Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma

Background Ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-directed CAR T-cell therapy, is effective in heavily pretreated patients with relapsed or refractory multiple myeloma. We investigated cilta-cel in earlier treatment lines in patients with lenalidomide-refractory disease. Methods In this phase 3, randomized, open-label trial, we assigned patients with lenalidomide-refractory multiple myeloma to receive cilta-cel or the physician's choice of effective standard care. All the patients had received one to three previous lines of treatment. The primary outcome was progression-free survival. Results A total of 419 patients underwent randomization (208 to receive cilta-cel and 211 to receive standard care). At a median follow-up of 15.9 months (range, 0.1 to 27.3), the median progression-free survival was not reached in the cilta-cel group and was 11.8 months in the standard-care group (hazard ratio, 0.26; 95% confidence interval [CI], 0.18 to 0.38; P<0.001). Progression-free survival at 12 months was 75.9% (95% CI, 69.4 to 81.1) in the cilta-cel group and 48.6% (95% CI, 41.5 to 55.3) in the standard-care group. More patients in the cilta-cel group than in the standard-care group had an overall response (84.6% vs. 67.3%), a complete response or better (73.1% vs. 21.8%), and an absence of minimal residual disease (60.6% vs. 15.6%). Death from any cause was reported in 39 patients and 46 patients, respectively (hazard ratio, 0.78; 95% CI, 0.5 to 1.2). Most patients reported grade 3 or 4 adverse events during treatment. Among the 176 patients who received cilta-cel in the as-treated population, 134 (76.1%) had cytokine release syndrome (grade 3 or 4, 1.1%; no grade 5), 8 (4.5%) had immune effector cell-associated neurotoxicity syndrome (all grade 1 or 2), 1 had movement and neurocognitive symptoms (grade 1), 16 (9.1%) had cranial nerve palsy (grade 2, 8.0%; grade 3, 1.1%), and 5 (2.8%) had CAR-T-related peripheral neuropathy (grade 1 or 2, 2.3%; grade 3, 0.6%). Conclusions A single cilta-cel infusion resulted in a lower risk of disease progression or death than standard care in lenalidomide-refractory patients with multiple myeloma who had received one to three previous therapies. (Funded by Janssen and Legend Biotech; CARTITUDE-4 ClinicalTrials.gov number, NCT04181827.

Negatively-stained polysomes on rough microsome vesicles viewed by electron microscopy: further evidence regarding the orientation of attached ribosomes

Rough microsomes, derived from rough endoplasmic reticulum of rat liver, were studied by electron microscopy after negative staining, to seek further information about the orientation of ribosomal small and large subunits in bound polysomes. Rough microsomal vesicles were fixed with 2% formaldehyde, centrifuged onto electron-microscopic grid membranes, and were then negatively-stained with 2% phosphotungstic acid. In these preparations, viewed with the electron microscope, flattened rough microsomal vesicles with bound polysomes were sometimes discernible, and the individual ribosomes in the polysomes occasionally showed small and large subunits. The small subunits were uniformly oriented toward the inside of the polysomal curve. The large and small subunits appeared to be alongside one another on the membrane, consistent with the orientation that has been described by Unwin and his co-workers. The boundary between the small and large subunits occurred at approximately the same level in the ribosome where inter-ribosomal strands have been described previously in surface views of bound polysomes in positively-stained electron-microscopic tissue sections. This further confirms the identity of the strands as messenger RNA.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47690/1/441_2004_Article_BF00343942.pd

Uptake and some physiological effects of mercury on water hyacinth, Eichhornia crassipes (Mart) Solms.

The uptake and growth effects of mercury (Hg) on Eichhornia crassipes under field conditions and with lakewater as cultural medium were investigated. Absorption of the heavy metal increase with higher levels of Hg in the culture solution. Roots of the heavy metal than the leaves. The addition of 1 and 2 ppm of Hg into the culture medium was not toxic but significantly reduce fresh matter production, root elongation, ramet formation and total chlorophyll content of mature leaf blades during a four-week culture period. The results strongly suggest a beneficial role of the plant, long considered as a noxious weed, as a bioaccumulator of Hg in polluted lakes

Measuring trainee comprehension of casework relationship in a public welfare orientation program

This study was undertaken as a first step in measuring effectiveness of the Oregon State Public Welfare Orientation Center program in teaching principles of the casework relationship as conceptualized by Felix P. Biestek. This anticipated the development of a reasonably reliable instrument, improvement and validation of which would be undertaken in a subsequent study. The population tested was made up of male and female college graduates, newly hired by the State, who were then entering a four week orientation program for caseworkers. Their education and experience varied, but all had passed the State Civil Service examination for this position. Learning was tested on concepts of purposeful expression of feelings, controlled emotional involvement, acceptance, individualization, .non-judgmental attitude, client self-determination, and confidentiality. From constructed test questions, two tests were formulated and administered in a pretest. Following evaluation of the pretest, the questions were revised and used for two versions of the test which were administered to two orientation classes before and after training. Internal and inter-test reliability, item analysis, and sensitivity were determined for the instrument. Pre-training and post-training differences within and between groups were estimated statistically. Statistical analysis of the data indicated that the tests were moderately reliable both internally and with each other. The testing instruments were able to discriminate between before and after scores. There was significant learning in that scores were higher after completion of the training session beyond chance