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Daratumumab is a CD38 monoclonal antibody recently approved for the treatment of multiple myeloma (MM). We report daratumumab pharmacokinetic data from GEN501, a phase I/II dose-escalation (0.005–24 mg/kg) and dose-expansion (8 or 16 mg/kg) study, and SIRIUS, a phase II study (8 or 16 mg/kg), in relapsed or refractory MM. Noncompartmental analysis was conducted to characterize daratumumab pharmacokinetics, and, in both studies, daratumumab exhibited nonlinear pharmacokinetic characteristics. Decreasing daratumumab clearance with increasing dose suggests saturation of target-mediated clearance at higher dose levels, whereas decreasing clearance over time with repeated dosing may be due to tumor burden reductions as CD38-positive cells are eliminated. These and other pharmacokinetic data analyses support the use of the recommended dose regimen of daratumumab (16 mg/kg weekly for 8 weeks, every 2 weeks for 16 weeks, and every 4 weeks thereafter) to rapidly saturate target-mediated clearance during weekly dosing and maintain saturation when dosing every 2 or 4 weeks.

Objective The aim of this study was to understand the influence of disease and patient characteristics on exposure to daratumumab, an immunoglobulin Gκ (IgGκ) monoclonal antibody, and clinical outcomes in relapsed or refractory multiple myeloma (MM). Patients and Methods Baseline myeloma type, albumin levels, renal/hepatic function, age, sex, race, weight, Eastern Cooperative Oncology Group (ECOG) status, refractory status, and number of prior therapies were evaluated using data from two clinical studies—GEN501 ( N  = 104) and SIRIUS ( N  = 124). Results Daratumumab clearance was approximately 110% higher in IgG myeloma patients than non-IgG myeloma patients, leading to significantly lower exposure in IgG myeloma patients based on maximum trough serum concentrations ( p  < 0.0001). However, the overall response rate was similar for IgG and non-IgG myeloma patients (odds ratio 1.08, 95% confidence interval 0.54–2.17, p  = 0.82). For a given exposure, the drug effect was significantly higher (approximately two times) in IgG versus non-IgG patients ( p  = 0.03). The influence of other patient and disease characteristics on daratumumab exposure was minimal and no significant effect on efficacy was observed ( p  ≥ 0.1). The incidences of infections and overall grade 3 or higher adverse events in subpopulations were generally consistent with that of the overall population. Conclusion Due to competition with the MM-produced IgG M-protein for neonatal Fc receptor protection from clearance, IgG-based monoclonal antibodies in general may have significantly higher clearance and lower concentrations in IgG MM patients compared with non-IgG MM patients. Careful evaluation of the impact of exposure and patient and disease characteristics on safety and efficacy is warranted for all IgG-based monoclonal antibodies used in MM.

The toxicities of four classes of insecticides, emamectin benzoate (avermectin), chlorfenapyr (pyrrole), fipronil (phenylpyrazole), and tebufenozide (benzoylhydrazide) were compared using an artificial diet assay and a residual efficacy assay against several species of Lepidoptera. Emamectin benzoate was consistently the most toxic insecticide; it was 20- to 64,240-times more toxic than the other compounds tested. The LC90 values for emamectin benzoate ranged from 0.0050 to 0.0218 ug/ml for six species of Lepidoptera. Similarly, chlorfenapyr displayed consistent toxicity to all species, with LC90 values ranging from 1.9 to 4.6 ug/ml. The toxicities of fipronil and tebufenozide varied among the species tested. Fipronil LC90 values varied 501-fold (range, 0.64 to 321.3 ug/ml), while tebufenozide toxicity varied 113-fold (range, 0.24 to 27.1 ug/ml) among species tested. In residual efficacy tests conducted in the glasshouse, all compounds were effective (i.e., >90% mortality) at controlling Heliothis virescens on garbanzo bean at projected field rates and at 1/10 of projected field rates with fipronil and emamectin benzoate. Emamectin benzoate, chlorfenapyr and tebufenozide were effective at controlling Spodoptera exigua on sugar beet at projected field rates. However, mortality with fipronil was reduced to 20% or less at 7 to 14 days after treatment. All compounds at projected field use rates were effective against Trichoplusia ni on cabbage, although tebufenozide was the only compound effective at 1/10 of projected field rate for 14 days after treatment. However, tebufenozide was ineffective against Plutella xylostella at projected field use rates on cabbage while emamectin benzoate, chlorfenapyr, and fipronil were effective. The potential of these compounds for arthropod pest management are discussed.

