New Form of Herpes Zoster Vaccine Shows Promise in Autologous HSCT Patients

Herpes zoster (HZ) can be a common complication in patients who have undergone an autologous hematopoietic stem cell transplantation (HSCT) and can be associated with significant morbidity. However, a newer form of a HZ vaccine was able to reduce outbreaks among this patient population in a recently published study led by Duke Health.

"Among HSCT patients, [an HZ] outbreak is often more feared than the transplant itself, and I've had patients tell me they'd undergo 2 transplants before facing another episode of shingles," study author Keith Sullivan, MD, the James B. Wyngaarden Professor of Medicine at Duke, said in a press release.

The nonlive adjuvanted recombinant vaccine, GSK1437173A, was developed with the intention of preventing post-transplant incidence of HZ.

To evaluate the vaccine, the research team initiated a phase 2, randomized, observer-blind, multicenter study in 28 countries. The study was conducted from July 13, 2012, through February 1, 2017, and enrolled 1846 participants aged 18 years and older who had undergone recent autologous HSCT. The findings of the study were published in JAMA.

At the point of enrollment, participants were randomized 1:1 to receive 2 doses of the recombinant HZ vaccine or placebo administered into the deltoid muscle. In total, 922 participants were enrolled into the recombinant zoster group and 924 were placed in the placebo group. Participants in both groups received the first dose 50-70 days post-transplantation and the second dose was administered 1 to 2 months following the initial dose.

Of the 1846 participants who were enrolled into the study, the mean age was 55 years and 37% of the study population were women. A total of 1735 (94%) participants received a second dose and 1266 (74%) participants completed the study.

The primary end point of the study was occurrence of confirmed HZ cases and, during the 21-month median follow-up period, the investigators documented at least 1 HZ episode in 49 participants in the vaccine group (incidence: 30 per 1000 person-years) and 135 participants in the placebo group (incidence: 94 per-1000 person-years). The authors report an incidence rate ratio (IRR) of 0.32 (95% CI, 0.22-0.44; P < .001), which is equivalent to 68.2% vaccine efficacy.

The investigators indicate that of the 8 secondary end points that were assessed “3 showed significant reductions in incidence of postherpetic neuralgia (vaccine, n = 1; placebo, n = 9; IRR, 0.1; 95% CI, 0.00-0.78; P = .02) and of other prespecified herpes zoster-related complications (vaccine, n = 3, placeb0, n = 13; IRR, 0.22; 95% CI, 0.04-0.81; P = .02) and in duration of severe worst HZ-associated pain (vaccine, 892.0 days; placebo, 6275.0 days; hazard ratio, 0.62; 95% CI, 0.42-0.89; P = .01).”

According to the report, injection site reactions were documented in 86% of vaccine recipients and 10% of placebo recipients, respectively. The most common reaction was injection-site pain, which was reported in 84% of vaccine recipients. Additionally, the article indicates that “unsolicited and serious adverse events, potentially immune-mediated diseases and underlying disease relapses were similar between groups at all times.”

One limitation of this research is that the study did not compare incidence of HZ-related complications, with the exception of postherpetic neuralgia and hospitalization. Additional limitations include no assessment of long-term protection beyond the second year and no data on pre-transplantation varicella zoster virus serology were collected from the participants.

Despite these limitations, the investigators conclude that among patients with a history of autologous HSCT, receiving 2-doses of the recombinant zoster vaccine was able to reduce the incidence of HZ over a median follow-up of 21 months when compared with placebo.

According to Sullivan, not only is this trial an important discovery for autologous HSCT recipients, but it could have potential to play a role in preventing HZ in other vulnerable patient populations.

"This trial is important because it demonstrates that the vaccine works in severely immunosuppressed patients," Sullivan said in the press release. "That suggests it could also work with others whose immune systems are not normal—including patients with HIV, breast cancer, and auto-immune conditions."