Tandem high-dose influenza vaccination is associated with more durable serologic immunity in patients with plasma cell dyscrasias

• Type of Material: Article
• Authors: Andrew R Branagan, Yale Cancer Center, New Haven; Eamon Duffy, Yale Cancer Center, New Haven; Geliang Gan, Yale School of Public Health; Fangyong Li, Yale Sch Publ Hlth; Connor Foster, Yale Cancer Center, New Haven; Rakesh Verma, Yale Cancer Center, New Haven; Lin Zhang, Yale Cancer Center, New Haven; Terri L Parker, Yale Cancer Center, New Haven; Stuart Seropian, Yale Cancer Center, New Haven; Dennis L Cooper, Yale Cancer Center, New Haven; Debra Brandt, Yale Cancer Center, New Haven; Jeremy Kortmansky, Yale Cancer Center, New Haven; Davit Witt, Yale Cancer Center, New Haven; Thomas M Ferencz, Yale Cancer Center, New Haven; Kavita Dhodapkar, Emory University; Madhav Dhodapkar, Emory University
• Language: English
• Date: 2021-03-09
• Publisher: ELSEVIER
• Publication Version: Final Published Version
• Copyright Statement: © 2021 by The American Society of Hematology
• Final Published Version (URL): http://dx.doi.org/10.1182/bloodadvances.2020003880
• Title of Journal or Parent Work: BLOOD ADVANCES
• Volume: 5
• Issue: 5
• Start Page: 1535
• End Page: 1539
• Grant/Funding Information: This trial was supported by the Arthur Sekerak Cancer Fund. A.R.B. is supported by the American Society of Hematology Clinical Research Scholar Award and the National Center for Advancing Translational Sciences, National Institutes of Health (UL1 TR000142). M.V.D. is supported in part by funds from the National Cancer Institute, National Institutes of Health (R35 CA197603), and Specialized Center of Research Award from the Leukemia and Lymphoma Society. Sanofi provided influenza vaccine and performed HAI titer assays.
• Keywords: Life Sciences & Biomedicine; IMMUNOGENICITY; SEASONAL INFLUENZA; RESPONSES; EFFICACY; SINGLE; Hematology; MYELOMA; Science & Technology

Abstract

Patients with plasma cell dyscrasias (PCDs) experience an increased burden of influenza, and current practice of single-dose annual influenza vaccination yields suboptimal protective immunity in these patients. Strategies to improve immunity to influenza in these patients are clearly needed. We performed a randomized, double-blind, placebo-controlled clinical trial comparing tandem Fluzone High-Dose influenza vaccination with standard-of-care influenza vaccination. Standard-of-care vaccination was single-dose age-based vaccination (standard dose,,65 years; high dose, $65 years), and patients in this arm received a saline placebo injection at 30 days. A total of 122 PCD patients were enrolled; 47 received single-dose standard-of-care vaccination, and 75 received 2 doses of Fluzone High-Dose vaccine. Rates of hemagglutinin inhibition (HAI) titer seroprotection against all 3 strains (H1N1, H3N2, and influenza B) were significantly higher for patients after tandem high-dose vaccination vs control (87.3% vs 63.2%; P 5.003) and led to higher seroprotection at the end of flu season (60.0% vs 31.6%; P 5.04). These data demonstrate that tandem high-dose influenza vaccination separated by 30 days leads to higher serologic HAI titer responses and more durable influenza-specific immunity in PCD patients. Similar vaccine strategies may also be essential to achieve protective immunity against other emerging pathogens such as novel coronavirus in these patients. This trial was registered at www.clinicaltrials.gov as #NCT02566265.