Experiments were conducted during two consecutive growing seasons to evaluate food baits for pre-plant sampling of wireworms that attack potato in southern Florida. Wireworm species studied were: Melanotus communis (Gyllenhal), southern potato wireworm, Conoderus falli Lane, C. amplicollis (Gyllenhal), and C. rudis (Brown). Baits evaluated were hybrid sweet corn seed, hybrid sorghum-sudangrass seed, a 1:1 mixture of corn and sorghum-sudangrass seed, a whole sweet corn ear, potato seed pieces, a 1:1 mixture of oatmeal and corn flake, rolled oats, and carrots. In the first year, numbers of wireworm larvae did not differ between food bait and soil samples for most food baits tested. Melanotus communis larvae were most numerous in the oatmeal-corn flake and sorghum-sudangrass seed baits. Conoderus spp. larvae were most numerous in the sorghum-sudangrass seed and corn ear baits. In the second year, M. communis larvae were more numerous in food baits than in soil samples, and more numerous in the oatmeal-corn flake and rolled oat baits than in other food baits. Numbers of Conoderus spp. larvae did not differ between food bait and soil samples nor among food baits. In addition to attracting more wireworms, oatmeal-corn flake and rolled oat baits had some of the shorter processing times. The use of one of these two baits is currently recommended for pre-plant sampling of wireworms in potato fields in southern Florida. /// Se hicieron experimentos antes de la siembra durante dos temporadas de crecimiento consecutivos para evaluar cebos como muestreo de gusanos de alambre que atacan la papa en el sur de la Florida. Las especies estudiadas fueron: Melanotus communis (Gyllenhal), Conoderus falli Lane, C. amplicollis (Gyllenhal, y C. rudis (Brown). Los cebos evaluados fueron semilla de un híbrido de maíz dulce, semilla de un híbrido de sorgo-hierba de sudán, una mezcla 1:1 de semilla de maíz y sorgo-hierba de sudán, una mazorca completa de maíz dulce, pedazos de semillas de papa, una mezcla de 1:1 de harina de avena y copos de maíz, avena \"enrollada\", y zanahorias. En el primer año, no hubo diferencia en el número de gusanos de alambres entre los cebos y las muestras de tierra en la mayoría de las cebos probados. Larvas de Melanotus communis fueron más numerosas en los cebos de harina de avena-copos de maíz y en semillas de sorgo-hierba de sudán. Larvas de Conoderus spp. fueron más numerosas en semillas de sorgo-hierba de sudán y en mazorcas completas de maíz. En el segundo año, larvas de M. communis fueron más numerosas en cebos que en muestras de suelo, y más numerosas en la harina de avena-copos de maíz y en avena \"enrollada\" que en otros cebos. No hubo diferencia en el número de larvas de Conoderus spp. entre los cebos y las muestras de tierra, ni entre los cebos. Aparte de que atrayeron más gusanos de alambre, cebos de harina de avena-copos de maíz y de avena \"enrollada\" tuvieron uno de los tiempos más cortos de procesamiento. Se recomienda el uso de uno de estos dos cebos para el muestreo de gusanos de alambre antes de la siembra de papas en el sur de la Florida.

Six solid formulations of emamectin benzoate (one wettable powder (WP) blend, one wettable dispersible granule (WG), and four soluble granules (SG)) were compared with an emulsifiable concentrate (EC) formulation for their residual effectiveness at controlling tobacco budworm, Heliothis virescens (F.), beet armyworm, Spodoptera exigua (Hübner), and cabbage looper, Trichoplusia ni (Hübner), in three glasshouse tests. Emamectin benzoate was applied to plants at two rates in each trial (8.4 and 0.084 g ai/ha). Results from the glasshouse studies showed that most formulations were comparable at controlling all lepidopterous pests tested. Four field trials conducted in Florida confirmed that all formulations were comparable in their effectiveness at controlling populations of lepidopterous pests on vegetables, including diamondback moth, Plutella xylostella (L.), on cabbage, southern armyworm, Spodoptera eridania (Cramer), on pepper, and T. ni and S. exigua on celery. These studies identified a novel SG formulation of emamectin benzoate that was comparable to the EC formulation in its effectiveness at controlling lepidopterous pests, but superior to the EC in terms of safety to man and the environment. This novel SG formulation is currently being developed for control of lepidopterous pests on a variety of crops. /// El efecto residual de seis formulaciones sólidas de benzoato de emamectina (una mezcla de polvo humedecible, gránulos humedecibles dispersables, y cuatro gránulos solubles) fue comparado con el de un concentrado emulsificable en el control de Heliothis virescens (F.), Spodoptera exigua (Hübner) y Trichoplusia ni (Hübner) en tres pruebas, en tres invernaderos. El benzoato de emamectina fue aplicado a las plantas a dos concentraciones en cada prueba (8.4 y 0.084 g ia/ha). Los resultados de los estudios de invernadero mostraron que la mayoría de las formulaciones fueron comparables con en el control de todos los lepidópteros probados. Cuatro pruebas de campo conducidas en la Florida confirmaron que todas las formulaciones fueron comparables en su efectividad al controlar poblaciones de lepidópteros plagas de vegetales, incluyendo Plutella xylostella (L.), en col, Spodoptera eridania (Cramer) en pimiento, y T. ni y S. exigua en apio. Los estudios identificaron una nueva fórmula de gránulos solubles de benzoato de emamectina que fue comparable con el concentrado emulsionable en cuanto a su efectividad al controlar lepidópteros plagas pero es superior al concentrado emusionable en términos de seguridad al hombre y el ambiente. Esta nueva formulación de gránulos soluble es actualmente desarrollada para el control de lepidópteros plagas de varios cultivos.

