After primary infection, varicella zoster virus establishes latency in sensory nerve ganglia.1 Reactivation of the virus can lead to herpes zoster, a typically unilateral, vesicular, dermatomal rash, usually accompanied by pain.2 The most common complication of herpes zoster, postherpetic neuralgia, can last for months or years.1, 3
Research in context
Evidence before this study
Adjuvanted recombinant zoster vaccine was highly immunogenic and more than 90% efficacious against herpes zoster in individuals aged 50 years and older. The adjuvanted recombinant zoster vaccine has also been reported to be immunogenic and well-tolerated in several immunocompromised populations, as well as efficacious against herpes zoster in autologous haemopoietic stem cell transplant recipients.
Added value of this study
This study assessed the adjuvanted recombinant zoster vaccine in patients with haematological malignancies who were receiving immunosuppressive treatments. The vaccine induced robust and persistent humoral and cell-mediated immune responses in our population of adults aged 18 years and older with various haematological malignancies. Cell-mediated immunity, considered to play a key part in protection against herpes zoster, was similar to that observed in otherwise generally healthy adults aged 50 years and older.
Implications of all the available evidence
Taken together with results of previous clinical trials, the results of our study show that the adjuvanted recombinant zoster vaccine is immunogenic in populations that are at an increased risk of herpes zoster infection, either due to older age or because of underlying conditions and their associated immunosuppressive treatments. This immunocompromised adult population is likely to benefit from vaccination with the adjuvanted recombinant zoster vaccine, which is licensed in Australia, Canada, Japan, USA, China, and the EU for adults aged 50 years and older.
The risk of herpes zoster increases with age, particularly after age 50 years, because of waning cell-mediated immunity.1 Immunocompromised people, particularly those with impaired cell-mediated immunity due to either underlying disease or immunosuppressive therapies,4, 5, 6, 7, 8, 9 are also at an increased risk of herpes zoster. The incidence of herpes zoster in individuals with haematological malignancies receiving immunosuppressive cancer treatments is up to ten times higher than in the overall population (31 per 1000 person-years vs 3·2 per 1000 person-years).3, 10 Herpes zoster occurs in up to a quarter of patients with multiple myeloma,11, 12, 13, 14 Hodgkin lymphoma,4, 15, 16 and chronic lymphocytic leukaemia,6, 7, 16 and in more than 6% of patients with non-Hodgkin lymphoma receiving immunosuppressive cancer treatments.15
Vaccination is an effective approach in the prevention of infectious diseases. Two vaccines are approved for prevention of herpes zoster in adults aged 50 years and older—the live-attenuated varicella zoster virus vaccine (Zostavax; Merck Sharp & Dohme Corp) and the adjuvanted recombinant zoster vaccine (Shingrix; GlaxoSmithKline Biologicals SA).
Zostavax is a live virus vaccine and is contraindicated in people with immunodeficiency due to malignancy or immunosuppressive therapy because of potential virulence in those with substantially impaired immunity.17, 18, 19, 20
Although usually not as immunogenic as live vaccines, inactivated vaccines can be used in immunocompromised populations.17, 18 An investigational inactivated varicella zoster vaccine administered on a four-dose schedule has been shown to be generally safe, immunogenic, and efficacious in autologous haematopoietic stem cell transplant recipients and patients with solid tumour malignancies receiving chemotherapy.21, 22, 23 However, this vaccine was not found to be efficacious in patients with haematological malignancies and evaluation of efficacy in this group was terminated early because of evidence of futility.23
Shingrix is an adjuvanted non-live subunit vaccine, consisting of the truncated form of varicella zoster virus glycoprotein E and the AS01B adjuvant system. This vaccine was highly immunogenic and more than 90% efficacious against herpes zoster in individuals older than 50 years.24, 25, 26 Shingrix was also immunogenic in immunocompromised populations aged 18 years and older, including in autologous haemopoietic stem cell transplant recipients, renal transplant recipients, patients with solid tumours, and people with HIV.27, 28, 29, 30, 31, 32 Two doses of Shingrix showed 68% efficacy in preventing herpes zoster in patients who had undergone autologous haemopoietic stem cell transplantation.32 In this population, 873 (94·7%) of 922 Shingrix recipients completed the two-dose vaccination schedule.32
This study aimed to evaluate the immunogenicity and safety of two doses of the adjuvanted recombinant zoster vaccine (Shingrix) in adults aged 18 years and older with haematological malignancies who were undergoing or had just finished immunosuppressive cancer treatments.