Randomized study comparing high-dose (HD) influenza vaccine to standard-dose (SD) influenza vaccine in patients with breast cancer age < 65 receiving chemotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21695-e21695
Author(s):  
Saad Jamshed ◽  
Ann R Falsey ◽  
Paul Thushara ◽  
Jennifer Walker ◽  
Edward E Walsh
Keyword(s):  
Breast Cancer ◽  
Influenza Vaccine ◽  
Standard Dose ◽  
Geometric Mean ◽  
Randomized Study ◽  
H3n2 Virus ◽  
High Dose ◽  
Curative Intent ◽  
Clinical Benefits ◽  
Robust Response

e21695 Background: Patients on chemotherapy often fail to develop a robust response to influenza vaccine. We had previously demonstrated that HD vaccine improved immunogenicity in cancer patients receiving chemotherapy. The present subgroup analysis evaluates immunogenicity & tolerability of HD to SD vaccine specifically in breast cancer pts <65 yrs receiving chemotherapy. Methods: 35 breast cancer pts were randomized to receive either SD or HD (17 vs 18) vaccine on day1 of chemotherapy during 2 influenza seasons. HAI titers were measured prior to & 4-wks after vaccination. HAI were summarized as geometric mean titer (GMT) and seroconversion (>4-fold titer rise) & seroprotection (GMT ≥40) rates calculated. t-test was used to compare log2-transformed GMT titers between groups and χ2 for comparison of seroconversion and seroprotection rates. Results: 2 pts were included only once (yr 1) as they received study vaccine both yrs. Mean age (50.4 vs 51.3 yrs) and baseline HAI titers were equivalent; 81 vs 88% were receiving therapy with curative intent in SD vs HD arms, respectively. Both vaccines were well tolerated with no SAEs. Post vaccination GMT were greater after HD vaccine, but was statistically significant only for H3N2 virus. Seroconversion rates for B strain was significantly improved with HD vaccine while seroprotection was excellent for all antigens in both arms. Conclusions: Trivalent HD influenza vaccine can be safely administered with increased seroconversion over SD vaccine. Most patients with breast cancer should be offered vaccination even if they are receiving chemotherapy, as they demonstrate robust response to either influenza vaccine. A larger study is needed to show clinical benefits with HD vaccine. Clinical trial information: NCT01666782. [Table: see text]

scholarly journals 2737. Comparison of Antibody Responses to Vaccination with a Pure Hemagglutinin Influenza Vaccine (rHA) and Licensed Subvirion Influenza Vaccine Made in Eggs or Cell Culture in Adults 60 Years and Older

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S963-S963
Author(s):  
Moumita Sarker ◽  
Angela Branche ◽  
Michael Peasley ◽  
David Topham
Keyword(s):  
Older Adults ◽  
Influenza Vaccine ◽  
Vaccine Development ◽  
Standard Dose ◽  
Geometric Mean ◽  
The United States ◽  
Antibody Responses ◽  
Influenza B Virus ◽  
Influenza B ◽  
High Dose

