been addressed by increasing air-sea fluxes by 63% for 6-hourly sampling frequency. The processes governing the monthly variations of CT have been determined. From March to October, when CT decreases, mixing at the base of the mixed layer (11.5 ± 1.5 mmol/m**3) is compensated by air-sea exchange, and a net organic production of 25.5 ± 5.7 mmol/m**3 is estimated. On an annual scale, biological drawdown accounts for the decrease in inorganic carbon from March to October, while mixing processes control the CT increase from October to the end of autumn. After removing seasonality variability, fCO2sw increases at a rate of 0.71 ± 5.1 µatm/yr, and as a response to the atmospheric trend, inorganic carbon increases at a rate of 0.39 ± 1.6 µmol/kg yr.

Beschreibung: This data set integrates findings of 16 years (2005 to 2020) of collaborative monitoring efforts across multiple institutions in the Gulf of California.The data encompasses information of 13 species of marine herbivorous fishes belonging to five families: Acanthuridae, Girellidae, Kyphosidae, Pomacentridae and Scaridae. This database presents 884 records of biomass from 15,542 visual censuses assessed by scuba diving in 34 localities (comprising 268 rocky and coral reefs sites). Visual censuses consisted of belt transects (250 m2, 100 m2, and 60 m2) laid parallel to the coastline preserving a similar depth profiles. Along these transects, trained underwater monitors, identified the species, recorded the abundance of all the adult individuals of the 13 targeted species and visually estimated the total length (cm) of each fish. The information for each transect in the database, is presented as the biomass (grams per square meter), which was estimated based on the size per individual as well as the weight-length relationship for each species, available on the literature. In the database is also integrated the information of the latitude and longitude of each locality, type of management, localities in the Gulf of California, institutions, the initial and final year of data, total number of years, as well as the mean, standard deviation, sample size, slope (annual rate of change), probability value, standard error and minimum and maximum value calculated for each species within each locality. This dataset represents a historical reference point for the condition of the 13 species found in the Gulf of California. It can be used to perform evaluations of how herbivorous fish communities have changed over time and across different locations. This is particularly relevant due to the influence of global changes leading to tropicalization in the study area. Furthermore, this information holds significance as it supplies essential insights to those responsible for the management of protected zones in the Gulf and the broader eastern tropical Pacific region. communities have changed over time and across different locations. This is particularly relevant due to the influence of global changes leading to tropicalization in the study area. Furthermore, this information holds significance as it supplies essential insights to those responsible for the management of protected zones in the Gulf and the broader eastern tropical Pacific region.

Beschreibung: Through collaborative monitoring involving multiple academic, government, and civil institutions over a span of 16 years (2005 to 2020), we compiled 884 records of the density of 13 species of marine herbivorous fishes. The data was collected through 15,542 visual censuses conducted by scuba diving in 34 localities, encompassing 268 rocky and coral reef sites. These censuses utilized belt transects (250 m², 100 m², and 60 m²) parallel to the coastline at similar depth profiles. Trained underwater monitors recorded abundances of all adult individuals of the 13 targeted species along the transects. The information for each transect in the database is presented as the average fish density (individuals per square meter), estimated based on the abundance for each species. The database integrates information on latitude, longitude, type of management, localities in the Gulf of California, institutions, initial and final years of data collection, total number of years, as well as mean, standard deviation, sample size, slope (annual rate of change), probability value, standard error, and minimum and maximum values calculated for each species within each locality. This dataset serves as a historical benchmark for assessing the status of 13 species in the Gulf of California. It enables the examination of changes in herbivorous fish communities over time and across various locations, which is crucial given the impact of global changes leading to tropicalization in the study area. The data is particularly important for providing valuable insights to those managing protected areas in the Gulf and the broader eastern tropical Pacific region.

Beschreibung: This dataset lists metadata of georeferenced stations obtained from 31 published studies of benthic foraminifera from surface sediments of the Eastern Pacific between 1929 and 2019 .The publications included in the dataset do not contain tabulated quantitative species abundance data of benthic foraminifera assemblages. Explanations about column names and column codes can be found in the companion file.

Beschreibung: The BENFEP_v2 database represents an upgraded version of the "BENthic Foraminifera quantitative database from surface sediments of the Eastern Pacific" (BENFEP_v1,https://doi.org/10.1594/PANGAEA.947086). In this new version we have added five new quantitative datasets and amended the geolocations of a few samples. The taxonomy of benthic foraminiferal species has been updated to World Foraminifera Database (Hayward et al., 2023, last access: 31 July 2023). BENFEP_v2 is presented in a long format. Column codes and column names can be found in the related manuscript (Diz et al.,2023).

Beschreibung: The BENFEP_v1 database contains georeferenced quantitative data of benthic foraminifera species from the Eastern Pacific surface sediments collated from 50 published and unpublished datasets. We consider one data as quantitative when the species abundance in an assemblage is provided as number of individuals (counts), relative abundance (percent) or density (number of individuals per volume unit). The taxonomy of benthic foraminiferal species is harmonized using the World Foraminifera Database (Hayward et al., 2022, last accessed on 22-12-08). Census data are provided in their original form and including with coded metadata (e.g., sampling devices, interval, type of assemblage, size fraction) to facilitate data analysis using different software. BENFEP_v1 is presented in short and in long format. In BENFEP_v1_short, foraminiferal entities (valid species or species identified to genus level) are provided as columns whereas in BENFEP_v1_long, foraminiferal entities are indicated in a single column. The long format integrates the taxonomic information extracted from WoRMS as well as the original authors' species designations which are provided in the related manuscript (Diz et al., doi:10.5194/essd-2022-324). Explanations about column names and column codes for BENFEP_v1_short and BENFEP_v1_long can be found in the companion files.