For Patients With Plasma Cell Disorders, Are Two Flu Vaccines Better Than One?

Patients with plasma cell disorders (PCDs) such as multiple myeloma (MM) have compromised immunity, and potent anti-cancer treatments further deplete immunity, making them highly susceptible to infections. Influenza infections represent a common morbidity, despite routine administration of seasonal flu vaccines, highlighting the need for better vaccination strategies for this population.

According to results from a randomized study presented at the 2017 ASH Annual Meeting, a strategy of a higher-antigen-dose flu vaccine followed by a booster shot prevented infection in most patients with PCDs and led to more durable protection against flu – even in the middle of flu season.

“We previously reported that a two-dose strategy of high-dose influenza vaccine is safely tolerated in patients with PCDs and associated with fewer laboratory-confirmed influenza infections,” reported lead author Andrew Branagan, MD, from the Cancer Center at Massachusetts General Hospital in Boston. But, he added, the extent of seroprotection was “unexpected.”

A total of 122 people were enrolled (median age = 67 years; range = 42-90 years) in this double-blind, randomized trial; 97 required therapy and 25 had asymptomatic gammopathy. Patients were randomized 2:1 to receive either two doses of high-dose influenza vaccination (separated by 30 days; n=74) or standard-of-care influenza vaccination (a single, age-based vaccination plus a saline placebo injection at 30 days; n=48).

To document the immunologic effects of this vaccination strategy, the researchers analyzed the serologic responses (via hemagglutination inhibition [HAI] titers) at four timepoints: baseline, 30 days following the initial vaccine, 30 days following the second vaccine, and at the end of the flu season (April 30).

Following the second vaccine (or saline placebo), rates of total seroprotection (against all three influenza vaccine strains, defined as HAI >40) were 86.3 percent for patients who received two high-dose vaccines, compared with 63.9 percent for those who received the standard vaccination (p<0.05).

A higher proportion of patients in the two-dose group had sustained seroprotection through the end of flu season (58.5% and 33.3%). “Rates of seroprotection trended toward significance at the end of the flu season against all three vaccine strains (p=0.07) and against the H3N2 strain (p=0.05), and were significantly higher against the H1N1 strain (p<0.05),” the authors reported. The seasonal H1N1 strain was the predominant circulating strain during the 2015 to 2016 flu season, they added.

“Unexpectedly, [our] analysis revealed that protective HAI antibody titers rapidly fall in patients [with PCD],” Dr. Branagan observed. “Typically, HAI titers slowly decrease following a peak protective response, but do not drop below protective levels until after six months.” In this study, patients began to lose HAI seroprotection within four months, and even as soon as 30 days.

These results suggest that a two-dose series of high-dose vaccine mitigates loss of vaccine-induced HAI titers, allowing for more durable serologic protection throughout the flu season.

Subgroup analyses found that patients on active intravenous immunoglobulin therapy and immunomodulatory therapy were more likely to have a serologic response to flu vaccination, while older, male, and more heavily pretreated patients were less likely to respond. The researchers noted, however, that the study was not large enough to adequately evaluate those associations. This trial also only explored responses to three influenza strains, which may limit the applicability of the results to other circulating strains of the influenza virus.

“Studies are ongoing to further explore immune function following influenza vaccination, including cell-mediated responses, and to define the optimal dose and timing of influenza vaccination in patients [with PCD],” Dr. Branagan concluded.

The authors report no financial conflicts.


Branagan A, Duffy E, Foster C, et al. Two dose series of high-dose influenza vaccine is associated with longer duration of serologic immunity in patients with plasma cell disorders. Abstract #438. Presented at the 2017 American Society of Hematology Annual Meeting, December 10, 2017; Atlanta, GA.