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those with PMBCL who received or did not receive radiation
therapy (p=0.39).
The three patients who experienced disease progression had
advanced-stage disease. One patient with GZL achieved CR after
autologous HCT, and two patients with PMBCL have responded
to immunotherapy after salvage chemotherapy failure.
These outcomes in the frontline setting “are encouraging and
warrant further investigation, especially in patients with PMBCL,”
the authors concluded.
The study is limited by its small patient population and lack
of a comparator arm.
The corresponding authors report financial support from Bristol-
Myers Squibb, Seattle Genetics, Merck, Kite, Pharmacyclics, Celgene,
Takeda, Curis, Immunogen, and Incyte.
REFERENCE
Svoboda J, Landsburg DJ, Dwivedy Nasta S, et al. Brentuximab vedotin with
R-CHP chemotherapy as frontline treatment for patients with CD30 positive
primary mediastinal large B-cell, diffuse large B-cell, and grey zone lymphomas:
results of a phase I/II multisite trial. Abstract #191. Presented at the 2017
American Society of Hematology Annual Meeting, December 9, 2017; Atlanta, GA.
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 administra-
tion 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.”
The findings were presented at the 2017 ASH Annual Meeting.
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 fol-
lowing influenza vaccination, including cell-mediated responses,
and to define the optimal dose and timing of influenza vaccina-
tion in patients [with PCD],” Dr. Branagan concluded.
The authors report no financial conflicts.
REFERENCE
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.
March 2018
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