Herpes zoster is a frequent complication following autologous haematopoietic stem cell transplantation (HSCT) and associated with significant morbidity. A non-live adjuvanted recombinant zoster vaccine has been developed to prevent post-transplantation zoster. In a randomised clinical trial of 1846 patients, the incidence of herpes zoster over a median follow-up of 21 months was 30 per 1000 person-years after 2 recombinant zoster vaccine doses vs 94 per 1000 person-years after placebo. This difference was statistically significant. The results are published on 9 July 2019 in JAMA.
To assess the efficacy and adverse event profile of the recombinant zoster vaccine in immunocompromised autologous HSCT recipients, the ZOE-HSCT Study Group Collaborators performed a phase III, randomised, observer-blinded study (NCT01610414) in 167 centres in 28 countries among patients aged 18 years or older who had undergone recent autologous HSCT.
Participants were randomised to receive 2 doses of either recombinant zoster vaccine or placebo administered into the deltoid muscle. The first dose was given 50 to 70 days after transplantation and the second dose 1 to 2 months thereafter. The study primary endpoint was occurrence of confirmed herpes zoster cases.
Among 1846 autologous HSCT recipients (mean age, 55 years; 37% women) who received 1 vaccine or placebo dose, 1735 (94%) received a second dose and 1366 (74%) completed the study.
During the 21-month median follow-up, at least 1 herpes zoster episode was confirmed in 49 vaccine and 135 placebo recipients (incidence, 30 and 94 per 1000 person-years, respectively), an incidence rate ratio (IRR) of 0.32 (p < 0.001), equivalent to 68.2% vaccine efficacy.
Of 8 secondary endpoints, 3 showed significant reductions in incidence of postherpetic neuralgia (vaccine, n=1; placebo, n=9; IRR, 0.1; p = 0.02) and of other prespecified herpes zoster–related complications (vaccine, n=3; placebo, n=13; IRR, 0.22; p = 0.02) and in duration of severe worst herpes zoster–associated pain (vaccine, 892.0 days; placebo, 6275.0 days; hazard ratio, 0.62; p = 0.01). Five secondary objectives were descriptive.
Injection site reactions were recorded in 86% of vaccine and 10% of placebo recipients, of which pain was the most common, occurring in 84% of vaccine recipients (grade 3 in 11%). Unsolicited and serious adverse events, potentially immune-mediated diseases, and underlying disease relapses were similar between groups at all time points.
The study team concluded that among adults who had undergone autologous HSCT, a 2-dose course of recombinant zoster vaccine significantly reduced the incidence of herpes zoster over a median follow-up of 21 months.
Bastidas A, de la Serna J, El Idrissi M, et al. Effect of Recombinant Zoster Vaccine on Incidence of Herpes Zoster After Autologous Stem Cell Transplantation: A Randomized Clinical Trial. JAMA 2019;322(2):123-133. doi:10.1001/jama.2019.9053.