Clinical and Serologic Responses After a Two-dose Series of High-dose Influenza Vaccine in Plasma Cell Disorders: A Prospective, Single-arm Trial.
Patients with multiple myeloma (MM) and other plasma cell disorders are highly susceptible to influenza infections, which are major causes of morbidity in this population, despite the routine administration of a seasonal influenza vaccination. Existing data are limited by small and retrospective studies, which suggest poor seroprotection rates of < 20% after standard influenza vaccination in patients with MM.



Patients with plasma cell dyscrasia (n = 51) were treated with a 2-dose series of high-dose inactivated trivalent influenza vaccine during the 2014 to 2015 influenza season. Laboratory-confirmed influenza infections were identified through seasonal surveillance, sera were collected for influenza hemagglutination antibody inhibition (HAI) titer assays, and logistic regression models were used to identify the clinical correlates to the HAI serologic responses.



Influenza vaccine was well tolerated, without any vaccine-related grade ≥ 2 adverse events. Only 3 patients (6%) experienced laboratory-confirmed influenza. The rates of HAI seroprotection against all 3 vaccine strains (A/California/7/2009 [H1N1] pdm09-like virus; A/Texas/50/2012 [H3N2]-like virus; and a B/Massachusetts/2/2012-like virus) increased from 4% at baseline to 49% and 65% after 1 and 2 doses, respectively. The risk factors associated with a lower likelihood of HAI serologic response included plasma cell disorder requiring therapy, less than a partial response found on disease response assessment, and active conventional chemotherapy. Alternatively, active therapy with an immunomodulatory drug alone or with a proteasome inhibitor was associated with a greater likelihood of an HAI serologic response.



These data have demonstrated that, in contrast to the historically poor results with standard influenza vaccination, this novel high-dose booster vaccination strategy leads to high rates of seroprotection. Randomized controlled studies are needed to compare this novel strategy to the standard vaccination strategy.
Yale Cancer Center, New Haven, CT; Yale School of Medicine, New Haven, CT. Electronic address: Andrew.branagan@yale.edu.
Andrew R
AR
Branagan
Yale School of Medicine, New Haven, CT.
Eamon
E
Duffy
Icahn School of Medicine at Mount Sinai, New York, NY.
Randy A
RA
Albrecht
Yale Cancer Center, New Haven, CT; Yale School of Medicine, New Haven, CT.
Dennis L
DL
Cooper
Yale Cancer Center, New Haven, CT; Yale School of Medicine, New Haven, CT.
Stuart
S
Seropian
Yale Cancer Center, New Haven, CT; Yale School of Medicine, New Haven, CT.
Terri L
TL
Parker
Yale School of Public Health, New Haven, CT.
Geliang
G
Gan
Yale School of Public Health, New Haven, CT.
Fangyong
F
Li
Yale School of Public Health, New Haven, CT.
Daniel
D
Zelterman
Yale Cancer Center, New Haven, CT; Yale School of Medicine, New Haven, CT.
Chandra Sekhar
CS
Boddupalli
Yale Cancer Center, New Haven, CT; Yale School of Medicine, New Haven, CT.
Lin
L
Zhang
Yale Cancer Center, New Haven, CT; Yale School of Medicine, New Haven, CT.
Rakesh
R
Verma
Yale Cancer Center, New Haven, CT.
Thomas M
TM
Ferencz
Yale Cancer Center, New Haven, CT; Yale School of Medicine, New Haven, CT.
Madhav V
MV
Dhodapkar
D000368:Aged; D005260:Female; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology*; D010865:Pilot Projects; D008258:Waldenstrom Macroglobulinemia / Q000276:immunology
D007252:Influenza Vaccines
Immunity; Infections; Monoclonal gammopathy of undetermined significance; Multiple myeloma; Vaccination