The infectivity, incubation time, and reproduction of three heterorhabditid nematodes, Heterorhabditis sp. Bacardis and FL2122 strains and H. bacteriophora Poinar HP88 strain were studied in two insect hosts, an apionid weevil, Cylas formicarius (F.), and a pyralid moth, Galleria mellonella (L.). Two of the nematodes, Heterorhabditis sp. Bacardis and FL2122 strains, were of tropical or subtropical origin, whereas the third nematode, H. bacteriophora HP88 strain, was of temperate origin. Infectivity did not differ among nematodes within each host; however, it did differ between hosts for the Bacardis strain. Cylas formicarius was more susceptible to this nematode than G. mellonella. Incubation times also did not differ among nematodes within hosts; however, incubation times were 3.2-4.3 d shorter in C. formicarius than in G. mellonella. Progeny production differed (although not significantly consistent) among nematodes and was highest for Heterorhabditis sp. Bacardis followed by the Heterorhabditis sp. FL2122 and H. bacteriophora HP88 in both hosts. Percentages of infected cadavers that produced progeny were consistently higher for the tropical and subtropical nematodes, Heterorhabditis sp. Bacardis and FL2122, than for the temperate nematode, H. bacteriophora HP88, in both hosts. Patterns of emergence from cadavers were consistent in G. mellonella; most progeny emerged by 23 d after inoculation and emergence lasted for up to 48 d after inoculation. Conversely, emergence patterns varied markedly in C. formicarius. Emergence lasted for up to 29 d after inoculation and peak emergence varied between 12 and 28 d after inoculation. Progeny production in C. formicarius was not related to the biomass of the host cadaver. /// Fueron estudiadas la infectividad, el tiempo de incubación y la reproducción de tres nemátodos heterorhabdítidos, las cepas Bacardis y FL2122 de Heterorhabditis sp., y la cepa HP88 de H. bacteriophora Poinar, en dos insectos hospedantes, un gorgojo apiónido, Cylas formicarius (F.), y una polilla pirálida, Galleria mellonella (L.). Dos de los nemátodos, las cepas Bacardis y FL2122 de Heterorhabditis sp., fueron de origen tropical o subtropical, mientras que el tercer nemátodo, la cepa HP88 de H. bacteriophora Poinar, fue de origen templado. La infectividad no difirió entre los nemátodos dentro de cada hospedante; sin embargo, difirió entre los hospedantes para la cepa Bacardis. Cylas formicarius fue más susceptible a este nemátodo que G. mellonella. Los períodos de incubación tampoco difirieron entre los nemátodos dentro de los hospedantes; sin embargo, los tiempos de incubación fueron 3.2-4.3 días más cortos en C. formicarius que en G. mellonella. La producción de progenie difirió (aunque no con significación consistente) entre los nemátodos y fue más alta para Heterorhabditis sp. Bacardis, seguida por Heterorhabditis sp. FL2122 y por H. bacteriophora HP88 en ambos hospedantes. Los porcentajes de cadáveres infectados que produjeron progenie fueron consistentemente más altos para los nemátodos tropicales y subtropicales, Heterorhabditis sp. Bacardis y Heterorhabditis sp. FL2122, que para el templado, H. bactriophora HP88, en ambos hospedantes. Los patrones de emergencia de los cadáveres fueron consistentes en G. mellonella; la mayoría de la progenie emergió antes de los 23 días posteriores a la inoculación y la emergencia duró al menos 48 días después de la inoculación. Por el contrario, los patrones de emergencia variaron marcadamente entre los 12 y los 28 días después de la inoculación. La producción de progenie en C. formicarius no estuvo relacionada con la biomasa del cadáver del hospedante.

