Safety and Immunogenicity of Heat-Treated Zoster Vaccine (ZVHT) In Adults with Hematologic Malignancy (HM).

Abstract

AbstractAbstract 1394 BackgroundHerpes zoster incidence is higher in patients undergoing chemotherapy for hematologic malignancy [HM] (25-100 cases/1000 person-years) than in the general population (≂f3-5 cases/1000 person-years) and the general older adult population (7-12 cases/1000 person-years). The licensed live-attenuated zoster vaccine was heat-treated [ZVHT] and assessed in adults with HM. MethodsRandomized, double-blind, placebo-controlled, multicenter Phase I study of 4 ZVHT doses (≂f30 days apart) in adults ≥18 years with HM. Eighty subjects were enrolled, of whom 61 received ZVHT and 19 placebo (Pbo). Blood was collected at baseline and ≂f28 days after each dose to measure (1) VZV antibody concentrations by glycoprotein enzyme-linked immunosorbent assay (gpELISA), and (2) varicella zoster virus (VZV) T-cell responses by interferon-gamma enzyme-linked immunospot (IFN-γ ELISPOT) assay. All vaccinated patients were evaluated for adverse events (AEs) through day 28 postdose 4.The primary hypothesis was that 4 doses of ZVHT would elicit a statistically significant VZV-specific immune response (lower bound of 90% CI on geometric mean fold rise [GMFR] >1.0) in adults with HM. ResultsInjection-site adverse events (AEs) occurred in 31.1% of the ZVHT group and 10.5% of the Pbo group. Of overall vaccine-related systemic AEs (ZVHT: 18.0%, Pbo: 15.8%), only nausea was reported by >10% in either group (ZVHT: 0.0%, Pbo: 10.5%). There were 2 reported vaccine-related serious AEs in the ZVHT group (vomiting, 2 days postdose 1; peripheral neuropathy, 6 days postdose 2). Four AEs resulting in death were reported in the ZVHT group (coronary arteriosclerosis, 24 days postdose 1; malignant neoplasm, 18 days postdose 2; leukemia, 10 days postdose 2; neutropenic sepsis, 48 days postdose 2), all deemed not vaccine-related by the investigator. Two subjects discontinued due to vaccine-related AEs (peripheral neuropathy, ZVHT 6 days postdose 2; nausea and vomiting, Pbo 2 days postdose 1). No ZVHT recipient had a rash that was PCR positive for the vaccine strain of VZV.At baseline, the VZV-specific gpELISA GMT was 205 (90% CI: 158, 267) and the IFN-γ ELISPOT GMC was 11 (90% CI: 7, 18). Both measures increased Postdose 4: gpELISA GMT was 262 (90% CI: 204, 336); IFN-γ ELISPOT GMC was 24 (90% CI: 14, 41). The primary hypothesis was met, as Postdose 4 immune responses were significantly higher than baseline for both gpELISA (GMFR=1.3 [90% CI: 1.1, 1.5], p=0.003) and IFN-γ ELISPOT (GMFR= 2.2 [90% CI: 1.4, 3.5], p=0.004). ConclusionIn the HM population, ZVHT had an acceptable safety profile and elicited statistically significant VZV-specific antibody and functional T-cell responses at 28 days Postdose 4. Disclosures:Camacho:Merck: Research Funding. Off Label Use: This clinical research study examined the safety and immunogenicity of a heat-treated version of the licensed live-attenuated zoster vaccine (Zostavax) assessed in adults with hematologic malignancy. Betts:Merck: Research Funding. Wertheim:Merck: Research Funding. Zhao:Merck: Employment. Fernsler:Merck: Employment. Manoff:Merck: Employment. Annunziato:Merck: Employment.