Immunogenicity and Safety of an Adjuvanted Herpes Zoster Subunit Candidate Vaccine in Adults with Hematologic Malignancies: A Phase III, Randomized Clinical Trial

Abstract

Abstract Background Hematologic malignancy (HM) patients receiving immunosuppressive cancer therapy (ICT) are at increased risk of herpes zoster (HZ). Currently, no HZ vaccine is indicated for immunocompromised patients. The HZ subunit vaccine candidate (HZ/su), containing recombinant varicella zoster virus glycoprotein E and AS01B Adjuvant System, showed >90% efficacy and an acceptable safety profile in immunocompetent adults in all age groups ≥50 years. Here we report HZ/su immunogenicity and safety in HM adults ≥18 years of age who completed or are undergoing ICT. Methods In this phase III, observer-blind, multicenter study (NCT01767467), participants were randomized 1:1 to receive HZ/su or placebo (2 doses, 1–2 months apart) ≥10 days pre- or post-ICT. Humoral and cell-mediated immunogenicity (CMI) were assessed. The co-primary immunogenicity objectives were to evaluate HZ/su vaccine response rate and compare the immune response to HZ/su and placebo in participants excluding those with non-Hodgkin B-cell lymphoma (NHBCL) or chronic lymphocytic leukemia (CLL) at 1 month post-dose 2 (M2). Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days after each dose, respectively. Serious AEs (SAEs), disease-related events and potential immune-mediated diseases (pIMDs) were recorded throughout the study. Partial safety results up to 6 months post-dose 2 are shown (partially blinded, ongoing study). Results Of 562 participants (283 HZ/su 283; placebo 279), (mean age 57.3 [HZ/su 56.8; placebo 57.8] years), 415 were included in the according-to-protocol (ATP) cohort for humoral immunogenicity and 132 in the ATP sub-cohort for CMI. M2 immune responses were higher in the HZ/su group (Table 1). Both co-primary immunogenicity objectives were met (Figure 1). The most frequent local and general solicited AEs were pain and fatigue, reported by 48.2% and 47.8% of all participants (per-group data remain blinded). The frequency of unsolicited AEs, SAEs and pIMDs in the 2 groups was similar (Table 2). Conclusion HZ/su induced robust humoral and cellular immune responses at M2 in HM adults excluding NHBCL and CLL, who completed or are undergoing ICT. No safety concerns were observed up to 6 months post-dose 2. Funding GlaxoSmithKline Biologicals SA Disclosures L. Oostvogels, GSK group of companies: Employee and Shareholder, Salary and Shares