36 - Safety and Reactogenicity of the Adjuvanted Recombinant Zoster Vaccine after Allogeneic Hematopoietic Stem Cell Transplantation

Background: Herpes zoster (HZ) is common after allogeneic hematopoietic stem cell transplantation (HCT) and associated with high morbidity. While antiviral prophylaxis reduces incidence, increased risk remains after discontinuation and vaccination strategies are needed. A non-live adjuvanted recombinant zoster vaccine (RZV) has been developed but not yet studied in this population.

Methods: In this single center prospective observational cohort study, allogeneic HCT recipients ³18 years old and 9-24 months from HCT were eligible to receive 2 doses of RZV separated by ³8 weeks as part of revised institutional vaccination guidelines. The primary endpoint was safety and reactogenicity in the total vaccinated cohort (TVC). The secondary endpoints were incidence and severity of chronic graft versus host disease (cGVHD) in the TVC compared to historical controls and incidence rates of HZ in the TVC and modified total vaccinated cohort (mTVC).

Results: Of the 158 participants (mean age 55 years, 91 [58%] male) in the TVC, 150 (95%) received second vaccine. 92.1% had solicited reactions with 87.3% injection site reactions (18.7% grade 3) and 82.8% general reactions (26.5% grade 3). In the subgroup receiving first vaccine at 9-12 months after HCT, cumulative incidence of cGVHD was similar to historical controls at predefined time points between 9-15 months (unadjusted incidence rate ratio [IRR] 1.1 [95% CI 0.84-1.44], adjusted IRR 1.05 [95% CI 0.8-1.38]); there was also no difference in severity of cGVHD, or incidence of death or disease relapse. There were 4 (2.5%) HZ cases during the study period with IR 28.34/1000 person-years over median follow up 281 days (IQR 190, 354) in the mTVC. All cases occurred after antiviral prophylaxis discontinuation and one case resulted in death.

Conclusion: Two doses of RZV after allogeneic HCT was safe and acceptable despite high rates of reactogenicity. There was no evidence of an increase in cGVHD, relapse, or death compared to historical controls and overall low rates of breakthrough HZ similar to those reported after autologous HCT. Immunogenicity studies and placebo-controlled trials are needed to determine vaccine response and efficacy so that timing of RZV and its potential impact on discontinuation of antiviral prophylaxis can be determined.