Session: 905. Outcomes Research: Non-Malignant Conditions Excluding Hemoglobinopathies: Poster III
Hematology Disease Topics & Pathways:
Research, Health outcomes research, Clinical Research, Diseases, Immune Disorders, Real-world evidence, Treatment Considerations, Biological therapies, White blood cell disorders, Monoclonal Antibody Therapy
Methods: Searches to identify case reports and observational cohort studies were conducted in MEDLINE (via PubMed) and Embase, and supplemented with desktop searches using Google, to identify original articles (11/4/2015–10/31/2023) and conference abstracts (1/1/2021–10/31/2023) published in or translated to English. Other studies such as meta-analyses, clinical trials, and editorials were excluded. Selected publications were screened by up to three researchers, and included data on pts with HES and outcomes associated with anti-IL-5/Rα treatment. Where reported, study characteristics and data on pt demographics, clinical characteristics, treatments, and outcomes were collected for this descriptive analysis. The definition of improved organ involvement varied, but commonly included reported improvements in symptoms or laboratory test results.
Results: In total, data were collected from 55 case reports (N=70) and five cohort studies (N=195): Kuang, 2018 (S1, N=35), Aalbers, 2022 (S2, N=15), Chen, 2022 (S3, N=123), Caminati, 2023 (S4, N=11), and Papajoannou, 2023 (S5, N=11). Of the pts from case reports, mean (standard deviation [SD]) age at diagnosis (n=68) was 38.5 (23.7) years, 40% (n=28/70) were female, and 67.2% (n=39/58) had idiopathic HES. Of the pts from cohort studies (N=195), median age ranged from 44–62 years, 33–63% were female, and 46–100% had idiopathic HES. Prior to initial anti-IL-5/Rα treatment (baseline) in case reports and cohort studies, HES manifestations were most common in dermatological (0–77%) and pulmonary (0–74%) systems. Overall, 46 pts started on benralizumab, and 211 pts started on mepolizumab, which is approved in HES.
In case reports from baseline to post-initial anti-IL-5/Rα treatment, with a mean follow-up time of 39 weeks, mean (SD) blood eosinophil (bEOS) counts by treatment type were reduced from: overall (n=37), 7445 (15128) to 409 (1264) cells/µL (p=0.0066); benralizumab (n=10), 7410 (11866) to 58 (183) cells/µL (p=0.0824); mepolizumab (n=26), 7711 (16646) to 560 (1486) cells/µL (p=0.0340). After initial anti-IL-5/Rα treatment, bEOS counts in pts from cohort studies (reported in S1, S4, and S5 only) were reduced by 53–100% over 12–48 weeks.
In case reports, 55.1% of pts (n=38/69) had improved organ involvement and nearly all pts (n=69/70) had improved symptoms after initiating anti-IL-5/Rα treatment; improved organ involvement was most common in renal (67%) and neurological (40%) systems. In cohort studies, HES organ involvement data after initiating anti-IL-5/Rα treatment were reported in S2 and S3 only. In S2 (N=15), 87% of pts on benralizumab experienced clinically relevant improvement in organ function after 22 months. For pts in S3 on mepolizumab (n=103) and benralizumab (n=15), 60% and 67% of pts, respectively, experienced an overall improvement in HES organ involvement.
In cohort studies that reported disease flares (S1, S2, S4, and S5 only), the majority of pts receiving mepolizumab or benralizumab had no or reduced HES flares, including asthma flares. One pt from S2 on benralizumab stopped treatment due to refractory disease. In S1, pts on mepolizumab alone had significantly fewer mean flares per year (0.19) versus pts on conventional treatment (7.03) or mepolizumab plus another treatment (0.96; p<0.05). In pts from case reports, five had hematological relapse and 13 had HES flares, including 12 pts on mepolizumab (n=54) and one pt on benralizumab (n=13). Oral corticosteroid (OCS) dose was reduced by ≥50% in 41% of pts from case reports, and in 50–100% of pts from cohort studies.
Conclusion: Use of anti-IL-5/Rα treatments in pts with HES is associated with significantly reduced bEOS counts, improved HES organ manifestations and symptoms, fewer HES flares, and reduced OCS dose.
Disclosures: Jain: AstraZeneca: Current Employment, Current holder of stock options in a privately-held company. Rowell: AstraZeneca: Current Employment, Current holder of stock options in a privately-held company; Roche: Current holder of stock options in a privately-held company. Edmonds: AstraZeneca: Current Employment, Current holder of stock options in a privately-held company. Stokes: Evidera: Current Employment, Other: Employed by Evidera who received consulting fees for this work from AstraZeneca. Ding: Evidera: Current Employment, Other: Employed by Evidera who received consulting fees for this work from AstraZeneca. Chen: AstraZeneca: Current Employment, Current holder of stock options in a privately-held company.
OffLabel Disclosure: This abstract contains information from case studies/series and cohort studies on the real-world use and impact of benralizumab in patients, which has not yet been approved for the treatment of hypereosinophilic syndrome.