Dissertation/Thesis Abstract

Developing a More Effective Influenza Vaccination Strategy for Patients with Plasma Cell Disorders
by Branagan, Andrew R., Ph.D., Yale University, 2019, 95; 27541613
Abstract (Summary)

Patients with plasma cell disorders are highly susceptible to infections, including influenza, which are a major source of morbidity and mortality. Seasonal influenza vaccination is routinely administered to patients with plasma cell disorders, yet influenza infections remain common. Prior clinical trials suggest that serologic responses following standard influenza vaccination are very poor and occur in less than 20% of patients. Combining the use of higher antigen dose and a booster strategy, I hypothesized that serologic response rates could be improved in this patient population.

In Aim 1, I designed a pilot clinical trial (SHIVERING Trial) utilizing a two-dose series of high-dose influenza vaccine in plasma cell disorder patients (separated by 30 days). I conducted this trial at Smilow Cancer Center, New Haven, CT, during the 2014-2015 influenza season. Fifty-one patients were enrolled and received both doses of vaccines. This study demonstrated that this vaccine strategy was well tolerated in patients with plasma cell disorders. Serologic response rates also improved following the second high-dose influenza vaccine. Additionally, identified risk factors were associated with lower likelihood of serologic responses, including older age, more advanced disease, or active alkylator chemotherapy.

In Aim 2, I designed a randomized, double-blind, placebo controlled clinical trial (SHIVERING 2 Trial) to compare this two-dose series of high-dose influenza vaccination strategy to standard-of-care influenza vaccination in patients with plasma cell disorders. I conducted the trial Smilow Cancer Center, New Haven, CT and other cancer center affiliate locations within CT during the 2015-2016 flu season. Standard of care influenza vaccination was considered single, age-based vaccination (standard dose <65 years and high-dose ≥ 65 years) and patients in this arm received a saline placebo injection at 30 days. Serologic responses were analyzed by standardized procedure at four time points; baseline, 30 days following the initial vaccine, 30 days following the second vaccine, and at the end of the flu season. 122 total plasma cell disorder patients were enrolled. Following the second vaccine / placebo, rates of total seroprotection were significantly higher for patients who received two high dose vaccines versus standard vaccination. At the end of the flu season, rates of total seroprotection were significantly higher for patients who received two high dose vaccines versus standard vaccination. Risk factors were confirmed from the pilot trial, which were associated with lower likelihood of serologic responses.

In summary, I studied a new influenza vaccination strategy over two consecutive influenza seasons proving, for the first time, that high rates of serologic responses are possible in patients with plasma cell disorders. A two doses series of high dose influenza vaccine separated by 30 days is well tolerated in patients with plasma cell disorders. Results of a randomized, placebo-controlled, clinical trial demonstrated improved rates of seroprotection and seroconversion in plasma cell disorder patients following two high dose influenza vaccines compared to those receiving standard vaccination. Additionally, I evaluated the seasonal durability of serologic responses to influenza vaccine for the first time in PCD patients. Results suggest that protective HAI antibody titers rapidly fall in PCD patients. Interestingly, two dose series of high-dose influenza vaccine may mitigate loss of vaccine-induced HAI titers and allow more durable serologic protection throughout the influenza season. Identified risk factors suggest that certain subgroups of PCD patients, particularly those with more advanced disease, have even lower likelihood of serologic responses to influenza vaccination. This new vaccination strategy is safe and affordable and represents a viable option for PCD patients across a variety of treatment settings and stages of disease. As overall survival has increased for patients with plasma cell disorders, there will likely be more patients at later stages of disease with additional risk factors for influenza infections. Additional studies are needed to develop better strategies to prevent influenza as well as other infections in this high-risk patient population.

Indexing (document details)
Advisor: Dhodapkar, Madhav
Commitee: Lee, Alfred, Shaw, Albert, Shapiro, Eugene
School: Yale University
Department: Investigative Medicine
School Location: United States -- Connecticut
Source: DAI-B 81/10(E), Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Immunology, Oncology
Keywords: High-dose influenza vaccine, Influenza vaccine, Monoclonal gammopathy of undetermined significance, Multiple myeloma, Plasma cell disorders, Waldenstrom's macroglobulinemia
Publication Number: 27541613
ISBN: 9798607315894
Copyright © 2020 ProQuest LLC. All rights reserved. Terms and Conditions Privacy Policy Cookie Policy
ProQuest