RESUMO
INTRODUCTION: Asthma encompasses a spectrum of phenotypes often categorized into two groups- type 2 high (T2 high) and type 2 low (T2 low). T2 high includes atopic and eosinophilic presentations whereas T2 low is non-atopic, non-eosinophilic, and oft associated with neutrophilic inflammation. Eosinophilic asthma is often driven by IgE, IL-4, IL-5, and IL-13 and TSLP. This can lead to eosinophilic inflammatory response in the airways which in turn can be used as target for treatment. AREAS COVERED: The article will focus on biologic therapy that is currently being used in eosinophilic asthma management in mainly the adult population including clinical trials and co-morbidities that can be treated using the same biologics. A review on asthma biologics for pediatric population has been reviewed elsewhere. EXPERT OPINION: Biological therapy for asthma targeting the IgE, IL-4, IL-5, IL-13, and TSLP pathways are shown to have benefit for the treatment of eosinophilic asthma, as exemplified in real-world studies. When choosing the right biological agent factors such as phenotype, comorbidities, and cost-effectiveness of the biologic agent must be taken into consideration.
Assuntos
Asma , Terapia Biológica , Humanos , Asma/tratamento farmacológico , Asma/imunologia , Eosinofilia/imunologia , Eosinofilia/tratamento farmacológico , Antiasmáticos/uso terapêutico , Imunoglobulina E/imunologia , Produtos Biológicos/uso terapêutico , Eosinófilos/imunologia , Eosinófilos/efeitos dos fármacos , Eosinófilos/metabolismo , Citocinas/imunologia , Citocinas/antagonistas & inibidores , Citocinas/metabolismoRESUMO
Background: Leptomeningeal disease (LMD) is a devastating complication for patients with advanced cancer. Diagnosis and monitoring the response to therapy remains challenging due to limited sensitivity and specificity of standard-of-care (SOC) diagnostic modalities, including cerebrospinal fluid (CSF) cytology, MRI, and clinical evaluation. These hindrances contribute to the poor survival of LMD patients. CNSide is a CLIA-validated test that detects and characterizes CSF-derived tumor cells and cell-free (cf) DNA. We performed a retrospective analysis on the utility of CNSide to analyze CSF obtained from advanced non-small cell lung cancer (aNSCLC) patients with suspected LMD treated at the Huntsman Cancer Institute in Salt Lake City, UT. Methods: CNSide was used to evaluate CSF from 15 patients with aNSCLC. CSF tumor cell quantification was performed throughout treatment for 5 patients. CSF tumor cells and cfDNA were characterized for actionable mutations. Results: In LMD-positive patients, CNSide detected CSF tumor cells in 88% (22/25) samples versus 40% (10/25) for cytology (matched samples). CSF tumor cell numbers tracked response to therapy in 5 patients where CNSide was used to quantify tumor cells throughout treatment. In 75% (9/12) of the patients, genetic alterations were detected in CSF, with the majority representing gene mutations and amplifications with therapeutic potential. The median survival for LMD patients was 16.1 m (5.2-NR). Conclusions: We show that CNSide can supplement the management of LMD in conjunction with SOC methods for the diagnosis, monitoring response to therapy, and identifying actionable mutations unique to the CSF in patients with LMD.