Abstract Background Influenza is associated with increased mortality and morbidity for older adults. High-dose egg grown trivalent inactivated influenza vaccine (Fluzone HD) is safe and provides superior immune responses in older adults compared with standard dose (SD). Recently, two new vaccines have been licensed in the United States: cell cultured inactivated vaccine FluCelVax and baculovirus-expressed pure hemagglutinin (HA) vaccine FluBlok. Data from one study demonstrated higher efficacy with FluBlok than SD Fluzone in older adults. There is no data however comparing HD Fluzone to FluBlok and FluCelVax has not been studied at all. The purpose of this study was to assess hemagglutinin inhibition (HAI) antibody responses to vaccination with three vaccines in adults ≥ 60 years. Methods Adults ≥ 60 years were randomly assigned to receive one of the three vaccines: Fluzone HD, FluBlok and FluCelVax (Figure 1). Active influenza-like illness (ILI) surveillance was conducted with bi-weekly telephone calls. Serum samples were collected prior to vaccination and at day 7, 14, 28 and 180 and antibody responses assessed by HAI titer to A/Singapore/INFIMH-16–0019(H3N2), A/Michigan/45/2015(H1N1) and B/Colorado/6/2017 (Victoria) viruses as well as a circulating H3N2 strain. The primary endpoint was a 4-fold rise in antibody titer at day 28. Results 48 subjects were vaccinated in October 2018. Mean age was 69 and 65% were female. Two subjects reported ILI symptoms and one was positive for infection (H1N1). A majority of subjects demonstrated pre-existing antibody to all three viruses (Figure 2, Blue). Geometric mean titers (GMT) for antibody responses to the influenza A viruses were similar for FluBlok (FB) and HD Fluzone (FZ) but lower for FluCelVax(FCB) subjects (Figure 2, Orange). A higher percent of FlubBlok subjects demonstrated 4-fold rise in antibody responses to the Victoria influenza B virus (FB GMT 140 vs. FZ GMT 116, P = 0.26). Conclusion In this small study, antibody responses were similar or higher in older adults after vaccination with FluBlok compared with Fluzone HD with lower responses demonstrated with FluCelvax. Emerging concerns about HA egg adaptation during vaccine development compels further study to determine the appropriate vaccination strategy for this vulnerable population. Disclosures All authors: No reported disclosures.

Continued consideration for high dose influenza vaccine in persons living with HIV

2019 ◽  
Vol 14 (9) ◽  
pp. 605-615
Author(s):  
Sin-Ling Jennings ◽  
Jessica Swiderek ◽  
Joshua R Sawyer ◽  
Raymond Cha
Keyword(s):  
Influenza Vaccine ◽  
Standard Dose ◽  
Geometric Mean ◽  
Risk Groups ◽  
High Dose ◽  
People Living With Hiv ◽  
Increased Risk ◽  
Persons Living With Hiv ◽  
Living With Hiv ◽  
Hemagglutinin Inhibition

High dose-inactivated influenza vaccine (HD IIV3) is currently recommended only for patients who are 65 or older, whereas other potential risk groups, such as people living with HIV, are excluded from this recommendation. There is a potential that persons living with HIV may be at an increased risk of complications secondary to influenza. HD IIV3 has been associated with increased rates of seroconversion, seroprotection and hemagglutinin inhibition geometric mean titers in comparison to standard dose-inactivated influenza vaccine in this population. Despite the major impact that combination antiretroviral therapy has on this population, further consideration of HD IIV3 may be valuable until virological suppression is widely achieved.

scholarly journals Gastrointestinal Events in High-Dose vs Standard-Dose Influenza Vaccine Recipients

2018 ◽  
Vol 5 (6) ◽  
Author(s):  
H Keipp Talbot ◽  
Andrew J Dunning ◽  
Corwin A Robertson ◽  
Victoria A Landolfi ◽  
David P Greenberg ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Influenza Vaccine ◽  
Randomized Clinical Trial ◽  
Standard Dose ◽  
High Dose ◽  
Passive Surveillance ◽  
Prospective Randomized Clinical Trial ◽  
Gastrointestinal Events ◽  
Gastrointestinal Adverse Events

Abstract Passive surveillance data had signaled the possibility of gastrointestinal adverse events occurring after the administration of high-dose inactivated influenza vaccine (IIV-HD). However, in a large, prospective randomized clinical trial, rates of serious gastrointestinal events were no greater among IIV-HD recipients than among those who received a standard-dose influenza vaccine.

Potential for Single High-Dose Influenza Immunization in Unprimed Children

PEDIATRICS ◽  
1982 ◽  
Vol 70 (6) ◽  
pp. 982-986 ◽  
Author(s):  
Peter A. Gross ◽  
Gerald V. Quinnan ◽  
Pureza F. Gaerlan ◽  
Carolyn R. Denning ◽  
Anne Davis ◽  
...  
Keyword(s):  
New York ◽  
Influenza A ◽  
Standard Dose ◽  
Geometric Mean ◽  
High Dose ◽  
York Metropolitan Area ◽  
Reaction Index ◽  
Number Of Patients ◽  
Sibling Control ◽  
High Concentrations

