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.

Brigham and Women's Hospital Dana Farber Cancer Institute Boston Massachusetts

Centro Integral Oncológico Clara Campal Universidad CEU San Pablo Madrid Spain

Charles University Hospital Prague Czech Republic

Chonnam National University Hwasun Hospital Jellanamdo Republic of Korea

CureVac AG Tübingen Germany

Department of Clinical Haematology Austin Health Heidelberg Australia

Department of Hematology and Oncology Charité University Medical Center Berlin Germany

Department of Internal Medicine Seoul St Mary's Hospital College of Medicine Catholic University of Korea Seoul South Korea

Department of Translational Medicine University of Eastern Piedmont Novara Italy

Duke University Medical Center Durham North Carolina

Ege University Medical School Izmir Turkey

Faculty of Biology Medicine and Health School of Medical Science Division of Cancer Sciences University of Manchester Manchester England

Fred Hutchinson Cancer Research Center Seattle Washington

GlaxoSmithKline Rixensart Belgium

GlaxoSmithKline Wavre Belgium

Haematology Department Manchester University NHS Foundation Trust Manchester Royal Infirmary Manchester England

Halozyme Therapeutics San Diego California

Hospital Ampang Selangor Malaysia

Hospital Clínico Universitario School of Medicine University of Valencia Valencia Spain

Hospital de Donostia San Sebastián Spain

Hospital Ramón y Cajal Madrid Spain

Hospital Universitario 12 de Octubre Madrid Spain

Preventive Medicine and Epidemiology Department University Hospital Vall d'Hebron Barcelona Spain

Rambam Health Care Campus Haifa Israel

Royal Hobart Hospital Hobart Australia

University Hospital of Montpellier Montpellier France

University of Kansas Cancer Center Westwood

University of Pennsylvania Philadelphia

Weill Medical College of Cornell University New York New York

JAMA. 2019 Aug 27;322(8):785. doi: 10.1001/jama.2019.11467. PubMed

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ClinicalTrials.gov
NCT01610414