乌鸦传媒

Patients who underwent autologous hematopoietic stem cell transplantation (HSCT) and received the recombinant herpes zoster vaccine (Shingrix) had a lower incidence of the illness compared with HSCT patients receiving placebo, a randomized trial found.

During a median 21 months of follow-up, there was at least one herpes zoster case confirmed in 49 patients who received the vaccine and in 135 patients who received placebo (incidence rate ratio 0.32, 95% CI 0.22-0.44, P<0.001), for a vaccine efficacy of 68.2%, reported Keith M. Sullivan, MD, of Duke University in Durham, North Carolina, and colleagues.

Those randomized to receive the vaccine also had reduced incidence of herpes zoster complications and duration of herpes zoster-associated pain, they wrote in .

Alison Freifeld, MD, of the University of Nebraska Medical Center in Omaha, said that this study has some important implications, because while transplant patients were typically always given a zoster vaccine, the old vaccine couldn't be administered until at least 2 years after transplantation, according to the guidelines, due to the possibility of developing disseminated vaccine strain live virus in an immunocompromised patient.

"The advantage of Shingrix is it is an inactivated viral component vaccine with excellent immunogenicity," Freifeld, who was not involved in the study, told 乌鸦传媒. "It's a great advantage for autologous transplant patients because it permits the vaccine to be given much earlier than the previous live virus vaccine."

Researchers conducted the phase III Zoster Efficacy Study in Patients Undergoing HSCT (ZOE-HSCT) in 167 centers in 28 countries from July 2012 to February 2017. Eligible adults had undergone autologous HSCT in the past 50-70 days, but were excluded if they had been vaccinated against herpes zoster or varicella the previous year, or had HIV infection.

Participants were randomized 1:1 to receive either recombinant zoster vaccine or placebo in two 0.5 ml doses -- the first being 50-70 days following HSCT procedure and the second 1 to 2 months later. Primary endpoint was defined as occurrence of confirmed herpes zoster cases between first dose and the end of the study.

Overall, 1,864 autologous HSCT recipients received at least one dose of the vaccine. They were a mean age of 55, and a little over a third were women. The most common underlying diagnosis was multiple myeloma (53%), and the authors noted that similar portions of patients in both groups received bortezomib (Velcade), a targeted therapy to treat multiple myeloma and mantle cell lymphoma.

There were 184 herpes zoster cases in the modified vaccine cohort, for an incidence of 30 per 1,000 person years in the vaccine group and 94 per 1,000 in the placebo group, respectively.

In an email to 乌鸦传媒, Jeanne Marrazzo, MD, of the University of Alabama at Birmingham, who was also not involved with the research, characterized the findings as "very persuasive evidence" that this vaccine can protect against reactivation of varicella zoster virus.

"Interestingly, the protection was less than that observed in immune-competent people, which the investigators attribute to a generally weaker immune system in the HSCT recipients," she said. "Regardless, this outcome is considerably better than no vaccine, which was the earlier alternative!"

Secondary endpoints examined herpes zoster-related complications for the vaccine group versus the placebo group, including:

• Herpes zoster-related complications, excluding postherpetic neuralgia (IRR 0.22, 95% CI 0.04-0.81, P=0.02)
• Postherpetic neuralgia (IRR 0.11, 95% CI 0.00-0.78, P=0.02)
• Hospitalizations (HR 0.15, 95% CI 0.03-0.68, P=0.01)
• Reduction of duration of worst herpes zoster-associated pain during disease episodes (HR 0.62, 95% CI 0.42-0.89, P=0.01)

Examining adverse events, 86% of the vaccine group and 10% of the placebo group reported injection site reactions. Pain occurred in 84% of vaccine recipients, and 11% reported grade 3 pain. There were five adverse events in the vaccine group judged to be vaccine-related (neutropenia, immune thrombocytopenic purpura, cutaneous vasculitis, arthralgia, and atrial fibrillation), while four serious adverse events were reported in the placebo group.

Citing the 86% of patients who experienced adverse events, Marrazzo added, "the study also reminds us that the majority of people who get this new vaccine will experience notable local side effects."

There were 118 and 124 fatal serious adverse events in the vaccine and placebo groups, respectively, during the course of the study, mainly due to recurring malignancy and non-herpes zoster infections, Sullivan and colleagues said. In the year following the study, 13 people in the vaccine group and eight in the placebo group reported at least one event of potentially immune-mediated disease, the authors said.

Study limitations included the fact that the authors did not assess long-term protection beyond the second year.

Freifeld also pointed out that the vaccine still needs to be assessed in allogeneic transplant patients and solid organ transplant patients, who are typically more profoundly immunosuppressed and may not have the same reactogenicity as an autologous transplant patient might have following the procedure.

"Whether those groups would benefit in terms of earlier administration following transplant remains to be seen," she said. "But for the autologous group, this report does represent a landmark because of the ability to prevent cases of zoster earlier after transplantation."

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