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Journal of Clinical Oncology : Official... Apr 2023Epcoritamab is a subcutaneously administered CD3xCD20 T-cell-engaging, bispecific antibody that activates T cells, directing them to kill malignant CD20 B cells....
PURPOSE
Epcoritamab is a subcutaneously administered CD3xCD20 T-cell-engaging, bispecific antibody that activates T cells, directing them to kill malignant CD20 B cells. Single-agent epcoritamab previously demonstrated potent antitumor activity in dose escalation across B-cell non-Hodgkin lymphoma subtypes.
PATIENTS AND METHODS
In the dose-expansion cohort of a phase I/II study (ClinicalTrials.gov identifier: NCT03625037), adults with relapsed or refractory CD20 large B-cell lymphoma and at least two prior therapy lines (including anti-CD20 therapies) received subcutaneous epcoritamab in 28-day cycles (once weekly step-up doses in weeks 1-3 of cycle 1, then full doses once weekly through cycle 3, once every 2 weeks in cycles 4-9, and once every 4 weeks in cycle 10 and thereafter) until disease progression or unacceptable toxicity. The primary end point was overall response rate by the independent review committee.
RESULTS
As of January 31, 2022, 157 patients were treated (median age, 64 years [range, 20-83]; median of three [range, 2-11] prior therapy lines; primary refractory disease: 61.1%; prior chimeric antigen receptor (CAR) T-cell exposure: 38.9%). At a median follow-up of 10.7 months, the overall response rate was 63.1% (95% CI, 55.0 to 70.6) and the complete response rate was 38.9% (95% CI, 31.2 to 46.9). The median duration of response was 12.0 months (among complete responders: not reached). Overall and complete response rates were similar across key prespecified subgroups. The most common treatment-emergent adverse events were cytokine release syndrome (49.7%; grade 1 or 2: 47.1%; grade 3: 2.5%), pyrexia (23.6%), and fatigue (22.9%). Immune effector cell-associated neurotoxicity syndrome occurred in 6.4% of patients with one fatal event.
CONCLUSION
Subcutaneous epcoritamab resulted in deep and durable responses and manageable safety in highly refractory patients with large B-cell lymphoma, including those with prior CAR T-cell exposure.
Topics: Adult; Humans; Middle Aged; Neoplasm Recurrence, Local; Lymphoma, Large B-Cell, Diffuse; Antineoplastic Agents; T-Lymphocytes; Receptors, Chimeric Antigen
PubMed: 36548927
DOI: 10.1200/JCO.22.01725 -
Current Opinion in Anaesthesiology Jun 2021Children are at risk of severe hypoxemia in the perioperative period owing to their unique anatomy and physiology. Safe and effective airway management strategies are... (Review)
Review
PURPOSE OF REVIEW
Children are at risk of severe hypoxemia in the perioperative period owing to their unique anatomy and physiology. Safe and effective airway management strategies are therefore key to the practice of pediatric anesthesia. The goal of this review is to highlight recent publications (2019-2021) aimed to advance pediatric airway safety and to highlight a proposed simple, pediatric-specific, universal framework to guide clinical practice.
RECENT FINDINGS
Recent investigations demonstrate that infants with normal and difficult airways experience high incidences of multiple laryngoscopy attempts and resulting hypoxemia. Video laryngoscopy may improve tracheal intubation first attempt success rate in infants with normal airways. In infants with difficult airways, standard blade video laryngoscopy is associated with higher first attempt success rates over non-standard blade video laryngoscopy. Recent studies in children with Pierre Robin sequence and mucopolysaccharidoses help guide airway equipment and technique selection. Department airway leads and hospital difficult airway services are necessary to disseminate knowledge, lead quality improvement initiatives, and promote evidence-based practice guidelines.
SUMMARY
Pediatric airway management morbidity is a common problem in pediatric anesthesia. Improvements in individual practitioner preparation and management strategies as well as systems-based policies are required. A simple, pediatric-specific, universal airway management framework can be adopted for safe pediatric anesthesia practice.
Topics: Airway Management; Child; Humans; Hypoxia; Infant; Intubation, Intratracheal; Laryngoscopes; Laryngoscopy
PubMed: 33935175
DOI: 10.1097/ACO.0000000000000993 -
Cell Stem Cell Nov 2020Non-coding mutations at the far end of a large gene desert surrounding the SOX9 gene result in a human craniofacial disorder called Pierre Robin sequence (PRS)....
Non-coding mutations at the far end of a large gene desert surrounding the SOX9 gene result in a human craniofacial disorder called Pierre Robin sequence (PRS). Leveraging a human stem cell differentiation model, we identify two clusters of enhancers within the PRS-associated region that regulate SOX9 expression during a restricted window of facial progenitor development at distances up to 1.45 Mb. Enhancers within the 1.45 Mb cluster exhibit highly synergistic activity that is dependent on the Coordinator motif. Using mouse models, we demonstrate that PRS phenotypic specificity arises from the convergence of two mechanisms: confinement of Sox9 dosage perturbation to developing facial structures through context-specific enhancer activity and heightened sensitivity of the lower jaw to Sox9 expression reduction. Overall, we characterize the longest-range human enhancers involved in congenital malformations, directly demonstrate that PRS is an enhanceropathy, and illustrate how small changes in gene expression can lead to morphological variation.
Topics: Cell Differentiation; Humans; Mutation; Neural Crest; Pierre Robin Syndrome; Regulatory Sequences, Nucleic Acid; SOX9 Transcription Factor
PubMed: 32991838
DOI: 10.1016/j.stem.2020.09.001 -
Atlas of the Oral and Maxillofacial... Mar 2022
Review
Topics: Airway Obstruction; Humans; Infant; Infant, Newborn; Mandible; Osteogenesis, Distraction; Pierre Robin Syndrome; Treatment Outcome
PubMed: 35256110
DOI: 10.1016/j.cxom.2021.11.001 -
Seminars in Fetal & Neonatal Medicine Dec 2021The field of craniofacial malformations is comprehensive and does not allow to discuss all craniofacial malformations which have been described as single entities. Many... (Review)
Review
The field of craniofacial malformations is comprehensive and does not allow to discuss all craniofacial malformations which have been described as single entities. Many of the syndromes with craniofacial malformations are ultrarare. In this review we have chosen craniofacial malformation syndromes which are of relevance for the pediatrician, especially neonatologist: different types of craniosynostoses, oculo-auriculo-vertebral spectrum, Pierre Robin sequence and Treacher Collins syndrome. These syndromes will be described in detail. Diagnostic and therapeutic options will be discussed.
Topics: Abnormalities, Multiple; Craniosynostoses; Humans; Pierre Robin Syndrome
PubMed: 34561177
DOI: 10.1016/j.siny.2021.101290