Early vaccination of autologous hemopoietic stem-cell transplant (auto-HSCT) recipients during the peri-transplant period can be effective for the prevention of infections such as herpes zoster and the vaccine is well tolerated, according to a study published in the Lancet.
Drew J Winston, MD, from the Department of Medicine at the University of California Los Angeles Medical Center, and colleagues, conducted a randomized, double-blind, placebo-controlled phase 3 trial, to establish the efficacy and safety of an inactivated varicella zoster vaccine for the prevention of herpes zoster after auto-HSCT. Patients were recruited from 135 stem-cell transplant centers and hospitals and were 18 years or older, scheduled to receive an auto-HSCT within 60 days of enrollment, and had a history of varicella infection or were seropositive for antibodies to varicella zoster virus, or both.
Patients were randomly assigned according to a central randomization schedule to receive either the inactivated-virus vaccine from 1 of 3 consistency lots, a high-antigen lot, or placebo, stratified by age (<50 vs ≥50 years) and intended duration of antiviral prophylaxis after transplantation (≤3 months vs >3 to ≤6 months). Patients were given 4 doses of inactivated vaccine or placebo, with the first dose 5 to 60 days before auto-HSCT, and the second, third, and fourth doses at about 30, 60, and 90 days after transplantation.
The primary efficacy end point was the incidence of herpes zoster, confirmed by PCR or adjudication by a masked clinical committee, or both, assessed in all participants randomly assigned to the vaccine consistency lot group or placebo group who received at least one dose of vaccine and had auto-HSCT.
Between Dec 7, 2010, and April 25, 2013, 560 patients were randomly assigned to the vaccine group, 106 to the high-antigen group, and 564 to the placebo group. A total of 249 (44%) of patients in the vaccine consistency lot group, 35 (33%) in the high-antigen lot group, and 220 (39%) in the placebo group discontinued before study end due to mortality or withdrawal. A total of 51 patients were excluded from the primary efficacy end point analyses because they did not undergo auto-HSCT or were not vaccinated, or both (22 [4%] in the vaccine consistency lot group, and 29 [5%] in the placebo group). Mean follow-up for efficacy was 2.4 years in the vaccine consistency lot group and 2.3 years in the placebo group.
A total of 42 (8%) of 538 patients in the vaccine consistency lot group and 113 (21%) of 535 in the placebo group had a confirmed case of herpes zoster; estimated vaccine efficacy was 63.8%. For the combined vaccine groups vs the placebo group, the proportion of patients with serious adverse events (216 [33%] of 657 vs 181 [33%] of 554; risk difference 0.2%) and serious vaccine-related adverse events (5 [1%] vs 5 [1%]; risk difference 0.1%) was similar. Vaccine-related injection site adverse events occurred more frequently in participants given vaccine than in those given placebo (191 [29%] vs 36 [7%]; risk difference 2.6%).
“This study shows for the first time in a large phase 3 trial that early vaccination of auto-HSCT recipients during the peri-transplant period can be effective for the prevention of an opportunistic infection like herpes zoster and that the vaccine is well tolerated,” the authors concluded.
Winston DJ, Mullane KM, Cornely OA, et al. Inactivated varicella zoster vaccine in autologous haemopoietic stem-cell transplant recipients: an international, multicentre, randomised, double-blind, placebo-controlled trial [published online May 24, 2018]. Lancet. doi: 10.1016/S0140-6736(18)30631-7