Clinical and Serologic Responses After a Two-dose Series of High-dose Influenza Vaccine in Plasma Cell Disorders: A Prospective, Single-arm Trial

Abstract

Background: 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 and methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Immunity; Infections; Monoclonal gammopathy of undetermined significance; Multiple myeloma; Vaccination.

Figure 1. Serologic Response Rates

(A) Bar graph showing proportion of patients who achieved seroprotection against influenza B, H1N1, H3N2, and all 3 vaccine strains combined. First or second vaccination significantly increased rate of seroprotection against all 3 combined strains among patient group compared to baseline, p<0.001 (***). Second vaccination significantly boosted the rate of seroprotection compared with first vaccination, p<0.01 (*). (B) Bar graph showing proportion of patients who achieved seroconversion against influenza B, H1N1, H3N2, and all 3 vaccine strains combined. Second vaccination significantly boosted the rate of seroconversion compared with first vaccination, p=0.02 (*). Abbreviations: All 3, All three influenza strains included in the study vaccine; FluB, influenza B.

Figure 2. Correlates of Serologic Response

Forest plot illustrating effect of a group of risk factors on achieving (A) seroprotection (B) seroconversion among all patients or those with a plasma cell disorder requiring therapy (as opposed to asymptomatic/monoclonal gammopathy of undetermined significance). The x-axis is on log scale with base at 2. The filled black dot represents the estimates of the odds ratio regarding relevant risk factors. 95% confidence intervals are represented with the horizontal lines and vertical short lines at each end. P values associated with each risk factor are listed to the far right, p<0.05 (*) and p<0.005 (***). Abbreviations: plasma cell disorder, PCD; monoclonal gammopathy of undetermined significance, MGUS; intravenous immunoglobulin, IVIG; partial response, PR; immunoglobulins, Igs; immunomodulatory drug, IMID; odds Ratio, OR; lower 95% confidence interval, CLL; upper 95% confidence interval, CLU; p value, Prob.

Figure 3. Clinical Characteristics Associated with Lower Rates of Seroprotection

Bar graphs comparing rate of developing seroprotection against all 3 influenza vaccine strains between (A) Plasma cell disorder (PCD) patients requiring therapy versus those with asymptomatic/monoclonal gammopathy of undetermined significance; (B) patients with versus without suppression of uninvolved immunoglobulins; (C) PCD patients who were actively receiving conventional chemotherapy versus those who were not; (D) PCD patients with a disease response status less than partial response versus those with a partial response or better; and (E) patients who developed laboratory-confirmed respiratory viral infections other than influenza during the study period versus those who did not. Statistically significant comparisons are bracketed, p<0.001 (***), p<0.01(**), or p<0.05(*). Abbreviations: monoclonal gammopathy of undetermined significance, MGUS.