Immunogenicity and safety of the adjuvanted recombinant zoster vaccine in patients with solid tumors, vaccinated before or during chemotherapy: A randomized trial

Abstract

; on behalf of the Zoster-028 Study Group BACKGROUND: The adjuvanted recombinant zoster vaccine (RZV) has demonstrated >90% efficacy against herpes zoster in adults ≥50 years of age and 68% efficacy in autologous hematopoietic stem cell transplant recipients ≥18 years of age. We report the immunogenicity and safety of RZV administered to patients with solid tumors (STs) before or at the start of a chemotherapy cycle. METHOD: In this phase 2/3 observer-blind, multicenter study (NCT01798056), patients with STs who were ≥18 years of age were randomized (1:1) to receive 2 doses of RZV or placebo 1-2 months apart and stratified (4:1) according to the timing of the first dose with respect to the start of a chemotherapy cycle (first vaccination 8-30 days before the start or at the start [±1 day] of a chemotherapy cycle). Anti-glycoprotein E (gE) antibody concentrations, gE-specific CD4 + T cell frequencies, and vaccine response rates (VRRs) were assessed 1 month after dose 1 and 1 and 12 months after dose 2. Reactogenicity and safety were assessed in the total vaccinated cohort through 12 months after dose 2. RESULTS: There were 232 participants in the total vaccinated cohort, 185 participants in the according-to-protocol cohort for humoral immunogenicity, and 58 participants in the according-to-protocol cohort for cell-mediated immunogenicity. Postvaccination anti-gE antibody concentrations, gE-specific CD4 + T cell frequencies and VRRs were higher in RZV recipients than in placebo recipients. Solicited adverse events (AEs) were more frequent among RZV recipients than placebo recipients. Incidence of unsolicited AEs, serious AEs, fatalities, and potential immune-mediated diseases were similar between RZV and placebo recipients. CONCLUSION: RZV was immunogenic in patients with STs receiving immunosuppressive chemotherapies. Humoral and cell-mediated immune responses persisted 1 year after vaccination. No safety concerns were identified.

Risk of herpes zoster in the Japanese population with immunocompromising and chronic disease conditions: Results from a claims database cohort study, from 2005 to 2014

“…Furthermore, in the context of our findings, as a recombinant vaccine, RZV has the potential for use in immunocompromised subjects in which live attenuated vaccines are contraindicated . The safety and immunogenicity of RZV immunization in immunocompromised subjects has been evaluated in a number of randomized studies (in patients undergoing HSCT, in patients with hematological or solid cancers, and in patients following renal transplantation) with no safety concerns . Although RZV is not approved for use in immunocompromised individuals aged less than 50 years, it is possible that future use in these patients could provide additional benefits to reduce the disease burden in those at greatest risk of HZ.…”

Immunization Strategies to Span the Spectrum of Immunocompromised Adults

“…Persons who received RZV before the start of chemotherapy had stronger humoral responses. 101 Persons who received RZV at both times had humoral immune responses that persisted 1 year after completion of the vaccine series. The extent of cell-mediated immune protection, which is postulated to be the main determinant of protection against herpes zoster infection in adults, warrants further evaluation, as this was only studied in a subgroup of participants and was found to be low.…”

“…The extent of cell-mediated immune protection, which is postulated to be the main determinant of protection against herpes zoster infection in adults, warrants further evaluation, as this was only studied in a subgroup of participants and was found to be low. 101 Efficacy studies are needed in the absence of clear immunologic correlates of protection. Further guidance from ACIP regarding the use of RZV in persons with malignancy is anticipated in the future.…”

<p>Varicella zoster virus vaccines: an update</p>

“…Although age is the most common risk factor for HZ, an increased incidence of HZ has also been associated with immunosuppression related to certain co-morbidities, such as solid tumors, hematological malignancies, HIV infection, autoimmune diseases and to immunosuppressive treatment. In these subjects the clinical picture can be atypical, more serious and has a longer duration 18…”

“…HZ is a major global health problem and incidence increases ≥50 years of age, due to the growing number of elderly, co-morbidity and/or immunosuppression 20. The incidence rate of HZ in cancers patients receiving immunosuppressive chemotherapy is estimated to be 3–4 times higher (12/1,000 person/year) than in the overall population 18…”