A Randomized Trial of Two 2-Dose Influenza Vaccination Strategies for Patients Following Autologous Hematopoietic Stem Cell Transplantation

Abstract

Background Seroprotection and seroconversion rates are not well understood for 2-dose inactivated influenza vaccination (IIV) schedules in autologous haematopoietic stem cell transplantation (autoHCT) patients. Materials/methods A randomised single-blind controlled trial of IIV in autoHCT patients in their first year post-transplant was conducted. Patients were randomised 1:1 to high dose (HD) IIV followed by standard dose (SD) vaccine (HD-SD arm) or two SD vaccines (SD-SD arm), 4 weeks apart. Haemagglutination inhibition (HI) assay for IIV strains was performed at baseline, 1, 2 and 6 months post-first dose. Evaluable primary outcomes were seroprotection (HI titre ≥40) and seroconversion (4-fold titre rise) rates and secondary outcomes: geometric mean titres (GMT), GMT ratios (GMR), adverse events, influenza-like-illness (ILI) and laboratory-confirmed influenza (LCI) rates and factors associated with seroconversion. Results Sixty-eight patients were enrolled (34 per arm) with median age of 61.5 years, majority male (68%) with myeloma (68%). Median time from autoHCT to vaccination was 2.3 months. For HD-SD and SD-SD arms, percentage of patients achieving seroprotection was 75.8% and 79.4% for H1N1, 84.9% and 88.2% for H3N2 (all p>0.05) and 78.8% and 97.1% for influenza-B/Yamagata (p=0.03), respectively. Seroconversion rates, GMT and GMR, number of ILI or LCIs were not significantly different between arms. Adverse event rates were similar. Receipt of concurrent cancer therapy was independently associated with higher odds of seroconversion (OR 4.3, 95% CI 1.2-14.9, p=0.02). Conclusions High seroprotection and seroconversion rates against all influenza strains can be achieved with vaccination as early as 2 months post-autoHCT with either two-dose vaccine schedules.

Immunogenicity of COVID-19 vaccines in patients with hematologic malignancies: a systematic review and meta-analysis

“…International health bodies now recommend third COVID-19 vaccine doses in immune compromised patients including haematological malignancy 72,73 . Heterologous prime-boost or use of high dose vaccine formulations have been utilised in randomised trials of seasonal influenza vaccination in haematology and HCT patient with mixed success 17,74 . In addition, other preventative approaches such as the use of anti-SARS-CoV-2 monoclonal antibody therapy as pre exposure (NCT04625725) and post exposure prophylaxis require further evaluation in vulnerable patient groups who respond poorly to vaccination 75 .…”

“…Serological responses are classically utilised as surrogate end points for clinical efficacy in clinical trials of vaccination in patients with haematological malignancy [15][16][17] . Serological thresholds for protection (seroprotection) following vaccination have been established for infections such as seasonal influenza 17 .…”

“…Serological responses are classically utilised as surrogate end points for clinical efficacy in clinical trials of vaccination in patients with haematological malignancy [15][16][17] . Serological thresholds for protection (seroprotection) following vaccination have been established for infections such as seasonal influenza 17 . In the majority of studies included in this review, however, the outcome of interest was seropositivity as defined by antibody levels above the detection threshold.…”

“…Understanding the impact of COVID-19 vaccines on cancer patients is critical as social distancing restrictions are being eased in countries with relatively high rates of vaccination coverage 14 . Assessing immune response post-vaccination is the basis of many vaccination studies in patients with haematological malignancy and is often utilised as a surrogate marker of vaccine efficacy [15][16][17] . These studies are the basis for vaccination recommendations contained within international guidelines 18,19 .…”

Humoral response to mRNA‐based COVID‐19 vaccine in patients with myeloid malignancies

“… 15 , 16 , 17 , 18 , 19 , 20 , 21 While a serological response is not the only predictor of immunity, it has been used as a surrogate marker of vaccine efficacy in many vaccination studies in patients with haematological malignancies because a low serological level could make this population more vulnerable to COVID‐19. 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 …”