High concentrations of split-product vaccine (SPV) are more immunogenic than lower concentrations. These studies were verified with another influenza strain, B/Singapore/22/79. Two ether-treated SPVs were compared in 80 children and young adults. The vaccine strains were influenza A/Bangkok/79, A/Brazil/78, and B/Singapore /79; 44 patients received a high-dose SPV containing 7, 7, and 60 µg each of the respective hemagglutinins (HA) and 36 received a standard dose SPV containing 7, 7, and 7 µg of HA, respectively. Among persons initially seronegative by hemagglutination inhibition (HAI) tests, the geometric mean titer (GMT) in 15 recipients of one high dose was 97 vs GMT of 37 in 18 recipients of one standard dose (P &lt; .05). Furthermore, 87% of high-dose recipients had HAI titer ≥ 40 vs 44% of standard dose recipients. In initially seropositive persons, GMT in 29 recipients of one high dose was 170 vs GMT of 84 in 18 recipients of one standard dose (P &lt; .05). Immune response to the other two virus strains was comparable for the two vaccines. The reaction index for the high dose vaccine was 0.70 vs 0.45 for the standard dose (P = NS). An A/Bangkok epidemic struck the New York metropolitan area. The attack rate in unvaccinated matched sibling control subjects was 35% (15/43). There were no vaccine failures. In conclusion, in the small number of patients studied, a 60-µg HA dose of B/Singapore/79 was significantly more immunogenic than a standard 7-µg HA dose without an increase in reactogenicity.

scholarly journals Immunogenicity of high-dose influenza vaccination in patients with primary central nervous system malignancy

2018 ◽  
Vol 5 (3) ◽  
pp. 176-183
Author(s):  
Roy E Strowd ◽  
Gregory Russell ◽  
Fang-Chi Hsu ◽  
Annette F Carter ◽  
Michael Chan ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Influenza Vaccine ◽  
Elderly Patients ◽  
Influenza Vaccination ◽  
Standard Dose ◽  
High Grade Glioma ◽  
Cns Lymphoma ◽  
High Dose ◽  
Central Nervous System Malignancy

Abstract Background For cancer patients, rates of influenza-associated hospitalization and death are 4 times greater than that of the general population. Previously, we reported reduced immunogenicity to the standard-dose influenza vaccine in patients with central nervous system malignancy. In other poorly responding populations (eg, elderly patients), high-dose vaccination has improved efficacy and immunogenicity. Methods A prospective cohort study was designed to evaluate the immunogenicity of the Fluzone® high-dose influenza vaccine in brain tumor patients. Data on diagnosis, active oncologic treatment, and immunologic status (eg, CD4 count, CD8 count, CD4:CD8 ratio) were collected. All patients received the high-dose vaccine (180 µg). Hemagglutination inhibition titers were measured at baseline, day 28, and 3 months following vaccination to determine seroconversion (≥4-fold rise) and seroprotection (titer ≥1:40), which were compared to our prior results. Results Twenty-seven patients enrolled. Diagnoses included high-grade glioma (85%), CNS lymphoma (11%), and meningioma (4%). Treatment at enrollment included glucocorticoids (n = 8, 30%), radiation (n = 2, 7%), and chemotherapy (n = 9, 33%). Posttreatment lymphopenia (PTL, CD4 ≤ 200) was observed in 4 patients (15%). High-dose vaccination was well tolerated with no grade III-IV toxicity. Overall, seroconversion rates for the A/H1N1, A/H3N2, and B vaccine strains were significantly higher than in our prior study: 65% vs 37%, 69% vs 23%, and 50% vs 23%, respectively (all P < .04). Seroconversion was universally poor in patients with PTL. While seroprotection at 3 months declined in our prior study, no drop was observed following high-dose vaccination in this cohort. Conclusions The immunologic response to HD influenza vaccination was higher in this cohort than standard-dose influenza vaccination in our prior report. These findings mirror those in elderly patients where high-dose vaccination is the standard of care and raise the possibility of an immunosenescence phenotype.

scholarly journals Standard-dose versus high-dose radiotherapy with concurrent chemotherapy in esophageal cancer: A prospective randomized study

