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Original Investigation
July 9, 2019

Effect of Recombinant Zoster Vaccine on Incidence of Herpes Zoster After Autologous Stem Cell Transplantation: A Randomized Clinical Trial

Author Affiliations
  • 1GlaxoSmithKline, Wavre, Belgium
  • 2Hospital Universitario 12 de Octubre, Madrid, Spain
  • 3GlaxoSmithKline, Rixensart, Belgium
  • 4CureVac AG, Tübingen, Germany
  • 5University Hospital of Montpellier, Montpellier, France
  • 6Hospital Ramón y Cajal, Madrid, Spain
  • 7Ege University Medical School, Izmir, Turkey
  • 8Charles University Hospital, Prague, Czech Republic
  • 9Rambam Health Care Campus, Haifa, Israel
  • 10Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts
  • 11Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy
  • 12Chonnam National University Hwasun Hospital, Jellanamdo, Republic of Korea
  • 13University of Kansas Cancer Center, Westwood
  • 14Hospital Clínico Universitario, School of Medicine, University of Valencia, Valencia, Spain
  • 15Centro Integral Oncológico Clara Campal (CIOCC), Universidad CEU San Pablo, Madrid, Spain
  • 16Weill Medical College of Cornell University, New York, New York
  • 17Department of Hematology and Oncology, Charité University Medical Center, Berlin, Germany
  • 18Preventive Medicine and Epidemiology Department, University Hospital Vall d’Hebron, Barcelona, Spain
  • 19Haematology Department, Manchester University NHS Foundation Trust, Manchester Royal Infirmary, Manchester, England
  • 20Faculty of Biology, Medicine and Health, School of Medical Science, Division of Cancer Sciences, University of Manchester, Manchester, England
  • 21Hospital de Donostia, San Sebastián, Spain
  • 22Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, Catholic University of Korea, Seoul, South Korea
  • 23Hospital Ampang, Selangor, Malaysia
  • 24Royal Hobart Hospital, Hobart, Australia
  • 25Department of Clinical Haematology, Austin Health, Heidelberg, Australia
  • 26Fred Hutchinson Cancer Research Center, Seattle, Washington
  • 27Halozyme Therapeutics, San Diego, California
  • 28University of Pennsylvania, Philadelphia
  • 29Duke University Medical Center, Durham, North Carolina
JAMA. 2019;322(2):123-133. doi:10.1001/jama.2019.9053
Key Points

Question  What is the efficacy of 2 doses of the adjuvanted recombinant zoster vaccine in preventing herpes zoster in immunocompromised patients after autologous hematopoietic stem cell transplantation?

Findings  In this randomized clinical trial of 1846 patients who had undergone autologous hematopoietic stem cell transplantation, 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.

Meaning  A 2-dose course of recombinant zoster vaccine reduced the incidence of herpes zoster in autologous stem cell transplant recipients.

Abstract

Importance  Herpes zoster, a frequent complication following autologous hematopoietic stem cell transplantation (HSCT), is associated with significant morbidity. A nonlive adjuvanted recombinant zoster vaccine has been developed to prevent posttransplantation zoster.

Objective  To assess the efficacy and adverse event profile of the recombinant zoster vaccine in immunocompromised autologous HSCT recipients.

Design, Setting, and Participants  Phase 3, randomized, observer-blinded study conducted in 167 centers in 28 countries between July 13, 2012, and February 1, 2017, among 1846 patients aged 18 years or older who had undergone recent autologous HSCT.

Interventions  Participants were randomized to receive 2 doses of either recombinant zoster vaccine (n = 922) or placebo (n = 924) 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.

Main Outcomes and Measures  The primary end point was occurrence of confirmed herpes zoster cases.

Results  Among 1846 autologous HSCT recipients (mean age, 55 years; 688 [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 (95% CI, 0.22-0.44; P < .001), equivalent to 68.2% vaccine efficacy. Of 8 secondary end points, 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; placebo, n=13; IRR, 0.22; 95% CI, 0.04-0.81; P = .02) and in duration of severe worst herpes zoster–associated pain (vaccine, 892.0 days; placebo, 6275.0 days; hazard ratio, 0.62; 95% CI, 0.42-0.89; P = .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: 11%). Unsolicited and serious adverse events, potentially immune-mediated diseases, and underlying disease relapses were similar between groups at all time points.

Conclusions and Relevance  Among adults who had undergone autologous HSCT, a 2-dose course of recombinant zoster vaccine compared with placebo significantly reduced the incidence of herpes zoster over a median follow-up of 21 months.

Trial Registration  ClinicalTrials.gov Identifier: NCT01610414

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