Format

Send to

Choose Destination
JAMA. 2019 Jul 9;322(2):123-133. doi: 10.1001/jama.2019.9053.

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

Author information

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

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.

PMID:
31287523
DOI:
10.1001/jama.2019.9053

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center