title: Safety and immunogenicity of inactivated varicella-zoster virus vaccine in adults with hematologic malignancies receiving treatment with anti-CD20 monoclonal antibodies.
abstract: Immunocompromised patients can experience significant morbidity and occasional mortality from complications associated with herpes zoster (HZ), but live attenuated HZ vaccine is contraindicated for these patients. Inactivated zoster vaccine (ZVIN) is in development for prevention of HZ in immunocompromised patients. However, there are limited data in the literature regarding the effect of anti-CD20 monoclonal antibodies on vaccine-related cell-mediated immune response. This study evaluated safety and immunogenicity of ZVINin patients with hematologic malignancies (HM) receiving anti-CD20 monoclonal antibodies (alone or in combination chemotherapy regimens) and not likely to undergo hematopoietic cell transplant (HCT) (n=80).
  
  
  
  This was an open-label, single-arm, multicenter Phase I study (NCT01460719) of a 4-dose ZVINregimen (∼30days between doses) in patients ⩾18years old. Blood samples were collected prior to dose 1 and 28days Postdose 4 to measure varicella zoster virus (VZV)-specific T-cell responses using interferon-γ enzyme-linked immunospot (IFN-γ ELISPOT). The primary hypothesis was that ZVINwould elicit significant VZV-specific immune responses at ∼28days Postdose 4, with a geometric fold rise (GMFR) >1.0. All vaccinated patients were evaluated for adverse events (AE) through 28days Postdose 4.
  
  
  
  ZVINelicited a statistically significant VZV-specific immune response measured by IFN-γ ELISPOT at 28days Postdose 4 (GMFR=4.34 [90% CI:3.01, 6.24], p-value<0.001), meeting the pre-specified success criterion. Overall, 85% (68/80) of patients reported ⩾1 AE, 44% (35/80) reported ⩾1 injection-site AE, and 74% (59/80) reported ⩾1 systemic AE. The majority of systemic AEs were non-serious and considered unrelated to vaccination by the investigator. Frequencies of AEs did not increase with subsequent doses of vaccine. No recipient of ZVINhad rash polymerase chain reaction (PCR) positive for VZV vaccine strain.
  
  
  
  In adults with HM receiving anti-CD20 monoclonal antibodies, ZVINwas well-tolerated and elicited statistically significant VZV-specific T-cell responses ∼28days Postdose 4. CLINICALTRIALS.GOV identifier: NCT01460719.
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Janie
authors.initials: J
authors.lastname: Parrino
authors.affiliation: Canadian Center for Vaccinology, IWK Health Centre and Nova Scotia Health Authority, Dalhousie University, Halifax, NS, Canada.
authors.forename: Shelly A
authors.initials: SA
authors.lastname: McNeil
authors.affiliation: Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Lawrence
authors.affiliation: Department of Medicine at Huddinge, Division of Hematology, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Kimby
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Marco F
authors.initials: MF
authors.lastname: Pagnoni
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Jon E
authors.initials: JE
authors.lastname: Stek
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Ivan S F
authors.initials: IS
authors.lastname: Chan
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA. Electronic address: susan_kaplan@merck.com.
authors.forename: Susan S
authors.initials: SS
authors.lastname: Kaplan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D019433:Chickenpox Vaccine / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D019337:Hematologic Neoplasms / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology*; D006562:Herpes Zoster / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D016867:Immunocompromised Host; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D000069283:Rituximab / Q000627:therapeutic use; D014611:Vaccination; D014613:Vaccines, Attenuated; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D019433:Chickenpox Vaccine; D014613:Vaccines, Attenuated; D000069283:Rituximab; D007371:Interferon-gamma
keywords: Herpes zoster; Immunogenicity; Safety; Tolerability; Zoster vaccine