Emamectin benzoate (MK-244; Merck & Co., Rahway, NJ), used alone and alternated with Bacillus thuringiensis (Berliner) ssp. aizawai (Bta), Bta alone, and B. thuringiensis ssp. kurstaki (Btk) alone, were evaluated for control of diamondback moth, Plutella xylostella (L.), in head cabbage at three locations in Florida. Additional treatments unique to each location were also evaluated. Emamectin benzoate alone, Bta alone, emamectin benzoate alternated with Bta, and mevinphos were shown to be effective. Btk was less efficacious than Bta at two locations. /// El benzoato de emamectina (MK-244; Merck & Co., Rahway, NJ) usado solo y alternado con Bacillus thuringiensis (Berliner) ssp. aizawai (Bta), Bta solo, y B. thuringiensis ssp kurstaki (Btk) solo, fueron evaluados para el control de la polilla de diamante, Plutella xylostella (L.), en col de repollo en tres localidaes de la Florida. También fueron evaluados tratamientos adicionales únicos en cada localidad. El benzoato de emamectina solo, Bta solo, el benzoato de emamectina alternado con Bta, y el mevinfós mostraron ser efectivos. Btk fue menos eficaz que Bta en las dos localidades.

Six solid formulations of emamectin benzoate (three impregnated powder blends, two dry powder blends, and one soluble granule) were compared with an emulsifiable concentrate (EC) formulation for their residual efficacy at killing tobacco budworm, Heliothis virescens (F.) (= Helicoverpa virescens (F.)), and beet armyworm, Spodoptera exigua (Hübner), in glasshouse tests. Two trials were conducted. Emamectin benzoate was applied to plants at two rates in each trial (8.4 and 0.084 g ai/ha in the first trial; and 8.4 and 0.84 g ai/ha in the second trial). The first trial was conducted in a glasshouse; in the second trial, plants were treated in the glasshouse and moved outdoors for the duration of the study. In the first trial, all three impregnated powder blends, one dry powder blend, and the EC formulation were comparable in their effectiveness at controlling both targets when applied at the high rate (8.4 g ai/ha). At the low rate, efficacy at controlling H. virescens did not differ among formulations, whereas the two powder formulations provided the longest residual efficacy against S. exigua. In the second trial, one impregnated powder blend, two dry powder blends, a soluble granule, and the EC formulation were comparable in their effectiveness at killing both species up to 10 days after application when applied at the high rate (8.4 g ai/ha). At the low rate (0.84 g ai/ha), one powder formulation was consistently more effective at controlling S. exigua, whereas no formulation consistently outperformed all others at controlling H. virescens. Two field studies demonstrated that two dry powder blend formulations were very effective and comparable to the EC formulation at controlling Helicoverpa zea (Boddie), Keiferia lycopersicella (Walsingham), and S. exigua on tomato. These data demonstrate that solid formulations of emamectin benzoate have potential for control of Lepidoptera. The importance of a solid formulation for emamectin benzoate is discussed. /// La eficacia residual sobre el gusano cogollero del tabaco, Heliothis virescens (F.) (=Helicoverpa virescens (F.)) y el gusano de la remolacha, Spodoptera exigua Hübner, de seis formulaciones sólidas de benzoato de emamectin (tres mezclas de polvos impregnados, dos mezclas de polvo seco y un granulado sólido) fue comparada con la de un concentrado emulsionable (CE) en ensayos de invernadero. Dos ensayos fueron realizados. El benzoato de emamectin fue aplicado a las plantas a dos dosis en cada ensayo (8.4 y 0.084 g ai/ha en el primer ensayo, y 8.4 y 0.84 g ai/ha, en el segundo). El primer ensayo fue llevado a cabo en un invernadero; en el segundo ensayo las plantas fueron tratadas en el invernadero y se mantuvieron fuera durante el resto del estudio. En el primer ensayo, las efectividades de las tres mezclas de polvos impregnados, una mezcla de polvo seco y la EC fueron comparables en su efectividad para controlar a los dos sujetos cuando se aplicaron a alta dosis (8.4 g ai/ha). A la dosis baja, la eficacia para controlar H. virescens no difirió entre las formulaciones, mientras que las dos formulaciones de polvo mostraron la más larga eficacia residual contra S. exigua. En el segundo ensayo, una mezcla de polvo impregnado, dos mezclas de polvos secos, un granulado soluble y la formulación del CE tuvieron efectividades comparables contra ambas especies hasta los 10 días después de la aplicación, cuando se aplicaron a la dosis alta (8.4 g/ai/ha). A la dosis baja (0.84 g ai/ha), una formulación de polvo fue consistentemente más efectiva en el control de S. exigua, y ninguna formulación fue más efectiva que las otras controlando H. virescens. Dos estudios de campo demostraron que dos mezclas de polvo seco fueron muy efectivas y comparables con la formulación de CE en el control de Helicoverpa zea (Boddie), Keiferia lycopersicella (Walshingham) y S. exigua en el tomate. Estos datos demuestran que las formulaciones sólidas de benzoato de emamectin tienen potencial para el control de Lepidoptera. Se discute la importancia de una formulación para el benzoato de emamectin.

Aqueous suspensions of HP88 nematodes were as effective as applications of Galleria mellonella cadavers infected with HP88 for controlling damage by sweetpotato weevil to storage roots. Persistence of nematodes was similar for the two types of application.