ASH 2017 | Two flu vaccines are better than one for most patients with plasma cell disorders

The MM Hub is delighted to be reporting from the 59th American Society of Hematology (ASH) Annual Meeting held in Atlanta, Georgia, from 9-12 December 2017. On Sunday, 10 December 2017, an oral abstract session was held and entitled: Session: 653. Myeloma: Therapy, excluding Transplantation: Upfront Therapy for Multiple Myeloma: Induction and Maintenance. During this session, an oral abstract was presented by Andrew Branagan from The Cancer Center, Massachusetts General Hospital, Boston, MA. The title of the talk (Abstract 438) was: Two Dose Series of High-Dose Influenza Vaccine Is Associated with Longer Duration of Serologic Immunity in Patients with Plasma Cell Disorders.

Dr. Branagan began his talk by explaining how patients with plasma cell disorders (PCDs) are highly prone to infections and that this is a major cause of morbidity, despite preventative measures such as seasonal vaccines. In order to improve immunity in these patients, Branagan and colleagues have trialed several strategies such as increasing the influenza vaccine to a two-dose series, along with higher antigen doses. In order to effectively document the effects of such a strategy, the serologic readout in PCD patients was followed over a single flu season.

Key Highlights:

• Double-blind, randomized clinical trial established during the 2015-16 flu season
• Patients (pts) were divided into a 2:1 ratio and given either: two doses of Fluzone® High-Dose influenza vaccination (separated by 30 days) or a single standard of care (SOC) influenza vaccination (age-based: standard dose <65 years and high-dose ≥ 65 year) with a saline placebo at 30 days
• Pts were eligible if they had any PCD and no contraindication to influenza vaccine
• Hemagglutination inhibition (HAI) titers were analyzed at baseline, then 30 days after the first and second vaccine, and at the end of the flu season (30^th April)
• PCD pts (n = 122) were enrolled: PCD pts = 97 with disease and 25 asymptomatic gammopathy
• Median age = 67 years (range 42-90)
• Two doses of High-Dose vaccine = 74 pts; SOC plus placebo = 48 pts

Data is given as Two doses of High-Dose vaccine vs SOC plus placebo:

• Seroprotection rate after second vaccine or placebo: 86.3% vs 63.9%
• Seroprotection rate at end of flu season: 58.5% vs 33.3%
• Seroprotection against all vaccine strains (HAI >40):
  • Base >40: 26.8% vs 26.2%, Day 30 >40: 73.2% vs 83.8%, Day 60 >40: 63.9% vs 87.5% (p=0.05), End of season (EOS) >40: 33.3% vs 58.5% (p=0.07)
• Pts receiving the two-dose vaccine had significantly higher rates of total seroprotection following the second vaccine (p<0.05) compared to those receiving SOC plus placebo
• Seroprotection was more significant against all 3 vaccine strains (HAI >40) (p=0.07) and notably, high protection remained against the H3N2 strain (p=0.05) (major circulating strain of this season), and especilly high against the H1N1 strain, the major circulating strain of the season (p<0.05) 
• PCD pts lost seroprotection within 4 months and in some cases within 30 days

Dr. Branagan concluded his talk by emphasizing that a two-dose flu vaccination separated by 30 days is well tolerated and associated with high rates of seroprotection and seroconversion. Serial measurement of antibody titers for the first time in PCD patients reveal rapid and significant loss of protection during one flu season. The use of two high-dose vaccinations drives more durable responses in PCD patients and should be considered as part of the SOC regimens for these patients. Subgroups of patients were identified based on the likelihood of serologic response, with a lower likelihood for; older age, male sex, disease remission status worse than partial response (PR), increased prior lines of therapy and active alkylating agent chemotherapy. A higher likelihood was linked to higher IVIG therapy and IMiD therapy. Dr. Branagan concluded that additional studies are required in patients with PCDs with clinical endpoints. Studies are continuing in his lab with regards to further understanding the timing, kinetics and optimal doses of the vaccine required, with possible knock-on effects for other vaccines in immunologically challenged patients.