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

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 = .003) and led to higher seroprotection at the end of flu season (60.0% vs 31.6%; P = .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.

Humoral immunogenicity of the seasonal influenza vaccine before and after CAR-T-cell therapy

“…4,23,37,40,41,48 As patients are often hospitalized during this period, the finding might be particularly relevant for respiratory virus outbreaks with nosocomial transmission like influenza and SARS-CoV-2. 52,53 Overall, these findings are consistent with observations of relatively impaired vaccine immunogenicity in individuals being treated for hematologic malignancies or who received a HCT, with influenza vaccine response rates between 0%-60%, 11,15,16,[54][55][56][57] but still indicate sufficient immunogenicity to support vaccination.…”

How to Provide the Needed Protection from COVID-19 to Patients with Hematologic Malignancies

“…This may reflect the enrollment being skewed to patients who had been previously successfully treated for acute leukemia and low enrollment of patients on active chemotherapy, and the use of non-B cell toxic therapies for the treatment of patients with CML, MDS and AML. Experience with similar low seroconversion rates in patients with hematologic malignancies when receiving vaccinations for other viral infections, in particular when on certain therapies (26), has led to the testing of higher doses of the vaccine, different formulations, and repeated rounds of immunization (27,28). During the COVID-19 pandemic, some patients without seroconversion after receiving the full initial vaccination have received subsequent immunizations (sometimes referred to as boosters, but may not be the adequate term for persons who did not respond to the first set of vaccination).…”

Viral Immunity and Vaccines in Hematologic Malignancies: Implications for COVID-19

“…As an example, suboptimal immunogenicity of influenza vaccines in myeloma patients has led to studies exploring the use of high-dose vaccines as well as repeat dosing (7). In a randomized study, two injections of high-dose vaccine led to higher overall rates of seroprotection compared with the current standard of single vaccines in patients with plasma cell disorders (8). This strategy also led to more durable immunity with a higher likelihood of seroprotection at the end of study.…”