Background: MPM is a highly aggressive pleural tumor associated with asbestos exposure and with limited survival despite systemic therapy. In previously treated patients ( p), no-randomized studies of immunotherapy (ICI) have demonstrated activity, and Checkmate 743 demonstrated survival benefit of ICI in first line with some differences according to histology. The objective of this study is to characterize the impact of ICI use on survival in p diagnosed with MPM at our institution. Methods: We review 189 MPM p diagnosed at Vall d'Hebron University Hospital between November 2002 and April 2020. Associations between clinical variables and outcome were assessed with Cox regression models and survival data were calculated by the Kaplan-Meier method. Results: Patient's characteristics: median age 68 years (y) (45-88 y), males: 70%, performance status (PS)1: 69%, asbestos exposure: 74%, epithelioid subtype: 76%. First line chemotherapy was offered to 85% of p (66% cisplatin-pemetrexed and 27% carboplatin-pemetrexed) and 19 p were treated in clinical trials in first line. Median progression free survival (PFS) was 4.4 months (m;CI95% 3.1-5.4). Median survival (OS) in overall population was 21.3 m (95%CI17.2-24.3). Epithelioid histology, PS 0, neutrophil-lymphocyte ratio >5 and treatment with cisplatin vs. carboplatin were associated with significant improvements in OS. In second line 27 p were treated with ICI in clinical trials. Median OS for p treated with ICI was 22.6 m (95%CI 11.1-34). No differences in PFS and OS for p treated with ICI were detected according to histology. Median PFS 2.7 m in epithelioid and 3 m in no-epithelioid (HR0.7, p = 0.43 CI95% 0.3-1.7) and OS 28.3 m in epithelioid and 13.8 m in noepithelioid (HR3.4 p = 0.01 CI95% 1.3-8.7). When we considered the OS of p treated with ICI from the time of initiation of the ICI, the median OS for epithelioid p was 12.4 m vs. 6.18 m for no epithelioid (HR2.1, p = 0.09 CI95% 0.8-5.2). Conclusions: In our series, ICI was an acceptable option for previously treated MPM patients. We confirmed histology is a prognostic factor with better OS for p with epithelioid tumors. However, we could did not demonstrate histology is a predictive factor for efficacy of ICI.
Identification of clinical phenotypes and biomarkers, like eosinophilia, allows tailoring treatment of severe asthma.Benralizumab, an IL-5-Receptor a monoclonal antibody, presented good results in clinical trials, but real-life evidence is still small due to its recent approval.
METHODS:Retrospective study of patients with severe eosinophilic asthma with at least 2 exacerbations in the previous year, despite optimized treatment, treated with Benralizumab in a University Hospital (national approval since 2019).RESULTS: 13 patients with severe eosinophilic asthma were identified. Benralizumab was the chosen therapy in 5 patients, including 3 females and 2 males, with mean age 60 years-old. The mean duration of follow-up was 12 months. 1 patient had previously been treated with Omalizumab without improvement.Relevant asthma comorbidities included obesity (60%), rhinosinusitis (40%), gastroesophageal reflux disease (40%), depression/anxiety (40%) and bronchiectasis (20%).Selected patients presented uncontrolled symptoms and a median of 4 AE 1 exacerbations in the previous year, with asthma motivating emergency room visits in 3 patients and hospitalization in 1 case.In the 12 months preceding biologic treatment, 80% of patients received two or more courses of oral corticosteroids (median 4 AE 2) and 60% had two or more antibiotic cycles. All patients reported daily use of reliever medication, despite high dose ICS and at least two other controller medication.Baseline mean blood eosinophil count was 1260/mL and total IgE was 305 IU/mL. 4 patients had an obstructive ventilatory defect, namely one very severe and one moderately severe.During treatment with Benralizumab none of the patients experienced new exacerbations or required oral corticosteroids. Use of reliever medication was reduced in 40% of patients.The eosinophil count was reduced to zero in all patients. Regarding lung function, 2 patients showed an improvement over 200 mL in FEV1.There were no significant adverse effects of anti-IL-5Ra treatment.CONCLUSIONS: Treatment with Benralizumab led to complete reduction in exacerbations and oral corticosteroids courses, with some benefit in reliever use and lung function.CLINICAL IMPLICATIONS: This study describes a local clinic experience with a recently approved drug and, despite the small cohort, illustrates the real-life benefit of anti-IL-5Ra treatment.
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