2018 ◽  
Vol 07 (01) ◽  
pp. 27-30 ◽  
Author(s):  
Navin Nayan ◽  
M. Bhattacharyya ◽  
Vikas K. Jagtap ◽  
A. K. Kalita ◽  
R. Sunku ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Total Dose ◽  
Standard Dose ◽  
Randomized Study ◽  
Complete Response ◽  
Concurrent Chemotherapy ◽  
Prospective Randomized Study ◽  
High Dose ◽  
Large Sample Size

Abstract Objective: The objective of this study is comparision of local and distant control rates with high-dose versus standard-dose radiotherapy along with concurrent chemotherapy in esophageal cancer – a prospective randomized study. Materials and Methods: Histologically proven Stage I–III patients with carcinoma esophagus were randomized into two groups. One group has been treated with standard-dose radiotherapy, i.e., a total dose of 50.4 Gy (1.8 Gy/day, 28#, 5 days/week). The other group (study arm) has received high-dose radiotherapy, i.e. a total dose of 64.8 Gy (1.8 Gy/day, 36#, 5 days/week). Both groups have received 2 cycles of 3 weekly concurrent chemotherapy (cisplatin 75 mg/m[2] on day 1 and 5-fluorouracil 750 mg/m[2] continuous intravenous infusion over 24 h on day 1–4). Follow-up response evaluation was done by both endoscopy and computed tomography scan after 6–8 weeks and after 2 months thereafter. Results: Out of a total of 28 patients, 68% showed a complete response, 14% showed partial response, and 18% patients developed progressive disease at first and subsequent follow up (median follow-up of 21 months). Among the complete response patients, rates were higher in high-dose group compared to standard-dose radiotherapy group (71% vs. 64%, P = 0.38). Treatment-related toxicities were acceptable in both groups. Conclusion: High-dose radiotherapy with concurrent chemotherapy seems to be more effective with acceptable toxicity in our study. However, further follow-up and large sample size may be required to validate the current study conclusion.

scholarly journals Double-Blind, Randomized, Placebo-Controlled Phase II Dose-Finding Study To Evaluate High-Dose Rifampin for Tuberculous Meningitis

2018 ◽  
Vol 62 (12) ◽  
Author(s):  
S. Dian ◽  
V. Yunivita ◽  
A. R. Ganiem ◽  
T. Pramaesya ◽  
L. Chaidir ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Tuberculous Meningitis ◽  
Standard Dose ◽  
Geometric Mean ◽  
Phase Iii ◽  
High Dose ◽  
Treatment Area ◽  
Double Blind ◽  
Time Curve

ABSTRACT High doses of rifampin may help patients with tuberculous meningitis (TBM) to survive. Pharmacokinetic pharmacodynamic evaluations suggested that rifampin doses higher than 13 mg/kg given intravenously or 20 mg/kg given orally (as previously studied) are warranted to maximize treatment response. In a double-blind, randomized, placebo-controlled phase II trial, we assigned 60 adult TBM patients in Bandung, Indonesia, to standard 450 mg, 900 mg, or 1,350 mg (10, 20, and 30 mg/kg) oral rifampin combined with other TB drugs for 30 days. The endpoints included pharmacokinetic measures, adverse events, and survival. A double and triple dose of oral rifampin led to 3- and 5-fold higher geometric mean total exposures in plasma in the critical early days (2 ± 1) of treatment (area under the concentration-time curve from 0 to 24 h [AUC0–24], 53.5 mg · h/liter versus 170.6 mg · h/liter and 293.5 mg · h/liter, respectively; P < 0.001), with proportional increases in cerebrospinal fluid (CSF) concentrations and without an increase in the incidence of grade 3 or 4 adverse events. The 6-month mortality was 7/20 (35%), 9/20 (45%), and 3/20 (15%) in the 10-, 20-, and 30-mg/kg groups, respectively (P = 0.12). A tripling of the standard dose caused a large increase in rifampin exposure in plasma and CSF and was safe. The survival benefit with this dose should now be evaluated in a larger phase III clinical trial. (This study has been registered at ClinicalTrials.gov under identifier NCT02169882.)

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