REPORTING FROM THE 2018 BMT TANDEM MEETINGS
SALT LAKE CITY (FRONTLINE MEDICAL NEWS) – A recently approved adjuvanted herpes zoster vaccine)(Shingrix) effectively and safely prevented herpes zoster in a population of patients with multiple myeloma and other hematologic malignancies who received autologous hematopoietic stem cell transplantation.
The use of recombinant varicella zoster virus glycoprotein E in combination with an adjuvant system gives immunosuppressed individuals who have received hematopoietic stem cell transplantation (HSCT) a safe option for prevention of herpes zoster (HZ), said Javier de la Serna, MD, PhD, speaking at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.
Previously, only a live-attenuated varicella zoster vaccine had been available, making prolonged acyclovir prophylaxis the only safe HZ prevention strategy in this population.
Presenting the findings at a late-breaking abstract session, Dr. de la Serna said that for the 1,721 participants in a placebo-controlled multicenter trial who received both doses of the vaccine, the incidence of HZ for vaccine recipients was 3.0%, compared with 9.4% of placebo recipients, for a vaccine efficacy of 68.2% (95% confidence interval, 55.6-77.5; P less than 0.0001). These results met the study’s primary objective.
Postherpetic neuralgia (PHN) prevention efficacy – a secondary endpoint – was 89.3% for those receiving the vaccine (HZ/su); the incidence of PHN was 0.5% in the HZ/su study arm, compared with 4.9% for those who received placebo (95% CI, 22.5-99.8). The study also tracked other HZ complications as a secondary endpoint, finding efficacy of 77.8% (95% CI, 19.1–95.0). “The vaccine was highly efficacious in preventing all the secondary outcomes,” said Dr. de la Serna of the Hospital Universitario 12 de Octubre, Madrid.
The randomized, observer-blind phase 3 trial was conducted in 28 countries.Adults who received autologous HSCT were randomized 1:1 to receive HZ/su (n = 922) or placebo (n = 924) within 50-70 days of their transplant. Patients were excluded if they were expected to receive more than 6 months of anti–varicella zoster prophylaxis posttransplant, Dr. de la Serna said.
Participants received the first dose of HZ/su at the first study visit, and the second dose 30-60 days later. Patients were seen 1 month after the last vaccine dose, and then again at months 13 and 25, with telephone follow-up between the later visits. All participants were followed for at least 1 year, Dr. de la Serna said.
Episodes of HZ were confirmed by polymerase chain reaction assay, or, when samples were lacking or indeterminate, by agreement of at least three members of an ascertainment committee.
Of the two components of the HZ/su vaccine, glycoprotein E triggers both humoral immunity and activity of varicella zoster–specific CD4+ T cells; the adjuvant system – dubbed ASO1 – boosts immune response. The vaccine was approved by the Food and Drug Administration in October 2017 for use in adults aged 50 years and older.
In addition to the primary endpoint of vaccine efficacy in prevention of HZ cases during the study period, secondary objectives included monitoring vaccine reactogenicity and safety, and evaluating vaccine efficacy for the prevention of PHN and other complications of HZ.
Tertiary objectives included vaccine efficacy in preventing HZ during the first year posttransplant (vaccine efficacy 84.7%; 95% CI, 32.2-96.6), as well as efficacy in preventing hospitalizations related to HZ (vaccine efficacy 76.2%, 95% CI 61.1-86.0).
An exploratory analysis found vaccine efficacy of 71.8% for participants younger than 50 years (95% CI, 38.8 – 88.3). For patients aged 50 years and older, vaccine efficacy was 67.3% (95% CI, 52.6–77.9).
The safety of HZ/su was determined by analyzing data for all participants, but efficacy data included only those who received the second dose and did not develop HZ within a month of receiving the second vaccine dose.
In the efficacy group (n = 1,721), patients were mostly (n = 1,296) aged 50 years or older. Most patients (n = 937) received HSCT for multiple myeloma. Overall, participants were about 63% male, and 77% were of Caucasian/European ancestry.
Adverse events, solicited for the first 7 days after injections, were mostly mild and related to the local site pain and inflammation expected with an adjuvanted vaccine; HZ/su recipients also experienced more fatigue and muscle aches than did those receiving placebo. Median duration of symptoms was up to 3 days, with grade 3 events lasting up to 2 days.
Unsolicited and serious adverse events were similar between study arms, with a median safety follow-up period of 29 months. The investigators judged that no deaths were related to the vaccine, and there were no signals for increased rate of relapse or immune-mediated diseases.
The study was funded by GlaxoSmithKline; HZ/su(Shingrix) is marketed by GlaxoSmithKline. Dr. de la Serna reported being on the advisory board or receiving honoraria from multiple pharmaceutical companies.
SOURCE: de la Serna J et al. 2018 BMT Tandem Meetings, Abstract LBA2 .