Identification of neutralising pembrolizumab anti-drug antibodies in patients with melanoma.

Development of anti-drug antibodies (ADAs) can interfere with therapeutic monoclonal antibodies and may lead to drug neutralisation and clinical disease progression. Measurement of circulating drug levels and development of ADAs in the setting of anti-programmed cell death-1 agent pembrolizumab has not been well-studied. Enzyme-linked immunosorbent assays were used to measure pembrolizumab drug level and ADAs in 41 patients with melanoma at baseline, Time-point 1 (3 weeks) and Time-point 2 (21 weeks). Assay results were related to patient demographics and clinical outcome data at 6 months. The median pembrolizumab drug level at 3 weeks was 237 ng/µL and did not correlate with age, sex or body surface area.17/41 patients had an ADA detected at any timepoint, with the highest prevalence at Timepoint 1 (median concentration = 17 ng/µL). The presence of an ADA did not correlate with clinical progression at 6 months. 3/41 (7%) of patients displayed a falling pembrolizumab drug level and rising ADA titre between Timepoint 1 and 2 suggestive of a neutralising ADA. Pembrolizumab drug levels and ADAs can be readily measured. The rates of total and treatment-emergent ADAs may be higher in "real-word" settings than those previously reported. Larger studies are needed to determine effect of neutralising ADAs on long-term clinical outcome.

Clinical heterogeneity in 80 home-reared children with cri du chat syndrome.

A population of 80 home-reared children with cri du chat syndrome was investigated to document the clinical heterogeneity of the syndrome and to analyze the factors influencing the severity of the phenotypic characteristics. When individuals with isolated deletions were compared with those possessing unbalanced translocations involving other chromosomes in addition to number 5, the latter group had a greater incidence of physical anomalies, more frequent hospitalizations, and a higher mortality. Chronic complaints in both groups included upper respiratory tract infection, otitis media, and a previously unrecognized association with gastrointestinal tract anomalies. In children with terminal deletions, there was a significant negative correlation between the size of the deletion and the individual's intelligence quotient. In addition, patients with larger deletions had more severe growth retardation, particularly with respect to the degree of microcephaly. The gradual progression with age of the characteristic facial features remained consistent regardless of differing racial backgrounds and the size of the deletion. Our findings delineate the variation in the clinical and karyotypic features of this syndrome.

Psychomotor development in 65 home-reared children with cri-du-chat syndrome.

The psychomotor development of 65 noninstitutionalized individuals with cri-du-chat syndrome was examined through parental questionnaire responses and supporting medical records. Social quotients determined by a Vineland Maturity Scale ranged from 6 to 85, the ages at which developmental milestones were attained varied from the upper limits of normal to six years delayed. Achievement levels were influenced favorably by the early introduction of special education, and were affected adversely by the presence of an unbalanced translocation. This study suggests that many children with cri-du-chat syndrome can attain developmental and social skills normally seen in 5- to 6-year-old children, although their linguistic abilities are seldom as advanced. Contrary to the commonly portrayed clinical picture of severe mental retardation and bedridden debilitation, the older home-reared cri-du-chat child was usually ambulatory, had a moderate degree of independence in self-care skills, and was able to communicate either verbally or through gestural sign language. Physicians and parents should be aware of the full range of psychomotor potential of the child with cri-du-chat syndrome in order to make informed decisions concerning institutional placement.